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Stress failure of pulmonary capillaries as a mechanism for exercise induced pulmonary haemorrhage in the horse
Equine Veterinary Journal
Abstract
Exercise induced pulmonary haemorrhage (EIPH) is a serious problem in the Thoroughbred industry. The condition apparently occurs essentially in all Thoroughbreds in training but the mechanism has proved elusive. There is now strong evidence that the condition is caused by mechanical failure of the walls of the pulmonary capillaries when the pressure inside them rises to very high levels. It is well known that pulmonary capillaries have extremely thin walls to allow rapid exchange of respiratory gases across them. Recently we have shown that the wall stresses are very large when the capillary transmural pressure is raised, and in anesthetised rabbits, ultrastructural damage to the walls is seen at pressures of 40 mmHg and above. The incidence of stress failure is greatly increased at high lung volumes; and many of the ultrastructural changes are rapidly reversible when the capillary pressure is reduced. The principal forces acting on the capillary have been analysed. The strength of the thin part of the capillary wall can be attributed to the Type IV collagen in the extracellular matrix. The pulmonary vascular pressures of galloping Thoroughbreds reach very high levels. Mean pulmonary artery and left atrial pressures of up to 120 and 70 mmHg respectively have been directly measured with indwelling catheters. The reason for the high pulmonary vascular pressures is that these animals have been selectively bred over hundreds of years to run at great speeds over short distances and their maximal oxygen consumptions are very high. As a consequence, cardiac outputs are substantial, and the left ventricle needs very high filling pressures.(ABSTRACT TRUNCATED AT 250 WORDS)
... Stress failure of pulmonary capillaries is assumed to be a key event in EIPH pathogenesis. West et al. (38) described pulmonary capillary wall disruption in horses that had exercised on a treadmill and proposed that capillary rupture in exercising horses occurs as a result of high pulmonary capillary pressures (37), which are estimated to reach between 72 and 83 mmHg (18,20). Further support for this theory was provided when the threshold for breaking strength of equine pulmonary capillaries was exceeded at 75 mmHg transmural pressure (5). ...
... A combination of a generalized failure of small pulmonary veins to dilate and enhanced dilation of caudodorsal pulmonary arteries in particular would expose capillaries in the caudodorsal lung to the greatest intravascular pressures during exercise. Such a regional increase in intravascular pressures could result in increased capillary stress failure (37,38), extravasation of blood into the pulmonary interstitium and airways, and consequential pathologic changes of EIPH, including venous remodeling, hemosiderin accumulation, and fibrosis (40). We speculate that this sequence of events could explain, at least in part, the regional caudodorsal distribution of EIPH in the horse lung. ...
... If parasympathetic outflow contributes to basal maintenance of tone in small pulmonary arteries in a regiondependent manner, perhaps fulfilling the role of protecting capillaries from high flow rates in this region and then diminished parasympathetic activity during exercise (22) could result in reduced arterial tone, in the caudodorsal lung specifically. This, along with a possible attenuation of muscarinic-receptor mediated pulmonary venous dilation in the same region, could result in transmission of higher pressures to caudodorsal pulmonary capillaries compared with capillaries in other lung regions, perhaps contributing to stress failure of capillaries in this region (37,38) and, ultimately, region-specific EIPH pathologic changes (40). However, when extrapolating these data to in vivo conditions, it is noted that all vessels in these studies were precontracted, and responses of pulmonary vessels to acetylcholine can vary depending on whether vascular tone is present (2). ...
... A pesar de los importantes progresos alcanzados con respecto al conocimiento de la etiología y patogénesis de la HPIE, la evidencia que existe no es concluyente [40] . Actualmente se proponen varias hipótesis: 1) Inflamación crónica de las vías aéreas menores lo cual resulta en neovascularización bronquial [23, 24, 25]. ...
... Actualmente se proponen varias hipótesis: 1) Inflamación crónica de las vías aéreas menores lo cual resulta en neovascularización bronquial [23, 24, 25]. La neovascularización bronquial puede causar debilitamiento estructural de los vasos y alteración del flujo sanguíneo, 2) La ruptura inducida por estrés de los capilares pulmonares que resulta de un gasto cardiaco incrementado [40], y/o propiedades reológicas alteradas [5, 21, 37] , 3) Disfunción de las plaquetas lo cual conduce a una predisposición a la hemorragia pulmonar [13] , 4) Trauma mecánico del tejido pulmonar que resulta de las ondas de presión propagadas a través del cuerpo cuando los cascos golpean el suelo [30]. Se ha propuesto que existe una relación entre la fisiopatología de la HPIE y la hiperviscosidad de la sangre, por tal motivo, se piensa que la pentoxifilina, un inhibidor de la fosfodiesterasa , que incrementa la deformabilidad de los glóbulos rojos y disminuye la viscosidad de la sangre, tiene el potencial para reducir la severidad de la hemorragia pulmonar inducida por el ejercicio [8, 37, 39, 40]. ...
... La neovascularización bronquial puede causar debilitamiento estructural de los vasos y alteración del flujo sanguíneo, 2) La ruptura inducida por estrés de los capilares pulmonares que resulta de un gasto cardiaco incrementado [40], y/o propiedades reológicas alteradas [5, 21, 37] , 3) Disfunción de las plaquetas lo cual conduce a una predisposición a la hemorragia pulmonar [13] , 4) Trauma mecánico del tejido pulmonar que resulta de las ondas de presión propagadas a través del cuerpo cuando los cascos golpean el suelo [30]. Se ha propuesto que existe una relación entre la fisiopatología de la HPIE y la hiperviscosidad de la sangre, por tal motivo, se piensa que la pentoxifilina, un inhibidor de la fosfodiesterasa , que incrementa la deformabilidad de los glóbulos rojos y disminuye la viscosidad de la sangre, tiene el potencial para reducir la severidad de la hemorragia pulmonar inducida por el ejercicio [8, 37, 39, 40]. La pentoxifilina (1-[5-oxohexil]-3,7-dimetil-xantina) pertenece a la clase de la metilxantina y es un derivado de la teo- bromina [9, 20] . ...
The purpose of this investigation was to determine the efficacy of the pentoxifylline in the treatment of exercise-induced pulmonary hemorrhage (EIPH) in Thoroughbred racehorses. One hundred forty six (146) animals were randomly selected with ages between 3 and 8 years old, they were subjected to two intense exercises (14.6 ± 0.4 m/s) on distances of 1000 meters each, the horses were submitted to endoscopic evaluation of the respiratory tract, between 30 and 90 minutes after each exercise, the objective was to determine the presence of the EIPH and to characterize the intensity of the bleeding. Later, the group of animals which presented EIPH on both exercises was selected in random order as representative sample of bleeding racehorses. They were 40 equines divided in two groups, 20 animals (group I) received pentoxifylline (8.5 mg/kg, q 12 h, PO) for 7 days and 20 horses (group II) that did not receive treatment. Subsequently, the day after the end of the treatment, on each one of the horses (group I and II), a third endoscopic evaluation of the upper respiratory tract was performed, 30 to 90 minutes after an intense exercise on 1000 meters distance, in order to see the occurrence and severity of the EIPH. The analysis of the data demonstrated statistically. significant difference (P < 0.05) between the presence and intensity of the EIPH and the administration of the pentoxifylline. Eight (40%) of the pentoxifilline-treated animals showed not EIPH, 20 (100%) not treated horses had evidence of EIPH. It was determined that the occurrence of moderate, profuse and visible EIPH respectively was larger in the not treated animals. Therefore, the treatment with pentoxifylline helps to prevent or to diminish the EIPH.
... Despite a documented history of epistaxis in many equine racing breeds (Pfaff, 1950(Pfaff, , 1976Speirs et al., 1982;Gelberg et al., 1985), relatively little is understood about its genetic aetiology. However, evidence suggests that epistaxis manifests as a consequence of EIPH, a condition caused by pulmonary capillary stress failure (West and Mathieu-Costello, 1994). While this evidence may help to explain the pathogenesis of epistaxis, genetic and nongenetic factors leading to the development of this condition are not fully understood. ...
... Our knowledge to date suggests that the aetiology of epistaxis is likely to be highly complex, requiring a specific combination of factors to be present for the condition to be expressed (Cook, 1974;West and Mathieu-Costello, 1994;Takahashi et al., 2001;Weideman et al., 2003Weideman et al., , 2004Hinchcliff et al., 2005;Newton et al., 2005;Langford et al., 2013). However, results from previous studies examining the role of non-genetic factors such as age, track condition and season of year are not uniform and strongly suggest the presence of genetic factors in the expression of epistaxis (Takahashi et al., 2001;Weideman et al., 2003;Hinchcliff et al., 2005;Newton et al., 2005;Langford et al., 2013). ...
... Although past research exploring the aetiology of epistaxis has yielded valuable insight into non-genetic factors influencing all grades of EIPH (Cook, 1974;West and Mathieu-Costello, 1994;Takahashi et al., 2001;Weideman et al., 2003Weideman et al., , 2004Hinchcliff et al., 2005;Newton et al., 2005;Langford et al., 2013), a consensus as to the role a horse's genetics play on epistaxis susceptibility has yet to be achieved. Using one of the largest Thoroughbred racing populations in the world, we were able to demonstrate that a significant proportion of the variation in epistaxis phenotype is attributable to the additive genetic variation in the population (h 2 = 0.27 and 0.50). ...
Post exercise epistaxis, the manifestation of a severe form of exercise-induced pulmonary haemorrhage (EIPH), has been observed in many equine racing populations. Although multiple analyses have suggested that non-genetic factors may lead to the development of this condition, relatively little consensus has been reached regarding its genetic aetiology. The objective of this study was to provide insight into both genetic and non-genetic factors that may contribute to the expression of epistaxis in the Australian Thoroughbred racing population. Racing records and reported epistaxis occurrences were acquired for 117,088 horses entered in races and official barrier trials from 1 August 2000 until 22 February 2011.
Heritability was estimated using two different logistic generalized linear mixed models (lifetime epistaxis risk h2 = 0.27 and individual race epistaxis risk h2 = 0.50). Sex, age, and year of birth were shown to be significant; however, trainer, jockey, race distance, condition of the track (i.e. ‘going’), racecourse, track surface, number of race starters, year and month of race were not significant. Evidence suggests genetic and non-genetic links to EIPH expressed as epistaxis.
... This in turn may result in stress failure of the mucosal capillaries and of the alveolar-capillary membrane. 5,6 The factors associated with petechiae formation and tracheobronchial bleeding in this setting have not been clearly elucidated. We think that some understanding may be extrapolated from the forensic literature on asphyxia. ...
... 16 Decades of research have shown that EIPH results when the transmural pressure, the difference between intracapillary and intra-alveolar pressures, overwhelms the tensile strength of the capillary wall, leading to the rupture of the alveolarcapillary membrane. 5,6 This capillary "stress failure" is thought to primarily result from high transmural pressure generated with vigorous inspiration. In an attempt to prevent EIPH, > 90% of North American racehorses are given furosemide before competing. ...
Negative pressure pulmonary edema is a well-described complication of upper airway obstruction. However, the simultaneous occurrence of blood-stained secretions and petechial tracheobronchial hemorrhage are rarely recognized and a potential complication of transient intentional occlusion of the airways. We described a case of "hemorrhagic bronchial mucosa syndrome" and asymptomatic blood-tinged pulmonary edema after balloon bronchoplasty for a concentric tracheal stenosis using a flexible bronchoscopy. This was characterized by interval appearance of diffuse petechial tracheobronchial bleeding and a persistent blood-tinged alveolar effluent after sustained occlusion of the airway. The simultaneous occurrence of both phenomena in this patient suggests different degrees of injury in a common pathogenic spectrum. We postulate that sustained, complete occlusion of the airway produces variable degrees of mechanical disruption of the bronchial and alveolar vasculature that lead to the development of negative pressure pulmonary edema and tracheobronchial hemorrhage. In this case, the syndrome was self-limited and without major consequences but highlights an unrecognized potential complication of balloon bronchoplasty.
... The phenomenon of exercise-induced hemoptysis is well known to occur in thoroughbred racehorses, but it is still relatively underrecognised or reported in human subjects [1,2]. However, in humans, still relatively very rare, there are occasional reports of exercise induced pulmonary hemorrhage or exercise-induced pulmonary oedema in the literature, specially occurring in marathon runners, cyclists and swimmers, and breath-hold divers [2,3]. ...
... We described a rare phenomenon in humans that has been well recognised in thoroughbred horses in the past [1]. There are now few reports of exercise-induced pulmonary hemorrhage or exercise-induced pulmonary oedema as we start to acknowledge the vulnerability of pulmonary capillaries to stress or mechanical failure during strenuous exercise and high cardiorespiratory workload [2,3]. ...
The phenomenon of exercise-induced hemoptysis is still relatively underrecognised in humans. We report a case of recurrent hemoptysis brought on by vigorous exercise. A 33-year-old male presented with several episodes of intermittent fresh small-volume hemoptysis reproducible on vigorous exercise. There was no other significant medical history other than a past history of testicular tumor, treated with orchidectomy and adjuvant Bleomycin-based chemotherapy 1 year prior to onset of symptoms. Computed tomography scan showed no major abnormalities other than few small bilateral non-specific nodules. Computed tomography aortogram and pulmonary angiogram, ventilation/perfusion scan, and echocardiography yielded no significant abnormalities. Infectious, autoimmune disease, coagulopathy, vasculitis, and malignant causes were excluded. Bronchoscopy showed possible endobronchial bleeding. This phenomenon is thought to be due to vulnerability of pulmonary capillaries to stress or mechanical failure during strenuous exercise at high cardiorespiratory workload.
... 8 This study population was examined following training only, and therefore the lower prevalence might be explained by differences in exercise intensity. 16 Cytological methods of EIPH diagnosis frequently result in higher prevalence estimates than observation of epistaxis or blood on tracheobronchoscopy. 1,6 In the current study, the 36% samplelevel prevalence of significant haemosiderophages in TW fluid was markedly higher than the 7% prevalence of tracheal blood. Similar findings have been reported in horses in flat training, with a 51% prevalence of increased haemosiderophages and 4% prevalence of tracheal blood. ...
Background
Exercise induced pulmonary haemorrhage (EIPH) is an important condition of horses performing high intensity exercise, with reported prevalence among racehorses of up to 95%, based on the detection of blood on tracheobronchoscopy. Previously identified risk factors include age, sex, season, race type, years spent in racing and lower airway inflammation.
Objectives
To estimate the prevalence of EIPH in British National Hunt racehorses as indicated by two outcome measures: presence of tracheal blood on tracheobronchoscopy, and presence of moderate‐large (significant) proportions of haemosiderophages in tracheal wash (TW) fluid; and to identify training‐related risk factors for these indicators of EIPH.
Study design
Prospective longitudinal study.
Methods
Data from tracheobronchoscopy and TW cytology were analysed using univariable and multivariable mixed‐effects logistic regression.
Results
1184 observations, from 177 horses, were analysed. The prevalence of tracheal blood was 7.2% (95%CI: 5.8, 8.8) and significant haemosiderophages in TW fluid was 36% (95%CI: 33.3, 38.8). Increased time in training was significantly associated with increased odds of EIPH. For each additional year spent in training the odds of tracheal blood and presence of significant proportions haemosiderophages increased approximately 1.5‐fold (OR = 1.5; 95%CI: 1.1‐2.0; P = .005; and OR = 1.5; 95%CI: 1.3, 1.8; P < .001, respectively). Current inflammation was associated with previous haemorrhage, but not current haemorrhage.
Main limitations
There are no standardised measures for quantification of TW cytological parameters for EIPH diagnosis. Few horses were examined following jumping. Recent racing dates were not included in analysis.
Conclusions
Increasing time in training was a risk factor for both indicators of EIPH. Current inflammation was associated with previous haemorrhage, but not current or future haemorrhage, suggesting that haemorrhage leads to inflammation but not that inflammation leads to haemorrhage. Overall, our findings are consistent with the capillary stress failure theory of EIPH. The development of standardised measures for TW cytological diagnosis of EIPH is warranted.
... West et Mathieu-Costello (1995) ont suggéré que le mécanisme de « stress failure » serait la cause de la formation d'un oedème pulmonaire interstitiel à l'exercice, notamment via l'augmentation de la pression artérielle pulmonaire (Pap) ). Cette théorie a été, dans un premier temps mise en avant chez le cheval pour comprendre les hémorragies pulmonaires observées chez les chevaux de course (West and Mathieu-Costello 1994). Il est estimé qu'une pression capillaire supérieure à 25 mmHg dans les capillaires pulmonaires est suffisante pour le développement de « stress failure », or chez l'athlètes entraînés en endurance, la Pap peut atteindre des valeurs de 40 mmHg, entraînant une Pcap de 25 mmHg Prefaut et al. 2000). ...
L’hypoxémie induite à l’exercice (HIE) est un phénomène qui est caractérisé par une chute de pression et de saturation artérielle en oxygène. La HIE touche les athlètes d'endurance. A force d’entrainement, les limites des systèmes cardiaque et musculaire sont repoussées et celles du système pulmonaire apparaissent. La prévalence de la HIE est de plus de 70% chez les athlètes lors d’un effort de course à pied. Or, les athlètes d’endurance sont les plus susceptibles de performer en altitude que ce soit dans le cadre d’une compétition, d’une préparation ou d’un stage d’entrainement. La chute de la pression atmosphérique rencontrée lors de l’élévation de l’altitude entraine une diminution de la quantité d’oxygène dans l’organisme qui constitue un vrai stress, le stress hypoxique. Pour faire face à ce dernier, l’organisme met en place une série d’adaptations visant à maintenir un apport en oxygène suffisant pour les organes. Lors d’un exercice au niveau de la mer les athlètes HIE atteignent les mêmes consommations maximales d’oxygène que les non-HIE, en revanche l’environnement délétère pour la performance que représente l’altitude, pourrait avoir de plus lourdes conséquences sur les athlètes HIE. Les effets de la HIE et de l’altitude pourraient se potentialiser et accroitre la réduction de la disponibilité de l’oxygène dans l’organisme. L’objectif de ce projet est de tester l’hypothèse que les réponses à l’exercice au niveau de la mer et en altitude sont différentes entre des athlètes HIE et non-HIE. Pour cela nous avons étudié les réponses à l’exercice en normoxie et après une exposition à l’altitude modérée aiguë (de quelques minutes à quelques heures) et prolongée (après 5 jours). La première étude montre une augmentation de la désoxygénation cérébrale et une diminution de l’oxygénation musculaire lors de l’exercice en normoxie, ainsi qu’une inadaptation lors de l’effort en hypoxie aiguë aux niveaux musculaire et cérébral. Les études 2 et 3 rapportent des réponses spécifiques à l’exercice, mais également au repos, lors des cinq premiers jours d’exposition en altitude. En effet, dès le repos les athlètes HIE ont des saturations en oxygène plus basses que les athlètes contrôles. Malgré la persistance de la HIE, des mécanismes compensatoires semblent être mis en place aux niveaux cérébral et cardiaque, éventuellement médiés par une balance pro-antioxydant différente. Ces derniers permettent l’atteinte de performances similaires au groupe contrôle après 1 et 5 jours d’exposition. L’étude 4 montre que la viscosité sanguine et l’hémodynamique pulmonaire ne sont pas impliquées dans la chute de saturation de repos plus prononcée des athlètes EIH au cours de l’exposition en altitude. L’étude 5 semble indiquer une réponse vasodilatatrice spécifique chez les athlètes HIE au niveau de la mer et après 5 jours en altitude. Il ressort de ce travail de thèse que la HIE réduit la performance en hypoxie aiguë et entraine des réponses spécifiques à l’exercice en normoxie et en hypoxie, sans doute dans le but de contrebalancer la chute de saturation en oxygène. Il est donc primordial de prendre en compte ce phénomène pour la performance en hypoxie, et d’étudier et comprendre ses interactions avec les différentes modalités d’entrainement, notamment en altitude.
... Exercise-induced pulmonary haemorrhage (EIPH) is frequently identified in horses performing high-intensity athletic activity. During exercise the pressure in the pulmonary capillaries reaches at least 80 mmHg [1], which is sufficient to cause pulmonary capillary stress failure [2,3]. Additionally, high transmural pressure (difference between the positive intraluminal and negative alveolar pressures) causes rupture of the blood-gas barrier [4]. ...
Exercise-induced pulmonary haemorrhage (EIPH) occurs in horses performing high-intensity athletic activity. The application of physics principles to derive a ‘physical model’, which is coherent with existing physiology and cell biology data, shows that critical parameters for capillary rupture are cell–cell adhesion and cell stiffness (cytoskeleton organisation). Specifically, length of fracture in the capillary is a ratio between the energy involved in cell–cell adhesion and the stiffness of cells suggesting that if the adhesion diminishes and/or that the stiffness of cells increases EIPH is more likely to occur. To identify genes associated with relevant cellular or physiological phenotypes, the physical model was used in a post-genome-wide association study (GWAS) to define gene sets associated with the model parameters. The primary study was a GWAS of EIPH where the phenotype was based on weekly tracheal wash samples collected over a two-year period from 72 horses in a flat race training yard. The EIPH phenotype was determined from cytological analysis of the tracheal wash samples, by scoring for the presence of red blood cells and haemosiderophages. Genotyping was performed using the Illumina Equine SNP50 BeadChip and analysed using linear regression in PLINK. Genes within significant genome regions were selected for sets based on their GeneOntology biological process, and analysed using fastBAT. The gene set analysis showed that genes associated with cell stiffness (cytoskeleton organisation) and blood flow have the most significant impact on EIPH risk.
... Studies have been carried out to investigate the causeeffect relationship between IAD and EIPH [22], and they describe two mechanisms: inflammation (and consequently bronchoconstriction), which increases intrapleural pressure and leads to bleeding, and the presence of blood in the alveoli and interstitial spaces, which may lead to inflammation and fibrosis [32]. However, EIPH can occur regardless of whether or not the pulmonary inflammation is present [34,35]. The association between EIPH and airway inflammation has been studied in race animals [1,12,15,26] but the results remain controversial. ...
The respiratory system is essential for health and high athletic performance in horses. Respiratory diseases have been recognized as having a major impact on training equine animals and are commonly cited as the second most common cause of wasted training time. Inflammatory airway disease (IAD) is an important cause of poor performance in young racehorses. Exercise-induced pulmonary hemorrhage (EIPH) is considered a major issue for the equine industry because of its high prevalence and association with reduced athletic performance. In Brazil, polo is a growing equestrian sport, but studies on it are still scarce. The aim of this study was to evaluate the occurrence of EIPH, the association between EIPH and IAD, and EIPH influence on the tracheal cytological profile of polo ponies. Thirty-seven horses regularly used for polo were included in this study. Endoscopic examination was performed every 30 to 90 min after practice, and tracheal lavage was performed after 18 to 24 hr. Sixteen animals (43.2%) presented a score of 0 for mucus in endoscopy; twelve animals (32.4%) presented a score for 1 and nine animals (24.3%) presented score 2 of mucus. IAD was characterized by tracheal cytology in 12 animals (32.4%). The occurrence of EIPH in this study was 29.7% (11/37). No significant difference was found in the cell types in tracheal cytology when EIPH-positive and EIPH-negative horses were compared. Polo ponies are affected by IAD and EIPH in relevant proportions, but there was no association between EIPH and tracheal cytological profile.
... 23 Among the factors thought to contribute to EIPH are high pulmonary vascular pressure exacerbated by a negative pleural pressure as respiratory effort and rate increase during intense exercise. 24,25 This high transmural pressure could lead to stress failure of the pulmonary capillaries causing blood to enter the airways and be seen endoscopically. 26 There was a weak positive correlation between the average speed and the presence of EIPH in this study; performance at higher speed has an effect on the likelihood of exhibiting EIPH in barrel racing horses. ...
Background:
Poor performance is often suspected to be associated with EIPH in barrel racing horses; however, there are no published reports of EIPH for this discipline. The prevalence of EIPH in barrel racing horses is also unknown.
Objectives:
This study was performed to determine the prevalence of EIPH and signs of airway inflammation in barrel racing horses under normal racing conditions in Alberta.
Animals:
About 170 barrel racing horses.
Methods:
Observational cross-sectional study. Tracheobronchoscopic examinations were performed at least 30 minutes postrace. Video recordings were scored off-site independently by two observers for EIPH and tracheal mucus accumulation (TMA). Horses with an EIPH score ≥2 were not assessed for TMA. Interobserver agreement was calculated by weighted κ statistics. Run times, environmental variables, and clinical information were also recorded for analysis.
Results:
77/170 (45.3%) of horses examined showed evidence of EIPH (grade ≥ 1). Interobserver agreement was 0.94. 140/141 (99.3%) of horses assessed for TMA showed evidence of tracheal mucus accumulation (grade ≥ 1) with 104/141 (73.8%) having a TMA score ≥ 2. Interobserver agreement was 0.73. A weak positive association was found between EIPH scores and average run speed, the presence of cough at rest reported by the riders, increased recovery time, exercise intolerance, and outdoor pattern.
Conclusions and clinical importance:
The high prevalence of EIPH observed in the sampled population indicates that barrel racing induces substantial stress on the lungs. The presence of EIPH did not impact negatively on performance. Factors such as environmental dust and frequent traveling might have contributed to the high prevalence of TMA observed.
... Considera-se, como evento fisiopatológico para a HPIE, a ruptura dos capilares pulmonares (falência pulmonar capilar) devido ao aumento da pressão transmural através do capilar, gerada tanto pelo aumento da pressão arterial pulmonar como pelas pressões pleurais bastante negativas (Holcombe, 2006). Contudo, apesar de aceitar-se que são requeridas pressões elevadas para que ocorra a falência dos capilares pulmonares (West eMathieu-Costello, 1994), cavalos que realizaram exercício submáximo também apresentaram HPIE (Epp et al., 2006;Viccino, 2007), constituindo um dilema para o entendimento da fisiopatologia da HPIE (West, 2000). Vários métodos para o diagnóstico da HPIE são sugeridos. ...
The present study evaluated the occurrence of exercise-induced pulmonary hemorrhage (EIPH) in jumping horses of 1.00 m-1.20 m. Seven horses were evaluated three times. Two of the evaluations were performed with airwayendoscopy 60 minutes after the second day of competition. Following endoscopy, animals were sedated for the collection of bronchoalveolar lavage (BAL) fluid, instilling 300 mL of sterile saline prewarmed at 37°C and immediately aspirated. The samples were centrifuged, the cell pellet was used for total nucleated cell count (TNCC), total erythrocyte count and differential cytology. The third evaluation was performed after 50 days of rest following competitions. Presence of blood in the tracheal lumen was graded 0 to 4. Epistaxis was not observed in the evaluated horses. One animal showed grade 1 of EIPH. BAL fluid TNCC was higher in the second evaluation in comparison with the first one (83.0 ± 34.8 vs. 55.0 ± 24.5 cells/μL BAL fluid, p = 0.017), reducing after 50 days of rest (15.5 ± 9.1 vs. 83.0 ± 34.8 cells/μL BAL fluid, p = 0.003). In the BAL differential cytology proceeded after 50 days of rest, there was a higher percentage of neutrophils in comparison with the first (25.9 ± 5.6% vs.17.7 ± 4.3%, p = 0.033) and second (25.9 ± 5.6% vs.7.6 ± 7.4%, p = 0.005) evaluations, indicating pulmonary inflammation after the period of competition. This was associated with EIPH, evidenced by the increased number of erythrocytes in BAL fluid of the second evaluation in comparison with the first (5.2 ± 3.1 vs. 0.9 ± 0.4 erythrocytes/μL BAL fluid, p = 0.048) and increased percentage of hemosiderophages after 50 days of rest (p = 0.032). It was concluded that horses performing submaximal exercise are prone to EIPH and it is associated with pulmonary inflammation.
... Moreover, trauma to the lung parenchyma, especially when it involves compression of the lung by the diaphragm that has been displaced by the abdominal contents, leads to temporary expansion of the alveoli during galloping. This trauma can destroy epithelial and endothelial cells (West and Mathieu-Costello 1994. The role of the diaphragm and other muscles in the horse's breathing has been widely discussed, particularly in relation to whether the action of the diaphragm is a passive or active movement acting against or in conjunction with the abdominal contents. ...
Exercise-induced pulmonary haemorrhage is a major cause of poor performance in the equine athlete. It is an important cause of exercise intolerance and results from strenuous exercise and pathophysiological changes in the equine lung and possibly in the airways. Endoscopic surveys of the respiratory tracts of horses after competitive events have shown that many horses experience exercise-induced pulmonary haemorrhage. The reported incidence of exercise-induced pulmonary haemorrhage in different breeds varies between 40-85%. The cause of bleeding in exercising horses has fostered considerable debate over the past three centuries, but currently, the most accepted hypothesis is that the source of haemorrhage is disruption of the pulmonary capillaries during exercise. Furosemide is the medication used most widely for the treatment and prevention of exercise-induced pulmonary haemorrhage. This review provides an update on the aetiology, clinical signs, physiopathology, diagnosis and treatment of exercise-induced pulmonary haemorrhage.
... These breaks increased proportionally to the rise in pressure and fell as the pressure in the pulmonary capillaries was reduced, indicating rapid reversibility of these ultrastructure changes [9]. West and colleagues similarly showed evidence of disruption of pulmonary capillaries in three thoroughbred horses made to gallop on a treadmill [10]. Poor performance in racehorses attributed to EIPH improves with diuretic therapy [3, 11], suggesting that reduction in pulmonary pressures has a protective effect. ...
The integrity of the pulmonary blood-gas barrier is vulnerable to intense exercise in elite athletes, similar to the phenomenon of exercise-induced pulmonary hemorrhage in thoroughbred racehorses. A 50-year-old previously healthy man presented with acute onset shortness of breath, dry cough, and hypoxemia after engaging in an extremely vigorous game of handball. CT scan of the chest showed diffuse patchy air-space disease. Bronchoalveolar lavage revealed diffuse alveolar hemorrhage. Infectious etiologies and bleeding diatheses were excluded by laboratory testing. Serological tests for ANCA-associated vasculitis, lupus, and Goodpasture's disease also were negative. A transthoracic echocardiogram was normal. The patient recovered completely on supportive therapy in less than 72 h. This case demonstrates strenuous exercise as a cause of diffuse alveolar hemorrhage in a previously healthy male with no apparent underlying cardiopulmonary disease.
... Multiple hypotheses have been proposed, but complex interactions are most likely to be responsible. Accumulated evidence indicates that EIPH results from the disruption of pulmonary alveolar capillary walls during exercise and only occasionally stems from bronchial capillaries [174][175][176]. Although the equine alveolocapillary wall is more resistant to shear forces than that of certain other species [177], its disruption is promoted during exertion by the occurrence of remarkable transmural pressures, beyond the rupture threshold of 75-100 mmHg [178,179]. ...
Given that aerobic metabolism is the predominant energy pathway for most sports, the respiratory system can be a rate-limiting factor in the exercise capacity of fit and healthy horses. Consequently, respiratory diseases, even in mild forms, are potentially deleterious to any athletic performance. The functional impairment associated with a respiratory condition depends on the degree of severity of the disease and the equestrian discipline involved. Respiratory abnormalities generally result in an increase in respiratory impedance and work of breathing and a reduced level of ventilation that can be detected objectively by deterioration in breathing mechanics and arterial blood gas tensions and/or lactataemia. The overall prevalence of airway diseases is comparatively high in equine athletes and may affect the upper airways, lower airways or both. Diseases of the airways have been associated with a wide variety of anatomical and/or inflammatory conditions. In some instances, the diagnosis is challenging because conditions can be subclinical in horses at rest and become clinically relevant only during exercise. In such cases, an exercise test may be warranted in the evaluation of the patient. The design of the exercise test is critical to inducing the clinical signs of the problem and establishing an accurate diagnosis. Additional diagnostic techniques, such as airway sampling, can be valuable in the diagnosis of subclinical lower airway problems that have the capacity to impair performance. As all these techniques become more widely used in practice, they should inevitably enhance veterinarians' diagnostic capabilities and improve their assessment of treatment effectiveness and the long-term management of equine athletes.
... Multiple hypotheses have been proposed, but complex interactions are most likely to be responsible. Accumulated evidence indicates that EIPH results from the disruption of pulmonary alveolar capillary walls during exercise and only occasionally stems from bronchial capillaries [174][175][176]. Although the equine alveolocapillary wall is more resistant to shear forces than that of certain other species [177], its disruption is promoted during exertion by the occurrence of remarkable transmural pressures, beyond the rupture threshold of 75-100 mmHg [178,179]. ...
Horses are elite athletes when compared with other mammalian species. In the latter, performance is limited by cardiovascular or musculoskeletal performance whereas in athletic horses it is the respiratory system that appears to be rate limiting and virtually all horses exercising at high intensities become hypoxaemic and hypercapnoeic. This is due to both diffusion limitation and a level of ventilation inadequate for the metabolic level that enables horses to exercise at these intensities. In conjunction with these blood gas changes, total pulmonary resistance increases and the work of breathing rises exponentially and airflow eventually plateaus despite increases in inspiratory and expiratory intrapleural pressures. Horses breathe at comparatively high frequencies when galloping due to the tight 1:1 coupling of strides to breathing. Whether this effects gas exchange and, if so, to what extent, has not been fully elucidated.
... EIPH originates mainly from the dorsocaudal region of the diaphragmatic lobes of the equine lung as a consequence of strenuous exercise. The mechanism of EIPH is unknown, but one theory is that haemorrhage is the result of stress failure of pulmonary capillaries (the combination of a relatively thin blood gas barrier required to support a high maximal oxygen uptake, and the high pulmonary capillary transmural pressures as a result of both high vascular and very negative alveolar pressures, places a tremendous stress on the pulmonary capillary walls) (West et al. 1993). Schroter et al. (1998Schroter et al. ( , 1999 suggested an alternative mechanism of pulmonary capillary disruption, due to localised shear stress within the pulmonary tissue resulting from loading (compression) of the chest by the forelimbs. ...
Epistaxis is a clinical sign which occurs with a wide range of disorders of the equine upper and lower respiratory tract. The nature of the epistaxis and the presence of concurrent clinical signs may give clues as to the site and cause of haemorrhage. Unilateral epistaxis usually indicates that the lesion is located in the upper respiratory tract, whereas bilateral epistaxis usually originates from the lower respiratory tract or the guttural pouches (if large volumes of haemorrhage are involved). Endoscopic examination of the respiratory tract often results in a definitive diagnosis, but if not, will usually reveal the anatomical location of the source of haemorrhage. Radiography is often useful for evaluation of the extent and nature of lesions which are not visualised or incompletely visualised using endoscopy. Other imaging modalities can be useful in selected cases. The most common causes of epistaxis occurring at rest are facial and sinonasal trauma, progressive ethmoidal haematomas and guttural pouch mycosis. In horses which have recently undergone fast exercise, exercise-induced pulmonary haemorrhage is the most likely cause of epistaxis.
The gas exchange function of the avian respiratory system is explained. The following important structural—and functional aspects are presented: the mechanisms of airflow through the airway (bronchial) system and the air sacs; the four-phase respiratory modus operandi of the avian respiratory system and the inspiratory and the expiratory aerodynamic valving mechanisms by which air is shunted across the airways; the physiological adaptations of coping with hypoxia and hypocapnia, especially during high altitude residence and flight; the functional significance of the physical strength of the avian lung, the air and the blood capillaries and the blood-gas barrier; the gas exchange designs, namely, the countercurrent, the crosscurrent, and the multicapillary serial arterialization systems of the avian lung and; the morphometric specializations of phylogenetically different species of birds and those that lead various lifestyles. The exceptional functional efficiency of the avian respiratory system is highlighted.
Poor performance and gait deficits in the equine athlete are most commonly caused by lameness of orthopaedic origin; however, there are numerous other potential sources that should be taken into consideration. This review describes the clinical signs and diagnostic tests for non‐orthopaedic causes of poor performance and gait deficits in the equine athlete.
Background:
Exercise-induced pulmonary hemorrhage (EIPH) refers to bleeding from the lungs in association with strenuous exercise. It has been documented in race horses but little information exists on EIPH in barrel racing horses.
Hypothesis/objectives:
Our goals were to evaluate the presence of EIPH in barrel racing horses and estimate its prevalence in the Pacific Northwest.
Animals:
149 barrel racing horses enrolled at events in WA (11), ID (3), and MT (33).
Methods:
Observational cross-sectional study. Data collected included signalment, history of illness, respiratory disease, race division, and pre-race medications. Endoscopy was performed and tracheobronchoscopic (TBE) EIPH score was assigned based on quantity of blood in the trachea (0 = no blood to 4 = abundance of blood within the trachea). After TBE, bronchoalveolar lavage (BAL) was performed. Erythrocyte (red blood cell, RBC) counts were obtained from bronchoalveolar lavage fluid (BALF). Statistical analysis included linear and logistic regression, Fisher's exact t test, and calculation of correlation coefficient. Significance was set at P < .05.
Results:
The prevalence of EIPH based on TBE EIPH score was 54%. When based on BALF RBC count >1,000 cells, EIPH prevalence was 66%. Race time did not significantly affect the presence of EIPH. A significant (P < .0001) positive linear relationship between the TBE and BAL erythrocyte count was identified, but its strength was poor (r2 = .15).
Conclusions and clinical importance:
EIPH occurs in over 50% of barrel racing horses in the Pacific Northwest. Precise determination of the impact of EIPH on health of barrel racers requires further study.
David C Poole,1,2 Howard H Erickson1 1Department of Anatomy and Physiology, 2Department of Kinesiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA Abstract: As the Thoroughbreds race for the final stretch, 44 hooves flash and thunder creating a cacophony of tortured air and turf. Orchestrated by selective breeding for physiology and biomechanics, expressed as speed, the millennia-old symphony of man and beast reaches its climax. At nearly 73 kilometers per hour (45 mph) over half a ton of flesh and bone dwarfs its limpet-like jockey as, eyes wild and nostrils flaring, their necks stretch for glory. Beneath each resplendent livery-adorned, latherin-splattered coat hides a monstrous heart trilling at 4 beats per second, and each minute, driving over 400 L (105 gallons) of oxygen-rich blood from lungs to muscles. Matching breath to stride frequency, those lungs will inhale 16 L (4 gallons) of air each stride moving >1,000 L/min in and out of each nostril – and yet failing. Engorged with blood and stretched to breaking point, those lungs can no longer redden the arterial blood but leave it dusky and cyanotic. Their exquisitely thin blood–gas barrier, a mere 10.5 μm thick (1/50,000 of an inch), ruptures, and red cells invade the lungs. After the race is won and lost, long after the frenetic crowd has quieted and gone, that blood will clog and inflame the airways. For a few horses, those who bleed extensively, it will overflow their lungs and spray from their nostrils incarnadining the walls of their stall: a horrifically poignant canvas that strikes at horse racing’s very core. That exercise-induced pulmonary hemorrhage (EIPH) occurs is a medical and physiological reality. That every reasonable exigency is not taken to reduce/prevent it would be a travesty. This review is not intended to provide an exhaustive coverage of EIPH for which the reader is referred to recent reviews, rather, after a brief reminder of its physiologic and pathologic bases, focus is brought on the latest developments in EIPH discovery as this informs state-of-the-art knowledge, the implementation of that knowledge and recommendations for future research and treatment. Keywords: epistaxis, Thoroughbred racehorse, pulmonary capillary rupture, vascular pressure, alveolar pressure, nasal airway collapse
En plaine, la moitié des athlètes entrainés en endurance sont susceptibles de développer une hypoxémie induite par l’exercice (HIE). Actuellement, la pratique des sports d’endurance de montagne est en plein essor. Dans ces disciplines, les athlètes très entrainés en endurance et donc susceptibles de développer une HIE, évoluent régulièrement en altitude modérée. Ce travail s’est intéressé à l’évolution de la HIE en altitude modérée, ainsi qu’à ses conséquences et sa relation avec la modification des composantes cardio-respiratoires à l’exercice. Nos résultats indiquent que : 1) la désaturation artérielle n’est pas potentialisée en altitude aiguë chez les athlètes HIE par rapport à des athlètes non-HIE alors que les athlètes HIE ont une chute de consommation maximale d’oxygène et de fréquence cardiaque maximale plus importante, 2) les athlètes HIE développent un stress hémodynamique important associé à des réponses vasculaires pulmonaires spécifiques à l’exercice en plaine, 3) tous les athlètes présentent une limitation de la diffusion pulmonaire à l’exercice maximal en altitude aiguë et nos résultats ne permettent pas d’affirmer une limitation cardiaque plus importante chez les athlètes HIE, 4) en hypoxie chronique, la désaturation artérielle est influencée par les modalités de pratique sportive. Notre travail a permis d’établir des recommandations pour les athlètes entrainés en endurance, de plus en plus nombreux, désirant performer en altitude modérée.
Exercise-induced pulmonary hemorrhage (EIPH) is as mayor cause of poor performance in the equine athlete. It is an important cause of exercise intolerance and results from strenuous exercise and pathophysiological changes in the equine lung and possibly in the airways. Endoscopic surveys of the respiratory tract of horses after competitive events have shown that many horses experience EIPH, but only a relativity small percentage shows blood at the nostrils. The reported incidence of EIPH in different breeds varies between 40-85 percent. The cause of bleeding in exercising horses has had considerable debate over the past three centuries, but currently the most accepted hypothesis is that the source of hemorrhage is due to the lungs capillary disruption during exercise. This capillary disruption increases with increasing vascular transmural pressure during exercise. Many therapeutic regimens have been suggested; but there have been few studies performed to evaluate the efficacy of these treatments. Furosemide is the most widely used medication for the treatment and prevention of EIPH, due to its ability to attenuate the exercise induced increase in right atrial, pulmonary arterial and pulmonary capillary pressure. The hemodynamic effect of furosemide is mediated by a reduction in plasma and blood volume. The purpose of this review is to give an up-date on the etiology, clinical signs, physiophathology, diagnosis and treatment of EIPH.
Focusing on the horse, this practical text is the second in a series of three to focus on veterinary diagnostic imaging and the new technologies available to help diagnose and pinpoint disease. Like Veterinary Diagnostic Imaging: The Dog and Cat, Veterinary Diagnostic Imaging: The Horse is organized by region with specific structures addressed within each region. Coverage includes background information, normal anatomy, and positioning for specific structures, followed by imaging findings and specific problems such as trauma/fracture, infection and neoplasm. The main focus of this book is radiology, with supplementary information on ultrasound, CT, and MRI. Includes Radiographic Diagnostic Indicators (RDIs), a versatile set of potential radiographic observations that, when used in combination, can often lead to a radiographic diagnosis. Features normal radiographs pictured near abnormal images for comparison. Provides telescopic images that provide both orientation and close-up views to help readers identify key points of the radiograph. Offers diagnosis at a glance with concise one or two word diagnoses in bold within each legend for quick reference. Features Emphasis Zones that electronically enhance regions of interest in more complex images.
As extreme sports become more popular, related respiratory injury may compromise the athlete’s performance and result in morbidity and even mortality. In this article we will discuss different lung injuries in relation to performing different activities in an extreme environment.
The evolution of fish to amphibians, reptiles to endothermic birds and mammals has been accompanied by a progressively thinner pulmonary blood gas barrier, to accommodate the constraint of increased oxygen uptake and carbon dioxide output [1]. Accordingly, pulmonary circulation has evolved as a separate high flow–low pressure system. In humans, mean pulmonary artery pressures (PAP) are 8–20 mmHg, pulmonary wedge pressures are 5–14 mmHg and pulmonary capillary pressures are 8–12 mmHg [2]. A low-pressure regimen preserves the integrity of an alveolar capillary membrane only 0.3 μm thick. However, this structure is vulnerable to increased pressures during strenuous exercise or environmental hypoxic exposure as a cause of stress failure of the pulmonary capillaries and accumulation of extravascular lung water [3]. Reports of lung injury related to extremes of exercise and variations in ambient pressure and altitude confirm this vulnerability. The resulting lung injury takes the form of noncardiogenic pulmonary oedema.
The occurrence of noncardiogenic pulmonary oedema and pulmonary haemorrhage has been described in relation to a variety of disorders related to auto- and exogenous immunological reactions, infections and certain inhalants. However, numerous reports of lung injury manifesting as pulmonary oedema with associated haemorrhage have been described more recently in relation to immersion underwater, swimming, extreme exercise and exposure to altitude. In addition, pulmonary oedema resulting from negative intra-alveolar pressure has been described in the anaesthesia literature and may play a role in exercise- and immersion-induced pulmonary oedema.
A single mechanism responsible for production of noncardiogenic pulmonary oedema related to immersion, altitude and exercise has not …
The respiratory system is commonly divided into two sections, the upper respiratory tract (URT) and the lower respiratory tract (LRT). Beyond the anatomy of the respiratory system, drug-specific factors, including protein binding and tissue penetration, also affect the disposition of drugs to the lungs. There are two major presentations of bacterial infections in the lungs: juvenile bronchopneumonia and adult pneumonia/pleuropneumonia. One of the more time-honored drugs used to treat equine pneumonia is the beta-lactam ampicillin. The use of aerosolized antimicrobials to treat pulmonary infections is intuitively attractive. The most important treatment for viral infections is excellent supportive nursing care, ensuring that sick horses drink and eat sufficiently. Guttural pouch mycosis (GPM) is found in all breeds and ages of horses. The first goal in treatment of GPM must be to avoid fatal exsanguination due to erosion into one of the major arteries.
Exercise-induced pulmonary hemorrhage (EIPH) is an important disease of horses that perform high-intensity athletic activity. EIPH is an ongoing concern for the racing industry because of its high prevalence; potential impact on performance; welfare concerns; and use of prophylactic medications, such as furosemide, on race day. During the last 10 years, significant progress has been made in understanding the pathogenesis and risk factors for EIPH and the impact of the disease on performance and career. This article summarizes the most recent advances in EIPH.
Copyright © 2015 Elsevier Inc. All rights reserved.
The present study evaluated the occurrence of exercise-induced pulmonary hemorrhage (EIPH) in jumping horses of 1.00 m - 1.20 m. Seven horses were evaluated three times. Two of the evaluations were performed with airway endoscopy 60 minutes after the second day of competition. Following endoscopy, animals were sedated for the collection of bronchoalveolar lavage (BAL) fluid, instilling 300 mL of sterile saline prewarmed at 37ºC and immediately aspirated. The samples were centrifuged, the cell pellet was used for total nucleated cell count (TNCC), total erythrocyte count and differential cytology. The third evaluation was performed after 50 days of rest following competitions. Presence of blood in the tracheal lumen was graded 0 to 4. Epistaxis was not observed in the evaluated horses. One animal showed grade 1 of EIPH. BAL fluid TNCC was higher in the second evaluation in comparison with the first one (83.0 ± 34.8 vs. 55.0 ± 24.5 cells/μL BAL fluid, p = 0.017), reducing after 50 days of rest (15.5 ± 9.1 vs. 83.0 ± 34.8 cells/μL BAL fluid, p = 0.003). In the BAL differential cytology proceeded after 50 days of rest, there was a higher percentage of neutrophils in comparison with the first (25.9 ± 5.6% vs.17.7 ± 4.3%, p = 0.033) and second (25.9 ± 5.6% vs.7.6 ± 7.4%, p = 0.005) evaluations, indicating pulmonary inflammation after the period of competition. This was associated with EIPH, evidenced by the increased number of erythrocytes in BAL fluid of the second evaluation in comparison with the first (5.2 ± 3.1 vs. 0.9 ± 0.4 erythrocytes/μL BAL fluid, p = 0.048) and increased percentage of hemosiderophages after 50 days of rest (p = 0.032). It was concluded that horses performing submaximal exercise are prone to EIPH and it is associated with pulmonary inflammation.
Pedigree and race run data from Thoroughbreds racing in Southern Africa, covering the period 1986-2002 (63 146 horses in pedigree data-set and 778 532 race runs), were analysed in order to study genetic and environmental factors affecting the incidence of epistaxis as associated with "exercise-induced pulmonary haemorrhage" (EIPH). Variables that were tested as significant in preliminary data analyses were included as fixed effects for the model. Various combinations of such variables namely age, weight, altitude, sex, month and going were tested. Fixed effects that were included in the final model were gender, going and altitude. The heritability estimates from a logit transformed analysis for epistaxis fitting both the animal and sire models were 0.23 and 0.40, respectively, which indicated that epistaxis as associated with EIPH in Southern African Thoroughbred sires has a strong genetic basis. Genetic trends indicating an increase in epistaxis were also found. Affected stallions and those racing whilst being treated with furosemide should be barred from breeding and not be considered as future sires. Estimated breeding values for epistaxis should be used as a tool for selecting against it and be considered in breeding programmes to decrease the incidence thereof.
Complete blood-gas barrier breaks (BGBBs) and epithelial-epithelial cells connections breaks (E-ECCBs) were enumerated in the lungs of free range chickens, Gallus gallus variant domesticus after vascular perfusion at different pressures. The E-ECCBs surpassed the BGBBs by a factor of ~2. This showed that the former parts of the gas exchange tissue were structurally weaker or more vulnerable to failure than the latter. The differences in the numbers of BGBBs and E-ECCBs in the different regions of the lung supplied with blood by the 4 main branches of the pulmonary artery (PA) corresponded with the diameters of the blood vessels, the angles at which they bifurcated from the PA, and the positions along the PA where they branched off. Most of the BGBBs and the E-ECCBs occurred in the regions supplied by the accessory- and the caudomedial branches: the former is the narrowest branch and the first blood vessel to separate from the PA while the latter is the most direct extension of the PA and is the widest. The E-ECCBs appeared to separate and fail from tensing of the blood capillary walls, as the perfusion- and intramural pressures increased. Compared to the mammalian lungs on which data are available, i.e., those of the rabbit, the dog, and the horse, the blood-gas barrier of the lung of free range chickens appears to be substantially stronger for its thinness.
We report five patients who presented to an on-site medical team with concurrent haemoptysis and shortness of breath at a recent triathlon event. After initial management in the field, three of the five patients were transported to hospital via ambulance for further management, resulting in patients with haemoptysis and dyspnoea being 17 times more likely to require hospital transport. It is important to consider the differential diagnoses for this presentation, particularly exercise-induced pulmonary oedema.
Exercise-induced pulmonary hemorrhage (EIPH) is as mayor cause of poor performance in the equine athlete. It is an important cause of exercise intolerance and results from strenuous exercise and pathophysiological changes in the equine lung and possibly in the airways. Endoscopic surveys of the respiratory tract of horses after competitive events have shown that many horses experience EIPH, but only a relativity small percentage shows blood at the nostrils. The reported incidence of EIPH in different breeds varies between 40-85 percent. The cause of bleeding in exercising horses has had considerable debate over the past three centuries, but currently the most accepted hypothesis is that the source of hemorrhage is due to the lungs capillary disruption during exercise. This capillary disruption increases with increasing vascular transmural pressure during exercise. Many therapeutic regimens have been suggested; but there have been few studies performed to evaluate the efficacy of these treatments. Furosemide is the most widely used medication for the treatment and prevention of EIPH, due to its ability to attenuate the exercise induced increase in right atrial, pulmonary arterial and pulmonary capillary pressure. The hemodynamic effect of furosemide is mediated by a reduction in plasma and blood volume. The purpose of this review is to give an up-date on the etiology, clinical signs, physiophathology, diagnosis and treatment of EIPH
During intense exercise, pulmonary capillary stress failure results in exercise-induced pulmonary hemorrhage (EIPH). To date, a principal focus has been the high pulmonary artery pressures (Ppa) manifest during high intensity exercise as one of the predominant mechanisms that elevates capillary transmural pressure resulting in rupture of the blood-gas barrier. However, it is possible that vascular pressures at other locations (e.g., venular) and extravascular pressures may also be important in the etiology of EIPH. To investigate further the relationship between EIPH and Ppa, five horses ran on an equine treadmill to volitional fatigue under control (CON) and nitric oxide synthase inhibition (L-NAME, 20 mg/kg, i.v.) conditions. Administration of L-NAME significantly increased EIPH (CON, 522.0 ± 453.8; L-NAME, 1178.7 ± 937.7 × 106 RBC/ml bronchoalveolar lavage fluid; p < 0.05) in all five horses despite reductions in Ppa and cardiac output () in four of the five horses. Within trials, Ppa was highly correlated with EIPH. However, across the range of Ppa's, the severity of EIPH was greater in the L-NAME run (p < 0.05). There was a significant positive relationship (r = 0.95, p < 0.05) between the change in maximal Ppa-to- ratio and the percentage change in EIPH between trials. These data suggest that events at other locations e.g., pulmonary venules and/or airways may be of great importance in regulating pulmonary capillary transmural pressure and inducing rupture of the blood-gas barrier.
Acute lung injury is a general term that describes injurious conditions that can range from mild interstitial edema to massive inflammatory tissue destruction. This review will cover theoretical considerations and quantitative and semi-quantitative methods for assessing edema formation and increased vascular permeability during lung injury. Pulmonary edema can be quantitated directly using gravimetric methods, or indirectly by descriptive microscopy, quantitative morphometric microscopy, altered lung mechanics, high-resolution computed tomography, magnetic resonance imaging, positron emission tomography, or x-ray films. Lung vascular permeability to fluid can be evaluated by measuring the filtration coefficient (Kf) and permeability to solutes evaluated from their blood to lung clearances. Albumin clearances can then be used to calculate specific permeability-surface area products (PS) and reflection coefficients (σ). These methods as applied to a wide variety of transgenic mice subjected to acute lung injury by hyperoxic exposure, sepsis, ischemia-reperfusion, acid aspiration, oleic acid infusion, repeated lung lavage, and bleomycin are reviewed. These commonly used animal models simulate features of the acute respiratory distress syndrome, and the preparation of genetically modified mice and their use for defining specific pathways in these disease models are outlined. Although the initiating events differ widely, many of the subsequent inflammatory processes causing lung injury and increased vascular permeability are surprisingly similar for many etiologies. © 2011 American Physiological Society. Compr Physiol 1:835-882, 2011.
The role of cardiac function or dysfunction in the pathogenesis of exercise-induced pulmonary hypertension and haemorrhage in horses has been minimally investigated. We hypothesize that pericardiotomy would enhance diastolic function and attenuate pulmonary vascular pressures in maximally exercising horses. Our objective was to evaluate diastolic function and cardiopulmonary pressures before and after pericardiotomy, at rest and at maximal exercise. Study design was both self- and externally controlled. Five horses underwent pericardiotomy after a baseline exercise test. They subsequently performed the same exercise protocol at 1 week and 13 weeks post-operatively. An external, unoperated control group of five horses performed the same experimental protocol. Pulmonary arterial pressure (PAP), pulmonary artery wedge pressure (PWP), right ventricular pressure, heart rate (HR) and oesophageal pressure were measured continuously at rest and at maximal exercise; maximum rates of ventricular pressure decrease (−dP/dtmax), relaxation half-time (t1/2), time constant of isovolumic relaxation (τ) and pulmonary capillary pressures (PcapP) were derived. Statistical analysis was performed using two-tailed Wilcoxon's signed-rank and rank-sum tests, with significance set at P<0.05. No significant differences were found in any variable after pericardiotomy was performed or between the experimental and external control groups. We conclude that during a 13-week study period, pericardiotomy does not alter pulmonary or ventricular pressures or rate of ventricular relaxation in the resting or maximally exercising horse. Results indicate that, in past and future studies requiring an open pericardium in normal horses, the cardiopulmonary parameters measured here are not affected by reduced pericardial pressure.
Major sporting events such as the Olympic Games highlight extraordinary human athletic achievements, performed by the extreme physical outliers of our species. However, there is a range of animal performance that goes far beyond these, both in the wild and in selectively bred 'sports animals' such as the racehorse, racing camel, greyhound, sled-dog and racing pigeon. In this selective review, Craig Sharp assesses how human beings measure up in the animal athletic stakes.
Apparently functionless, repetitive behaviour in horses, such as weaving or crib-biting has been difficult to explain for
behavioural scientists, horse owners and veterinarians alike. Traditionally activities such as these have been classed amongst
the broad descriptor of undesirable stable vices and treatment has centred on prevention of the behaviours per se rather than
addressing their underlying causes. In contrast, welfare scientists have described such activities as apparently abnormal
stereotypies, claiming they are indicative of poor welfare, citing negative emotions such as boredom, frustration or aversion
in the stable environment and even suggesting prevention of the activities alone can lead to increased distress. Our understanding
of equine stereotypies has advanced significantly in recent years with epidemiological, developmental and experimental studies
identifying those factors closely associated with the performance of stereotypies in stabled horses. These have allowed the
development of new treatments based on removing the causal factors, improving the horses’ social and nutritional environment,
re-training of horses and their owners and redirection of the activities to less harmful forms. Repetitive activities conventionally
seen as undesirable responses to the stable environment, their causal basis and the effectiveness of different approaches
to treatment are discussed, both in terms of reducing the behaviour and improving the horse’s quality of life.
The horse is a social species living in herds and spending the majority of its time roaming and foraging in a diverse and
seasonally-varying environment. As a non-ruminant herbivore it is well suited to a high fibre, low starch diet. Domestication
has resulted in a number of benefits to the horse, reflected in its continued prevalence and apparently increased life expectancy,
but it has not been without its price. Especially in developed countries, horses kept for leisure purposes (which includes
all competition and racing horses) are often confined, possibly away from conspecifics, within a stable for a large proportion
of the day. Due to increased energy requirements many horses now receive one to two large meals a day, consisting of feedstuffs
with a low water content and often a radically different nutritional profile from the diet that they would be able or would
choose to select in the wild. These modern practices have benefits but also potential disadvantages to the horse both nutritionally
and behaviourally which may have an impact on welfare. This chapter highlights areas where dietary imbalances or inappropriate
feeding practices may potentially have an adverse effect on welfare and gives suggestions on how these may be ameliorated.
The filterability of equine RBC and whole blood was evaluated to better understanding the effects of exercise-associated haemoconcentration and increased cardiac output on the flow properties of blood in the microvasculature. When RBC were filtered through filters with 3 m pores (3 m filters), the initial increase in filtration pressure (Pi) increased 4.6-fold between packed cell volumes (PCV) of 5% and 40%. Filters with 5 m pores had lower Pi at all PCV studied and the absolute increase in Pi with increasing PCV was minimal. Increasing the flow rate resulted in marked increases in Pi for 3 m filters. The Pi for 5 m filters also increased with increasing flow rate but values were consistently less than for 3 m filters. The Pi values for horse RBC were less than those for human RBC at all flow rates evaluated. Calculated wall shear stress values were much higher for 3 m filters than those for 5 m filters. Filtration pressures and wall shear stress values for whole blood were greater than those for RBC for both 3 m and 5 m filters. These data suggest that changes in PCV and flow rate may significantly alter shear forces in the microvasculature particularly in vessels approaching 3 m in diameter.
Many aspects of horse care and handling are based upon convenience and traditional practices. Many of these methods of management
and practice do not take into account the natural behaviour of horses. This is despite the belief that although domestic horses
are probably more docile, stronger, faster growing and faster moving than their ancestors, they are unlikely to have lost
any natural behaviours. The performance or sport horse is expected to perform a wide variety of movements and tasks, some
of which are unnatural or exaggerated and most of which must be learned. The term ‘training’ is commonly used to describe
the processes whereby the human handler introduces the horse to new situations and associations. Performance horses are often
required to tolerate stimuli that are innately aversive or threatening, such as having a person on their backs. They are also
trained to respond to a stimulus with often unnatural or over-emphasised behaviour, such as some of the dressage movements.
Effective and humane training requires an understanding of the processes underlying behaviour. These include knowledge of
behaviour under natural conditions, learning processes, the influence of early experience and motivational forces. Horses
differ from the other main companion animal species, namely cats and dogs, in that they are a prey species. They most commonly
flee from dangerous and painful situations. Horses readily learn to avoid potentially threatening situations and if their
attempts to avoid associated stimuli are prevented, they will often exhibit problem behaviours. In this chapter the history
of horse training, the application of learning theory and a knowledge of equine behaviour to training, and innovative training
methods are all considered.
Basement membranes are specialized extracellular matrices with support, sieving, and cell regulatory functions. The molecular architectures of these matrices are created through specific binding interactions between unique glycoprotein and proteoglycan protomers. Type IV collagen chains, using NH2-terminal, COOH-terminal, and lateral association, form a covalently stabilized polygonal framework. Laminin, a four-armed glycoprotein, self-assembles through terminal-domain interactions to form a second polymer network, Entactin/nidogen, a dumbbell-shaped sulfated glycoprotein, binds laminin near its center and interacts with type IV collagen, bridging the two. A large heparan sulfate proteoglycan, important for charge-dependent molecular sieving, is firmly anchored in the basement membrane and can bind itself through a core-protein interaction to form dimers and oligomers and bind laminin and type IV collagen through its glycosaminoglycan chains. Heterogeneity of structure and function occur in different tissues, in development, and in response to different physiological needs. The molecular architecture of these matrices may be regulated during or after primary assembly through variations in compositions, isoform substitutions, and the modifying influence of exogenous macromolecules such as heparin and heparan sulfate.
This article addresses many aspects of exercise-induced pulmonary hemorrhage (EIPH). Reports of the prevalence, effect on performance, and the clinical signs and means of diagnosis of EIPH are included. Radiologic and scintigraphic findings in horses with EIPH are reported. Pathogenesis and treatment are discussed.
New evidence confirmed that over 90% of Thoroughbreds have some degree of recurrent laryngeal neuropathy (RLN). This and the recognition that anything less than full extension of the atlanto-occipital joint in a racehorse implied a reduction in patency of the nasopharynx provided the basis of the hypothesis that exercise-induced pulmonary hemorrhage (EIPH) may be caused by an upper airway obstruction and that partial asphyxia could be the primary mechanism. EIPH was associated most frequently with the congenital (hereditary), left-sided, hemiparetic form of RLN. Other obstructive diseases, such as laryngeal chondritis and subepiglottic cysts, may be rare causes. Atlanto-occipital flexion on its own might also cause EIPH but more commonly was thought to be a factor which added to the upper airway obstruction resulting from RLN. Supporting evidence for this hypothesis was derived from retrospective and prospective studies of medical records; from necropsy findings on naturally occurring and experimentally produced cases of EIPH; from surveys on the prevalence of RLN; and from a literature review on asphyxia in man and animals.
The elastic constants and ultrastructure of the basement membrane of the crystalline lens of the adult cat have been investigated. Negatively stained specimens examined by electron microscopy revealed fragments of parallel filaments showing little tendency to cross over or link with each other. High resolution micrographs also showed that the filament spacing was about 4.3 nm while the filaments had a regular periodicity of 4.1 nm along their length. Optical defraction analysis of the filaments suggested a possible helical array, the angle of tilt of the helices being about 50 degrees. The elastic properties of the basement membrane were compared with those of a lightly vulcanized rubber membrane of the same thickness. At low stress values the Young modulus of elasticity of the basement membrane (0.82 × 106 N m-2) and rubber membrane (1.32 × 106 N m-2) were similar, but at moderate extension the basement membrane had a Young modulus of elasticity almost ten times greater than rubber which in contrast showed a slight decrease in elasticity. Also basement membrane had a low percentage of elongation (25%) compared with rubber (750%) but the ultimate stress required to rupture basement membrane was similar to that of rubber. These data suggest that the extension of coiled superhelices of the filaments rather than the extension of non-extensile randomly linked filaments, would be an appropriate model of basement membrane. This satisfactorily predicts the stress-strain curve, and ultimate stress of the intact membrane, while on the molecular level it predicts the angle of tilt of the superhelix (53 degrees) and indicates that the elasticity modulus of the filaments of which the membrane is composed is similar to the elasticity modulus of collagen filaments. Furthermore the change of entropy (1.0 --> 1.6 J K-1 per mole of collagenous protein polypeptide residue) has been calculated from the external work necessary to rupture the membrane. In terms of the model this presumes that all the superhelices of which the membrane is composed have passed from a helical to a non-helical or extended state before rupture. A similar estimate for the growth entropy of polypeptide chains has previously been made from thermodynamic measurements on binary polypeptide solutions which induce either a random or helical configuration.
Pulmonary capillaries have extremely thin walls to allow rapid exchange of respiratory gases across them. Recently it has been shown that the wall stresses become very large when the capillary pressure is raised, and in anaesthetised rabbits, ultrastructural damage to the walls is seen at pressures of 40 mm Hg and above. The changes include breaks in the capillary endothelial layer, alveolar epithelial layer, and sometimes all layers of the wall. The strength of the thin part of the capillary wall can be attributed to the type IV collagen in the extracellular matrix. Stress failure of pulmonary capillaries results in a high-permeability form of oedema, or even frank haemorrhage, and is apparently the mechanism of neurogenic pulmonary oedema and high-altitude pulmonary oedema. It also explains the exercise-induced pulmonary haemorrhage that occurs in all racehorses. Several features of mitral stenosis are consistent with stress failure. Overinflation of the lung also leads to stress failure, a common cause of increased capillary permeability in the intensive care environment. Stress failure also occurs if the type IV collagen of the capillary wall is weakened by autoantibodies as in Goodpasture's syndrome. Neutrophil elastase degrades type IV collagen and this may be the starting point of the breakdown of alveolar walls that is characteristic of emphysema. Stress failure of pulmonary capillaries is a hitherto overlooked and potentially important factor in lung and heart disease.
We previously showed that when the pulmonary capillaries in anesthetized rabbits are exposed to a transmural pressure (Ptm) of approximately 40 mmHg, stress failure of the walls occurs with disruption of the capillary endothelium, alveolar epithelium, or sometimes all layers. The present study was designed to determine whether some of the ultrastructural changes are rapidly reversible when the capillary pressure is reduced. To test this, the Ptm was raised to 52.5 cmH2O for 1 min of blood perfusion and then reduced to 12.5 cmH2O for 3 min of saline-dextran perfusion, followed by intravascular fixation at the same pressure. In another group of animals, the pressure was elevated for 1 min of blood and 3 min of saline-dextran before being reduced. The results were compared with previous studies in which the capillary pressures were maintained elevated at 52.5 cmH2O during the entire procedure. Control studies were also done at sustained low pressures. The results showed that the number of endothelial and epithelial breaks per millimeter and the total fraction area of the breaks were reduced when the pressure was lowered. For example, the number of endothelial breaks per millimeter decreased from 7.1 +/- 2.1 to 2.4 +/- 0.7, and the number of epithelial breaks per millimeter fell from 11.4 +/- 3.7 to 3.4 +/- 0.7. There was evidence that the breaks that closed were those that were initially small and were associated with an intact basement membrane. The results suggest that cells can move along their underlying matrix by rapid disengagement and reattachment of cell adhesion molecules, causing breaks to open or close within minutes.(ABSTRACT TRUNCATED AT 250 WORDS)
We previously showed that when pulmonary capillaries in anesthetized rabbits are exposed to a transmural pressure (Ptm) of approximately 40 mmHg, stress failure of the walls occurs with disruption of the capillary endothelium, alveolar epithelium, or sometimes all layers. The present study was designed to test whether stress failure occurred more frequently at high than at low lung volumes for the same Ptm. Lungs of anesthetized rabbits were inflated to a transpulmonary pressure of 20 cmH2O, perfused with autologous blood at 32.5 or 2.5 cmH2O Ptm, and fixed by intravascular perfusion. Samples were examined by both transmission and scanning electron microscopy. The results were compared with those of a previous study in which the lung was inflated to a transpulmonary pressure of 5 cmH2O. There was a large increase in the frequency of stress failure of the capillary walls at the higher lung volume. For example, at 32.5 cmH2O Ptm, the number of endothelial breaks per millimeter cell lining was 7.1 +/- 2.2 at the high lung volume compared with 0.7 +/- 0.4 at the low lung volume. The corresponding values for epithelium were 8.5 +/- 1.6 and 0.9 +/- 0.6. Both differences were significant (P less than 0.05). At 52.5 cmH2O Ptm, the results for endothelium were 20.7 +/- 7.6 (high volume) and 7.1 +/- 2.1 (low volume), and the corresponding results for epithelium were 32.8 +/- 11.9 and 11.4 +/- 3.7. At 32.5 cmH2O Ptm, the thickness of the blood-gas barrier was greater at the higher lung volume, consistent with the development of more interstitial edema. Ballooning of the epithelium caused by accumulation of edema fluid between the epithelial cell and its basement membrane was seen at 32.5 and 52.5 cmH2O Ptm. At high lung volume, the breaks tended to be narrower and fewer were oriented perpendicular to the axis of the pulmonary capillaries than at low lung volumes. Transmission and scanning electron microscopy measurements agreed well. Our findings provide a physiological mechanism for other studies showing increased capillary permeability at high states of lung inflation.
Results of recent investigations in humans and dogs indicate that gravity-independent factors may be important in determining the distribution of pulmonary blood flow. To further evaluate the role of gravity-independent factors, pulmonary blood flow distribution was examined using 15-microns radionuclide-labeled microspheres in five prone ponies over 5 h of pentobarbital sodium anesthesia. The ponies were killed, and the lungs were excised and dried by air inflation (pressure 45 cmH2O). The dry lungs were cut into transverse slices 1-2 cm thick along the dorsal-ventral axis, parallel to gravity. Radioactivity of pieces cut from alternate slices was measured with a gamma well counter. The main finding was a preferential distribution of pulmonary blood flow to dorsal-caudal regions and higher flow in the center of each lung slice when compared with the slice periphery. Flow was lowest in cranial and ventral areas. Differences of +/- 2 SD were observed between core and peripheral blood flow. No medial-lateral differences were found. Pulmonary blood flow distribution did not change over 5 h of anesthesia, and the basic flow pattern was not different in the left vs. right lung. These results suggest that in the intact prone mechanically ventilated pony (inspired O2 fraction greater than or equal to 0.95) factors other than gravity are primary determinants of pulmonary blood flow.
Stress failure of capillary walls has previously been demonstrated in anesthetized rabbit lungs at high capillary transmural pressures, and the ultrastructural changes in the walls have been described with transmission electron microscopy. In the present study, the pattern of alveolar epithelial disruptions was studied using scanning electron microscopy (SEM). Lungs of anesthetized rabbits were perfused with autologous blood at capillary transmural pressures of 12.5, 32.5, 52.5, and 72.5 +/- 2.5 cm H2O and fixed by intravascular perfusion. Samples for SEM were processed by critical point-drying and freeze-drying, and the results of the two techniques agreed well. Out of a total of 433 alveolar epithelial breaks examined, 93% were elongated, with the remainder being roughly circular; 68% of the elongated breaks were oriented perpendicular to the capillary axis, suggesting that the surface tension of the alveolar lining layer played an important role in protecting the blood-gas barrier against stress failure. Most of the breaks involved the full blood-gas barrier, but 17% were limited to the epithelial cells. This finding is consistent with our earlier conclusion that the extracellular matrix, particularly the type IV collagen, is responsible for much of the strength of the blood-gas barrier. The dimensions of the elongated breaks of the epithelium were approximately 4 microns (length) and 1 micron (width). They varied little with pressure, suggesting that once the disruption had occurred the stresses were greatly relieved. Breaks affecting the complete blood-gas barrier tended to be larger than those confined to the epithelium, again consistent with the protective role of the extracellular matrix. Almost no breaks occurred at intercellular junctions although many were seen within 1 micron of the junctions. This finding suggests that the junctions themselves have considerable mechanical strength, but that their rigidity may make the cell in the vicinity of the junction more vulnerable to mechanical failure.
The mammalian pulmonary blood-gas barrier is well known to be extremely thin. For example, in the human lung, half of the area of the barrier (the 'bulging' part) has a thickness of only 0.2-0.4 micron. We show here that the barrier is also immensely strong. This is an essential requirement because the capillary wall stresses during heavy exercise become very large (about 7 x 10(4) N/m2 = 70 kPa) when capillary pressure increases to 30 mmHg. Stress failure of the pulmonary capillary wall consistently occurs in experimental rabbit preparations at abnormally high pressures exceeding 40 mmHg and may be the cause of bleeding into the lung in galloping racehorses. The great strength of the thin side of the blood-gas barrier can be attributed to the extracellular matrix, especially the type IV collagen which is predominantly located in the very thin lamina densa. The alveolar wall is therefore particularly vulnerable to injurious agents which attack type IV collagen such as autoantibodies in Goodpasture's Syndrome and perhaps neutrophil elastase in emphysema. The combination of extreme thinness and great strength of the blood-gas barrier poses a unique design requirement.
Electronmicroscopic appearances of pulmonary capillaries were studied in rabbit lungs perfused in situ when the capillary transmural pressure (Ptm) was systematically raised from 12.5 to 72.5 +/- 2.5 cmH2O. The animals were anesthetized and exsanguinated, and after the chest was opened, the pulmonary artery and left atrium were cannulated and attached to reservoirs. The lungs were perfused with autologous blood for 1 min, and this was followed by saline-dextran and then buffered glutaraldehyde to fix the lungs for electron microscopy. Normal appearances were seen at 12.5 cmH2O Ptm. At 52.5 and 72.5 cmH2O Ptm, striking discontinuities of the capillary endothelium and alveolar epithelium were seen. A few disruptions were seen at 32.5 cmH2O Ptm (mostly in one animal), but the number of breaks per millimeter cell lining increased markedly up to 72.5 cmH20 Ptm, where the mean frequency was 27.8 +/- 8.6 and 13.6 +/- 1.4 (SE) breaks/mm for endothelium and epithelium, respectively. In some instances, all layers of the blood-gas barrier were disrupted and erythrocytes could be seen moving into the alveolar spaces. In about half the endothelial and epithelial breaks, the basement membranes remained intact. The average break lengths for both endothelium and epithelium did not change significantly with pressure. The width of the blood-gas barrier increased at 52.5 and 72.5 cmH2O Ptm as a result of widening of the interstitium caused by edema. The cause of the disruptions is believed to be stress failure of the capillary wall. The results show that high capillary hydrostatic pressures cause major changes in the ultrastructure of the walls of the capillaries, leading to a high-permeability form of edema.
In the mammalian lung, alveolar gas and blood are separated by an extremely thin membrane, despite the fact that mechanical failure could be catastrophic for gas exchange. We raised the pulmonary capillary pressure in anesthetized rabbits until stress failure occurred. At capillary transmural pressures greater than or equal to 40 mmHg, disruption of the capillary endothelium and alveolar epithelium was seen in some locations. The three principal forces acting on the capillary wall were analyzed. 1) Circumferential wall tension caused by the transmural pressure. This is approximately 25 dyn/cm (25 mN/m) at failure where the radius of curvature of the capillary is 5 microns. This tension is small, being comparable with the tension in the alveolar wall associated with lung elastic recoil. 2) Surface tension of the alveolar lining layer. This contributes support to the capillaries that bulge into the alveolar spaces at these high pressures. When protein leakage into the alveolar spaces occurs because of stress failure, the increase in surface tension caused by surfactant inhibition could be a powerful force preventing further failure. 3) Tension of the tissue elements in the alveolar wall associated with lung inflation. This may be negligible at normal lung volumes but considerable at high volumes. Whereas circumferential wall tension is low, capillary wall stress at failure is very high at approximately 8 x 10(5) dyn/cm2 (8 x 10(4) N/m2) where the thickness is only 0.3 microns. This is approximately the same as the wall stress of the normal aorta, which is predominantly composed of collagen and elastin. The strength of the thin part of the capillary wall is probably attributable to the collagen IV of the basement membranes. The safety factor is apparently small when the capillary pressure is raised during heavy exercise. Stress failure causes increased permeability with protein leakage, or frank hemorrhage, and probably has a role in several types of lung disease.
Arterial hypoxemia has been reported in horses during heavy exercise, but its mechanism has not been determined. With the use of the multiple inert gas elimination technique, we studied five horses, each on two separate occasions, to determine the physiological basis of the hypoxemia that developed during horizontal treadmill exercise at speeds of 4, 10, 12, and 13-14 m/s. Mean, blood temperature-corrected, arterial PO2 fell from 89.4 Torr at rest to 80.7 and 72.1 Torr at 12 and 13-14 m/s, respectively, whereas corresponding PaCO2 values were 40.3, 40.3, and 39.2 Torr. Alveolar-arterial PO2 differences (AaDO2) thus increased from 11.4 Torr at rest to 24.9 and 30.7 Torr at 12 and 13-14 m/s. In 8 of the 10 studies there was no change in ventilation-perfusion (VA/Q) relationships with exercise (despite bronchoscopic evidence of airway bleeding in 3) and total shunt was always less than 1% of the cardiac output. Below 10 m/s, the AaDO2 was due only to VA/Q mismatch, but at higher speeds, diffusion limitation of O2 uptake was increasingly evident, accounting for 76% of the AaDO2 at 13-14 m/s. Most of the exercise-induced hypoxemia is thus the result of diffusion limitation with a smaller contribution from VA/Q inequality and essentially none from shunting.
The efficacy of water vapor-saturated air as a treatment for horses with exercise-induced pulmonary hemorrhage (EIPH) was studied. Horses selected for study (n = 14) had grade 1 or greater hemorrhage in the trachea after a minimum of 4 breezes between 0.8 and 1 km, as determined by endoscopy. Nine horses were treated with water vapor-saturated air; 5 horses were not treated. When the mean and maximal EIPH scores from the pretreatment period were compared with the mean and maximal EIPH scores from the treatment period in both treated and nontreated groups, there was no significant difference between groups. There was a suggestion of a linear relationship between exercise speed and the mean EIPH score of the first 4 breezes in all 14 horses.
Dog left upper lobes (LUL) were perfused in situ via the left lower lobe artery. Lobe weight was continuously monitored. Increasing lobar flow from normal to 10 times normal had little effect on left atrial pressure, which ranged from 1 to 5 mmHg. There was a flow threshold (Qth) below which lobar weight was stable. Qth ranged from 1.1 to 1.55 l/min (mean 1.27) corresponding to four times normal LUL blood flow. Above Qth, step increases in lobar flow resulted in progressive weight gain at a constant rate that was proportional to flow. The effective pressure at the filtration site (EFP) at different flow rates was estimated from the static vascular pressure that resulted in the same rate of weight gain. From this value and from mean pulmonary arterial (PA) and left atrial (LA) pressures, we calculated resistance upstream (Rus) and downstream (Rds) from filtration site. At Qth, Rds accounted for 60% of total resistance. This fraction increased progressively with flow, reaching 83% at Q of 10 times normal. We conclude that during high pulmonary blood flow EFP is closer to PA pressure than it is to LA pressure, and that this becomes progressively more so as a function of flow. As a result, the lung accumulates water at flow rates in excess of four times normal despite a normal left atrial pressure.
This paper reviews a series of clinical, post mortem and imaging studies on exercise-induced pulmonary haemorrhage (EIPH) performed on 26 Thoroughbred racehorses. Post mortem techniques included routine gross, subgross and histological examination; coloured latex perfusions of pulmonary and bronchial circulations; and microradiography and computerised tomography scans of lungs with contrast injected vasculature. The major lesions were multiple, separate and coalescing foci of moderately proliferative small airway disease accompanied by intense neovascularisation of the bronchial circulation. As a result of bronchial artery angiogenesis, the systemic circulation dominated the vascular supply of the air exchange structures in affected areas, producing an apparent left to right shunt. Extensive areas of sequestered haemosiderophages indicated previous haemorrhage from vessels apparently supplied by the bronchial arteries. Diffuse and focal parenchymal destruction and connective tissue reactions in affected areas were considered to be secondary to localised haemorrhage and macrophage-induced damage. The aetiology of EIPH was not determined, but the multifocal, small airway-centred lesions indicated that low grade bronchiolitis, possibly of viral origin, was a factor. Gravitational effects also appear to contribute to dorsal distribution of the lesions. The mild focal and subclinical lesions confined to secondary lobules are thought to evolve into the serious lung pathology observed in EIPH cases through the effects of localised hypoxia induced by maximal exercise and partial airway obstruction. Once initiated, a vicious cycle of increasing inflammatory damage and further local bleeding is set in motion.
Lungs from 19 Thoroughbred racehorses with a history of exercise-induced pulmonary haemorrhage (EIPH) were studied using several forms of microscopy. Light microscopy of paraffin sections revealed three lesions in the caudodorsal region of the lungs from each horse. These correspond with the location of blue to brown stains seen at necropsy. These lesions include sequelae of bronchiolitis, hemosiderophages and increased connective tissue. Much of each of the lungs appeared normal, especially the more cranial or ventral portions. Foci of eosinophil infiltration were found in seven of the 19 lungs examined. With two exceptions, these eosinophilic foci had a different distribution to the three lesions. In areas of severe bronchiolar changes and fibrosis, vascular lesions typical of hypertension were found occasionally. Transmission electron microscopy was used to confirm cell types seen by light microscopy and to examine arterioles for changes characteristic of neovascularisation. Areas of enlarged airspaces from the vascular injected right lungs were examined by scanning electron microscopy. The balance of fibrosis and destruction varied in these areas, but none were as extensive as those seen in chronic obstructive pulmonary disease. The authors hypothesise that bronchiolitis and related neovascularisation are essential components of the aetiology of EIPH.
Gross post mortem examinations were performed on the lungs of 26 Thoroughbred horses of known exercise-induced pulmonary haemorrhage (EIPH) status. The most consistent finding was a variable degree of bilaterally symmetrical, dark discolouration of the dorsocaudal regions of the caudal lung lobes. In more severely affected lungs, the stained areas extended cranially along the dorsal surfaces of the lungs, and in some cases affected approximately one third of the lung surface. Discoloured areas of lung were denser than normal, collapsed less readily, often contained trapped air and were slow to inflate. The subpleural bronchial arteries were more prominent in the discoloured regions. Pleural adhesions were noted in two horses but were not related to the discoloured lung regions. It was concluded that the discoloured lesions have a complex pathogenesis and were related directly to previous bouts of EIPH. Associated with them were signs indicating probable partial small airway obstruction, decreased tissue compliance and direct involvement of the bronchial arterial circulation.
The distribution of pulmonary blood flow is influenced by gravity, regional lung expansion, and hypoxic pulmonary vasoconstriction. However, these factors cannot completely explain the three-dimensional distribution of blood flow in the lung. The present study was designed to see whether anatomically related factors could contribute. Regional blood pressure vs. flow curves were determined in 100-230 small parenchymal samples (0.3-0.4 ml) from 12 isolated perfused dog lungs held at constant inflation pressure. In each region four blood flows were measured using radioactively labeled microspheres, and the four corresponding regional perfusion pressures were determined by correcting the measured perfusion pressure for hydrostatic effects. There were considerable differences in the slopes of the pressure vs. flow curves among lung regions. Dorso-caudal regions of the lung had higher vascular conductances than ventrocephalad regions, independent of the vertical orientation of the lung or the inflation volume during injections of microspheres. Thus the distributions of regional vascular conductances were related to the anatomic location and were not related to gravity, nor were they caused by nonuniformities in regional lung expansion or by hypoxic vasoconstriction or edema.
The distribution of blood flow to the lungs was measured with labelled microspheres injected into horses before and during anaesthesia. Anaesthesia was induced with glycerol guaiacolate ether and ketamine, and maintained with the spontaneous breathing of halothane in oxygen. In a preliminary group of six horses, flow distribution was observed during anaesthesia in sternal, dorsal and right lateral recumbency. In two other groups, each of four horses, the flow distribution with time during either sternal or right lateral recumbency was observed. A small, constant proportion of the 15 micron diameter microspheres bypassed the lungs. No increase in shunting with anaesthesia was detected. Blood flow distributed predominantly cranioventrally in the conscious horse in concordance with the expected effects of hydrostatic forces within the lung. In the anaesthetized horse a stable distribution rapidly developed whereby the flow was directed preferentially caudodorsally and evenly divided between the left and right lungs regardless of whether the horse was on its back, side or sternum. We conclude that an unidentified factor overrides gravitational effects on perfusion in the anaesthetized horse. If under anaesthesia, ventilation were distributed according to gravity, hypoxia would arise from this disassociation of ventilation from perfusion. The hypoxia would be most intense in dorsal recumbency, and least intense in sternal recumbency. This was reflected in the degree of hypoxaemia observed. A small but significant change in flow distribution with the phase of the respiratory cycle was detected in the conscious, standing horse.
Philippine polo and racing horses were examined for exercise-induced pulmonary hemorrhage after their competitive exercise. Exercise-induced pulmonary hemorrhage occurred in 11.1% of the polo horses and 64% of the racing horses. None of the horses had blood at the nostrils.
Pressures in the right side of the heart and esophagus (pleural) have not been determined in the exercising equine subjects. In the present study, 8 healthy ponies were examined to determine the changes in these variables caused by 2 degrees of exercise done on a treadmill (heart rate:183 +/- 5 beats/min [trot] and 220 +/- 6 beats/min [canter]). Measurements were also made during both degrees of exertion 10 minutes and 120 minutes after furosemide (1.0 mg/kg) administration. It was observed that both gaits resulted in significant increases in pulmonary artery, right ventricular, and right atrial pressures. The pulmonary artery systolic, mean, and diastolic pressures during strenuous exertion were 306%, 252%, and 242% of the respective resting values. At canter, when respiratory frequency (138 +/- 4 breaths/min) is synchronized with stride frequency, the delta esophageal pressure approached 30.4 +/- 2.86 cm of water. During exercise 10 minutes after furosemide administration, the increment in right atrial pressure was markedly attenuated. During strenuous exertion 120 minutes after furosemide administration, the right atrial and pulmonary arterial pressures increased, but to a significantly lower level than did the prefurosemide values. However, the mean pulmonary artery pressure was still 240% of the resting value. It is concluded that marked pulmonary hypertension is a consistent feature of moderate, as well as strenuous, exertion in the pony. Although furosemide administration attenuated the pulmonary hypertension somewhat, the significance remains unclear.
The repeatability of endoscopic observations of exercise-induced pulmonary hemorrhage (EIPH) and the efficacy of furosemide as a prophylactic treatment of horses with EIPH were studied in Thoroughbred race horses after consecutive breezes (at or near maximum speed, approx 16 m/s). Of 56 horses examined greater than or equal to 2 times, 21 (38%) had identical EIPH scores, whereas 26 (46%) and 9 (16%) had scores that differed by greater than or equal to 1 grade. In 56 nontreated horses, there was good agreement between 2 consecutive observations (K = 0.59, Z = 4.54, P less than 0.001). Similar comparisons after placebo (saline solution) treatment of 21 horses yielded fair to good agreement, whereas poorer agreement was seen after furosemide treatment of 23 horses. Comparison of average and maximum EIPH scores of 44 horses with a minimum of 4 observations (2 nontreated, 1 saline-treated, and 1 furosemide-treated) indicated that although furosemide did not stop EIPH, it did reduce the EIPH score in 28 (64%) horses.
Furosemide, 0.5 to 1.0 mg per kilogram intravenously, was given to 20 patients with left ventricular failure after acute myocardial infarction. Within five to 15 minutes, average left ventricular filling pressure fell from 20.4 to 14.8 mm Hg, accompanied by a 52% increase in mean calf venous capacitance. During the same period there was no physiologically important change in either urine output or heart rate, blood pressure and cardiac output. Peak increase in urine flow (from mean of 0.82 to 4.0 ml per minute) occurred at 30 minutes, and peak natriuretic effect at 60 minutes. Thus, the action of furosemide in the treatment of pulmonary congestion is immediate and is not related to its diuretic properties. Rather, the prompt fall in left ventricular filling pressure probably is primarily vascular in origin, since marked changes in venous capacitance accompany this phenomenon, which is only later supplemented by the increase in urine output and electrolyte excretion.
Lung biopsy specimens were obtained from 4 patients during thoracotomy for mitral stenosis to study the effect of chronic pulmonary venous hypertension on the alveolar capillary wall. Electron microscopy showed edematous swelling of the capillary endothelial cells and thickening of their basal laminae which sometimes enclosed fragments of extravasated erythrocytes. Interstitial edema fluid was confined to the thicker collagen containing portions of the alveolar septa, and did not have the thinnest portions of the blood air barrier which are devoid of collagen and situated over the convexities of the alveolar capillaries. A proliferation of dense connective tissue surrounded some of the alveolar capillaries and displaced them inward from their normal superficial position in the alveolar wall. There was a proliferation of granular pneumocytes leading to the appearance of cuboidal cell metaplasia of alveolar walls and clumps of large mononuclear cells in the alveolar spaces.
To study the physical properties of renal tubular basement membranes directly, the epithelial layer of single isolated perfused rabbit proximal convoluted, proximal straight, and cortical collecting tubules was removed with sodium desoxycholate. Tubular segments were perfused using micropipets. The distal end of each segment was occluded in order to simplify the measurement of transmembrane water flow. The relation between outer tubular diameter and applied transmural pressure was identical in intact tubules and their respective isolated tubular basement membranes indicating that the basement membrane determines tubular distensibility. Young's modulus for basement membranes from all tubular segments corresponded to that of tendon collagen. Membrane hydraulic conductivity was measured in two ways: (a) from the rate of transmural flow in response to an applied difference in hydrostatic pressure and, (b) from the rate of transmural flow in response to a difference in colloid osmotic pressure. The hydraulic conductivity of tubular basement membranes was 300-800 times greater than that of the intact epithelial layer. Basement membrane hydraulic conductance was similar to that of peritubular and glomerular capillaries in vivo. The hydrostatic conductance of tubular basement membranes exceeded the osmotic conductance by 3-10-fold owing largely to the fact that the membranes were moderately permeable to the osmotic solute (albumin). In view of these findings we suggest that oncotic and hydrostatic pressure may play an important role in the movement of tubular absorbate from the epithelial compartment into the renal interstitium.
Type IV collagen was solubilized from a tumor basement membrane either by acid extraction or by limited digestion with pepsin. The two forms were similar in composition and the size of the constituent chains but differed when examined by electron microscopy and in the fragment pattern produced by bacterial collagenase. The acid-soluble form showed after rotary shadowing strands mainly of a length of 320 nm which terminated in a globule, or two strands connected by a similar globule. The globule was identified as a non-collagenous domain (NC1) which under dissociating conditions could be separated into two peptides showing a monomer-dimer relationship. Higher aggregates of NC1 were visualized under non-dissociating conditions. Some of the acid-extracted molecules have retained the previously 7-S collagen domain. The pepsin-solubilized form lacked domain NC1 and consisted mainly of four triple-helical strands (length 356 nm) joined together at the 7-S domain (length 30 nm). Common to both forms of type IV collagen was a small collagenase-resistant domain NC2 which was composed of collagenous and non-collagenous elements and located between the 7-S domain and the major triple helix. These data indicate that the collagenous matrix of basement membranes consists of a regular network of type IV collagen molecules which is generated by two different interacting sites located at opposite ends of each molecule. The 7-S collagen domain connects four molecules while the NC1 domain connects two molecules. The maximal distance between identical cross-linking sites (7-S or NC1) was estimated to be about 800 nm comprising the length of two molecules.
A flexible endoscope was used to obtain 223 tracheal washes from 191 horses in three clinical categories. Total cell counts, cytological and bacteriological examinations are reported and the features of the main cell types encountered described. The presence and degree of inflammatory airway disease was determined by a semiquantitative assessment of the neutrophil response and was an important consideration in the interpretation of the bacteriological results. Potential pathogens were isolated from approximately 30 per cent of samples. Cytological changes suggestive of lungworm infestation, virus infection and chronic airway disease are described. Haemosiderophages, indicative of pulmonary haemorrhage, were found in all horses in full training.
The techniques used were rapid and simple and were found to improve the accuracy of diagnosis of pulmonary disease. Sequential samples were useful for monitoring the progress of clinical cases.
We punctured subpleural microvessels in 19 isolated blood-perfused dog lung lobes to determine the effect of 5-hydroxytryptamine (5-HT) on the pulmonary microvascular pressure profile. Maintaining lobe airway pressure at 6 cmH2O and lobe venous pressure at 10 cmH2O we infused saline alone (10 microliter/min) in 10 control lobes and 5-HT in saline solution (100--150 micrograms/min) in 9 lobes. We measured pressures in subpleural microvessels using micropipettes connected to a servo-null system. The 5-HT infusion doubled lobar vascular resistance. In all microvessels upstream from the 150-micrometer venules, pressure was higher than in the control lobes. In contrast to the control lobes, pressure dropped markedly from the lobar artery to the 50-micrometer arterioles and from the venous capillaries to the 50-micrometer venules. We conclude that 5-HT not only constricted arterioles, but also raised lung microvascular pressure by constricting postcapillary venules.
Pleural and esophageal pressures were compared in 6 standing sedated ponies. Pleural pressure was measured with blunt needles attached to transducers and inserted in the 10th intercostal space level with and 10 and 20 cm above the point of the shoulder. Two balloons (a condom and an esophageal balloon) attached to transducers measured esophageal pressure in the cranial, middle, and caudal portions of the thoracic part of the esophagus. Tidal volume was measured by integrating a flow signal derived from a pneumotachograph attached to an endotracheal tube inserted through a tracheostomy. Frequency responses of all measuring systems were matched. Frequency responses of all measuring systems were matched. The change in pleural pressure during respiration was greatest in the middle and ventral portions of the thorax, less in the dorsal portion of the thorax and in the middle and caudal portions of the thoracic part of the esophagus, and least in the cranial portion of the thoracic part of the esophagus. The type of esophageal balloon had no effect on the measured pressure change. Regional variations in esophageal or pleural pressure during breathing caused variations in the calculated dynamic compliance. Pleural pressure gradients of 0.33 cm of water/cm of descent and 0.484 cm of water/cm of descent were recorded in the dorsal and ventral halves of the thorax, respectively, and may result in regional variations in lung inflation similar to those observed in persons.
Bleeding into the lungs in thoroughbreds is extremely common; there is evidence that it occurs in essentially all horses in training. However, the mechanism is unknown. We tested the hypothesis that exercise-induced pulmonary hemorrhage (EIPH) is caused by stress failure of pulmonary capillaries. Three thoroughbreds with known EIPH were galloped on a treadmill, and after the horses were killed with intravenous barbiturate the lungs were removed, inflated, and fixed for electron microscopy. Ultrastructural studies showed evidence of stress failure of pulmonary capillaries, including disruptions of the capillary endothelial and alveolar epithelial layers, extensive collections of red blood cells in the alveolar wall interstitium, proteinaceous fluid and red blood cells in the alveolar spaces, interstitial edema, and fluid-filled protrusions of the endothelium into the capillary lumen. The appearances were consistent with the ultrastructural changes we have previously described in rabbit lungs at high capillary transmural pressures. Actual breaks in the endothelium and epithelium were rather difficult to find, and they were frequently associated with platelets and leukocytes that appeared to be plugging the breaks. The paucity of breaks was ascribed to their reversibility when the pressure was lowered and to the fact that 60-70 min elapsed between the gallop and the beginning of lung fixation. Capillary wall stress was calculated from pulmonary vascular pressures measured in a companion study (Jones et al. FASEB J. 6: A2020, 1992) and from measurements of the thickness of the blood-gas barrier and the radius of curvature of the capillaries. The value was as high as 8 x 10(5) dyn/cm2 (8 x 10(4) N/m2), which exceeds the breaking stress of most soft tissues. We conclude that stress failure of pulmonary capillaries is the mechanism of EIPH.
Using catheter mounted microtip manometers, right atrial, pulmonary artery, and pulmonary artery wedge pressures were studied in 8 horses while they were standing quietly (rest), and during galloping at treadmill speeds of 8, 10, and 13 m/s. At rest, mean (+/- SEM) heart rate, mean right atrial pressure, mean pulmonary artery pressure, and mean pulmonary artery wedge pressure were 37 (+/- 2) beats/min, 8 (+/- 2) mm of Hg, 31 (+/- 2) mm of Hg, and 18 (+/- 2) mm of Hg, respectively. Exercise at treadmill belt speed of 8 m/s resulted in significant (P < 0.05) increments in heart rate, right atrial pressure, pulmonary artery systolic, mean, diastolic and pulse pressures, and pulmonary artery wedge pressure. All these variables registered further significant (P < 0.05) increments as work intensity increased to 10 m/s, and then to 13 m/s. Pulmonary artery diastolic pressure was, however, not different among the 3 work intensities. During exercise at belt speed of 13 m/s, heart rate, mean right atrial pressure, mean pulmonary artery pressure, pulmonary artery pulse pressure, and mean pulmonary artery wedge pressure were 213 (+/- 5) beats/min, 44 (+/- 4) mm of Hg, 89 (+/- 5) mm of Hg, 69 (+/- 4) mm of Hg, and 56 (+/- 4) mm of Hg, respectively. Assuming mean intravascular pulmonary capillary pressure to be halfway between the mean pulmonary arterial and venous pressures, its value during exercise at 13 m/s may have approached 72.5 mm of Hg. Transmural pressure (intravascular minus alveolar pressure) across pulmonary capillaries may be even higher because of the large negative pleural pressure swings in galloping horses.(ABSTRACT TRUNCATED AT 250 WORDS)
This study investigated changes in packed cell volume (PCV), pulmonary artery and aortic pressures, and the interaction between oesophageal pressure and pulmonary artery and aortic pressures during strenuous exercise in the horse. It was hypothesised that oesophageal pressure changes summate with pulmonary artery and aortic pressures during exercise and contribute to exercise-induced pulmonary haemorrhage (EIPH). Acute treadmill exercise (10 m/sec, 3 degrees incline) produced increases in heart rate (HR) from 50 to 202 beats/min; mean pulmonary artery pressure (PAP) from 28 to 80 mmHg; mean aortic pressure (AP) from 108 to 157 mmHg; and PCV from 0.35 to 0.52 litres/litre. EIPH was observed in three of seven horses after treadmill exercise, but no differences in the above variables were observed between the two groups of horses. Electronic subtraction of the oesophageal pressure signal from PAP and AP signals indicated peak transmural pressures of approximately 150 mmHg pulmonary and 175 mmHg aortic pressure. The elevated PAP associated with exercise appeared related more to increased HR and less to PCV (blood viscosity) or AP (bronchial). Both pulmonary artery and aortic peak transmural vascular pressures were substantially influenced by oesophageal pressure changes; peak and mean pulmonary artery and aortic pressures were significantly higher than resting pressures, and may conceivably contribute to EIPH.
1688) Markham's master-piece revived: containing all knowledge belonging ro the srnirh. furrier or horsc-leach
- G Markham
Markham, G. (1688) Markham's master-piece revived: containing all knowledge belonging ro the srnirh. furrier or horsc-leach... John Richardson for Tho.
The heredity of blood-vessel breaking in the thoroughbred. Bloodsrock Breeders' Rev. 2.265-28 I. Sweeney Exercise-induced pulmonary hemorrhage
- J B Robertson
Robertson, J.B. (1913) The heredity of blood-vessel breaking in the thoroughbred. Bloodsrock Breeders' Rev. 2.265-28 I. Sweeney. C.R. (1991) Exercise-induced pulmonary hemorrhage. Vet. Clin. North Am. 7.93-104.
Cardiopulmonary mechanisms of exercise-induced pulmonary hemorrhage and action of fumsemide
- H H Erickson
- M K Hopper
- S C Olsen
- N Pelletier
- B S Lowe
- C P Cope
Erickson, H.H., Hopper, M.K., Olsen, S.C., Pelletier, N., Lowe, B.S. and Cope, C.P. (1992) Cardiopulmonary mechanisms of exercise-induced pulmonary hemorrhage and action of fumsemide. Proc. Am. Ass. equine Practnrs. 37,65 1-661.
The heredity of blood‐vessel breaking in the thoroughbred
- Robertson J.B.
Cardiopulmonary mechanisms of exercise‐induced pulmonary hemorrhage and action of furosemide
- Erickson H.H.
Efficacy of furosemide in the treatment of exercise‐induced pulmonary hemorrhage in thoroughbred racehorses
- Pascoe J.R.