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Distal limb cryotherapy for the prevention of laminitis
Abstract
Acute laminitis can be a devastating consequence of systemic diseases such as severe colitis, proximal enteritis and metritis. Prophylactic therapies based on enhancing digital perfusion during the developmental phase of laminitis have resulted in only limited efficacy. Recent insights into the pathophysiology of acute laminitis have lead to the evaluation of cryotherapy for prevention of the disease. Experimental evidence demonstrates that the equine digit is particularly resilient with respect to the potentially detrimental effects of prolonged, extreme cold. Continuous distal limb cryotherapy during the developmental phase was effective in markedly reducing the severity of laminitis in an experimental model, and limited preliminary data suggests a similar effect in clinical cases of colitis. The mechanisms by which cryotherapy may prevent laminitis are unclear. Potent vasoconstriction of the digital circulation could prevent the delivery of systemic "trigger factors" to the digit. A cold-induced potent hypometabolic state within the laminar tissue may protect the laminae from damage regardless of the pathophysiological insult. The authors advocate the continuous application of cryotherapy to the distal limbs of clinical cases that are at high risk of developing acute laminitis. There is currently no evidence to support the use of cryotherapy in horses with preexisting acute laminitis.
... Modern hekimlikte lokal sağaltım olarak uygulanan soğuk su 32 yangının iyileşmesinde yardımcıdır. 33,34 Uygulamanın rasyonel nitelik taşıdığı söylenebilir. ...
... At bir hafta boyunca çalıştırılmadan dinlendirilir.(KK: 14,26,(33)(34)(35)(36)(37)(38)(39)(40) e. Eparven "Karakuş" olarak adlandırılır. Hastalık, ağır yük taşıyan atlarda şekillenir. ...
... Çam katranı apsenin üzerine sarılır.(KK: 14,26,33,(53)(54)(55)(56)(57)(58)(59)(60)(61) g. Dermatitis MadidansBukağılık çukurluğu derisinin hastalığına "bıcılgan" adı verilir. ...
Türkiye’nin İç Anadolu Bölgesi’nde yer alan Orta ve Yukarı Kızılırmak Havzası değişik uygarlık kalıntılarının birbiriyle kucaklaştığı, Anadolu’nun en eski yerleşim alanlarından biridir. İlk çağlardan beri yerleşim alanı olan bu topraklar çağlar boyunca Hitit, Frig, Kimmer, Pers, İskender, Roma ve Bizans İmparatorluklarının hâkimiyetinde kalmış ve bu toplumların kültürel varlıklarından etkilenmiştir. Bunlara ek olarak XI. yüzyıldan itibaren Anadolu’ya yerleşen Türklerin beraberlerinde getirdikleri kültür birikimleriyle bugünkü halk bilgilerinin temeli oluşturulmuştur.
Bu çalışmada, Orta ve Yukarı Kızılırmak Havzası folkloru içerisinde yer alan cerrahi ve dâhili at hastalıkları ve tedavi yöntemlerine ait bilgilerin modern veteriner hekimliği uygulamaları, teknikleri ve yeni tedavi modelleri açısından komparatif bir yöntemle ele alınması; at hastalıklarında kullanılan bitkisel, hayvansal ve madensel kökenli ilaç hammaddelerinden yola çıkılarak modern bilimin tedavi arayışlarına veri sağlanması amaçlanmıştır.
Çalışmanın materyalini, Orta ve Yukarı Kızılırmak Havzası içerisinde kalan yörelerde yaşayan halk hekimliği uygulayıcıları, hayvancılıkla uğraşan kişiler ve veteriner hekimlerden oluşan 211 kaynak kişiden toplanan veriler oluşturmuştur. Veri toplama amacıyla folklorik veteriner hekimliği ve hayvancılıkla ilgili sorulardan oluşan “Bilgi Derleme Formu” kullanılmıştır.
Elde edilen veriler sözlü, yazılı veya görsel olarak kayıt altına alınmıştır.
Çalışma ile dini-sihri tedaviler içerisinde, atın mezarlık etrafında gezdirilmesi ve sancı çubuklarının kullanımı; rasyonel tedavi kapsamında soğuk ya da sıcak su (hidroterapi), masaj, lavman, dağlama (kotarizasyon), tımar ve inhalasyon tedavilerinin; ampirik
tedavi içerisinde ise toprağa-gübreye gömme, kastrasyon ve terletme (koşturma) gibi tedavi yöntemlerinin uygulandığı belirlenmiştir.
Sonuç olarak, Orta ve Yukarı Kızılırmak Havzasında at hastalıkları ve terapilerin folklorik veteriner hekimliği açısından zengin öğeler barındırdığı, bölgede at hastalıklarında uygulanan tedavi yöntemlerinin dinî-sihrî, ampirik ve rasyonel nitelikler taşıdığı söylenebilir
... Also, the AVAs are important in thermoregulation. For example, in subfreezing conditions, periodic opening of the AVAs within the digit allows blood flow to be controlled such that cell viability is preserved while heat loss across the hoof capsule is minimized [3,12]. ...
... Distal limb cryotherapy has been established as a practical and effective means of preventing laminitis, provided that it is applied before clinical signs of laminitis appear [12]. The target temperature of around 5° C within the foot is easily attained with ice baths or boots, however it must be instituted and maintained during the developmental phase of the disease. ...
Systems theory is a way of describing complex and dynamic relationships. I applied systems theory to the structure and function of the equine foot in an effort to better understand laminitis and, in so doing, reconcile the various theories of its etiopathogenesis and find more universally effective preventive and therapeutic strategies. The foot is described as an open system, and its inherent vulnerabilities are explored. Cascade failure is discussed as a potentially unifying theory of laminitis. The fundamental failure in laminitis is failure of the lamellar dermal-epidermal bond, but that endpoint can be reached via vascular, enzymatic, inflammatory, or mechanical mechanisms, or any combination thereof. Inflammation is discussed as a common denominator, making anti-inflammatory therapy of greater importance than just pain management. Multimodal anti-inflammatory therapy is discussed, including selective COX-2 inhibitors, heparin, nutraceuticals, and inhibitors of MMPs. Multimodal analgesic therapy also is important and may include NSAIDs, opiates, epidural analgesics, physical therapy, relief of weight bearing, diligent nursing care, deep digital flexor tenotomy, and case-appropriate trimming and shoeing. Preventing laminitis still comes down to risk management: knowing the risk factors applicable to an individual horse and adjusting the management accordingly. Examples include weight management and control of carbohydrate intake in overweight horses and ponies, the use of pergolide in patients with PPID, and distal limb cryotherapy in high-risk patients. It is anticipated that application of molecular biological techniques will further advance treatment and prevention of laminitis.
... However, Pollitt has argued strongly against the hypoperfusion theory, stating that laminitis does not occur if the foot is in a state of vasoconstriction during the developmental phase (Pollitt 2004). This theory is also difficult to reconcile with the efficacy of cryotherapy as a treatment for the condition (van Eps et al. 2004). Instead, Pollitt argued that laminitis development coincides with an increase in sublamellar blood flow (Pollitt and Davies 1998), and this is certainly consistent with observations of an increase in hoof wall surface temperature during the developmental phase of laminitis in horses infused with insulin (de Laat et al. 2012). ...
... Its use has been more widespread in inflammatory forms of laminitis, where prediction of laminitis onset is easier than for endocrinopathic laminitis, where disease onset can be latent and insidious. Cooling of the limb can achieve a reduction in the severity of the lesion in acute disease (van Eps et al. 2004), and research is continuing into the timelines, temperatures and types of cooling that can achieve the best outcomes (van Eps and Orsini 2016; Morgan et al. 2018), while minimising pathologies associated with prolonged cooling (Proctor-Brown et al. 2018). ...
Despite the prevalence of endocrinopathic laminitis, the pharmacologic options for preventing and treating the disease are severely limited. The present review aims to discuss the spectrum of potential therapeutic agents for the condition, ranging from early experimental compounds to agents nearing registration. There are different pharmacologic targets for, and approaches to, managing laminitis. Reducing hyperinsulinaemia is central to diminishing endocrinopathic laminitis risk, and a detailed understanding of the pathophysiology of insulin dysregulation is necessary to identify pathways that can be targeted to minimise post-prandial insulin secretion and action. This area of research is advancing rapidly, with several exciting prospects, such as sodium-dependent glucose co-transporter-2 inhibitors, on the horizon for the treatment of equine metabolic dysfunction. Drugs that directly target the lamellae and aim to reduce the damage inflicted on the lamellae as part of this condition, are not yet available. Although progress in this area of laminitis therapy is slower, improved understanding of the events that lead to lamellar failure has enabled the investigation of novel drugs that aim to prevent laminitis at the site of the lesion. Finally, a brief review is included of the directions being taken in the management of the chronic and acute pain that accompanies laminitis. Medications for relieving the pain associated with laminitis are currently the most-prescribed drugs for the disease, and range from simple, affordable and thoroughly tested options, such as phenylbutazone, to newer, less-understood applications such as paracetamol and gabapentin. In the future, endocrinopathic laminitis management plans will likely take a multi-faceted approach that still hinge on effective dietary management and exercise, but also include drugs that address foot pathology, pain and underlying endocrine disturbances.
... Continuous application of cryotherapy (maintaining hoof wall surface temperature at 5°C-7°C) to the distal aspect of limbs for 48 hours prevents lameness, improves epidermal laminar histologic scores, reduces expression of messenger RNA for matrix metalloproteinase 2 (MMP-2), and reduces lamellar inflammatory signaling in horses with carbohydrate overload-induced laminitis. [11][12][13][14][15][16][17] In the only clinical study of cryotherapy for laminitis prophylaxis, Kullman et al found that horses with colitis were ten times less likely to develop laminitis when the limbs were cooled continuously for 48 hours or more. 18 This treatment is generally well tolerated by horses; however, it requires intensive management, replacing ice every 1-2 hours to have a constant ice slurry capable of keeping the hoof wall surface temperature below 10°C, as recommended. ...
... 18 This treatment is generally well tolerated by horses; however, it requires intensive management, replacing ice every 1-2 hours to have a constant ice slurry capable of keeping the hoof wall surface temperature below 10°C, as recommended. 17 Methods that incorporate the hoof, pastern, fetlock, and a portion of the cannon bone while still allowing some freedom of movement are needed for optimal hoof cooling. The most effective cooling methods are either 63 cm tall vinyl boots containing ice and water or a circulating refrigerated bath. ...
Colin F Mitchell, Lee Ann Fugler, Susan C Eades Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA Abstract: Laminitis is an extremely painful condition resulting in damage to the soft tissues anchoring the third phalanx to the hoof, which can result in life-threatening debilitation. Specific therapy is not available. The most important principles of therapy include aggressive nutritional and medical management of primary disease processes, cryotherapy, anti-inflammatory therapy, pain management, and biomechanical support. This review focuses on the principles of evidenced-based therapies. Keywords: laminitis treatment, laminitis biomechanics, laminitis pain
... Laminitis in septic equids has many similarities to organ injury in human sepsis; many of the same inflammatory events are now known to occur in sepsis-related laminitis (SRL) in horses [4][5][6][7][8], and, not surprisingly, we have seen a similar failure of pharmaceutical agents to consistently and effectively combat this disease [5]. However, in contrast to the situation in human sepsis, equine research both in the laboratory and clinical environment has resulted in characterisation of one effective therapy for sepsis-related laminitis: continuous digital hypothermia (CDH; also known as 'cryotherapy') [9][10][11]. ...
Background
Interleukin‐6 (IL‐6) is consistently increased in the digital lamellae in different studies of sepsis‐related laminitis (SRL). IL‐6 signalling through the gp130 receptor activates similar signalling (i.e. mTORC1‐related signalling) previously reported to be activated in models of endocrinopathic laminitis.
Objectives
To assess the activation state of signalling proteins downstream of IL‐6/gp130 receptor complex activation in an experimental model of SRL.
Study design
Randomised experimental study.
Methods
Lamellar phospho‐(P) protein concentrations downstream of the IL‐6/gp130 receptors were assessed in the oligofructose (OF) model of SRL. Fifteen Standardbred horses were administered water (CON, n = 8) or oligofructose (OF, n = 7) via a nasogastric tube. At 12 h post‐OF/water administration, one randomly assigned forelimb was exposed to continuous digital hypothermia (CDH) by placement in ice water (ICE, maintained at <7°C); the other forelimb was maintained at ambient temperature (AMB). Lamellar tissue samples were collected after 24 h of CDH from both ICE and AMB forelimbs and immediately snap‐frozen. Lamellar proteins of interest were assessed by immunoblotting and immunofluorescence.
Results
Immunoblotting revealed increase (P<0.05) in the phosphorylation states of Akt (Ser 473), RPS6 (Ser235/236), RPS6 (Ser240/244), STAT3 (Ser727) and STAT3 (Tyr705) in lamellar tissue from OF‐treated animals (AMB OF vs. AMB CON limbs); CDH resulted in decreased (P<0.05) lamellar concentrations of phosphorylated Akt, p70S6K, RPS6 (235/236), RPS6 (240/244) and STAT3 (S727) in OF‐treated animals (AMB OF vs. ICE OF). Immunofluorescence showed that activated/phosphorylated forms of RPS6 and STAT3 were primarily localised to lamellar epithelial cells.
Main limitations
The nature, sequence and timing of sub‐cellular events in this experimental model may differ from those that accompany naturally occurring sepsis.
Conclusions
There were increased lamellar concentrations of activated signalling proteins downstream of the IL‐6/Gp130 receptor complex in OF‐treated horses; CDH inhibited this activation for the majority of the proteins assessed. These results demonstrate similar lamellar signalling (e.g. mTORC1‐related signalling) and, therefore, possible therapeutic targets occurring in sepsis‐related laminitis as previously reported in models of endocrinopathic laminitis.
... For example, cryotherapy is considered an important aspect in the treatment of acute laminitis in the horse ( Kullmann et al., 2014). However, while there are several different types of cold therapy ( Van Eps et al., 2004), there has been little research done to provide empirical evidence towards the efficacy of the practice of applying cold therapy with the use of ice boots on the distal limb of the horse. Currently, recommended cryotherapy treatment protocol in the horse is extrapolated from human medicine ( Pollitt and Van Eps, 2004). ...
The limb of the equine athlete is subjected to all types of various stressors during exercise. To ensure the health of the horse and to prevent the possibility of lameness, it has been a common practice to apply cold therapy to the distal limb of the horse pre- and post-exercise. Commercially available boots are widely available for the application of cold therapy. To test the effectiveness of the boot, 6 healthy performance level sport type horses were exercised at a walk, trot, and canter in a round-pen and then subjected to the application of the ice boot for 20 minutes on a treatment leg, and no ice boot on an untreated leg. Thermal images were taken of the 3rd metacarpal region pre-exercise, post-exercise, post-ice boot, and every 2 minutes after until the difference between the temperatures of the control leg and the treatment leg became zero. The images were analyzed using an analysis software (FLIR Tools) to determine the average temperature of the 3rd metacarpal region at each time point. The measured temperatures between treatments were found to be significantly different due to the application of the ice boot, providing evidence that the boot sufficiently cools the leg (P<.01). Thereafter, a 95% confidence interval was created to depict the average time it took for the cooled leg to return to average temperature post-ice boot, suggesting that it takes about 14.67 minutes for the difference between the temperatures of the cooled leg versus the non-cooled leg to become zero. This finding is significant to horse owners, trainers, and veterinarians that use this commonly available tool. These findings lend evidence to support the common practice of using cold therapy in treatment of disease in the horse.
... The key to preventing severe chronic architectural changes in clinical cases may lie in the temporal identification of the active phase of lamellar damage. The length and timing of the developmental and acute phases varies widely depending on the inciting disease process (van Eps et al. 2004); biomarkers of active lamellar damage, currently under investigation ( Riggs et al. 2007), should help define this critical period. If weightbearing forces and mechanical distraction could be eliminated while the lamellae are compromised, the results of this study suggest that rapid stabilisation of the lamellar interface occurs, potentially preserving the lamellar architecture. ...
The histopathology of laminitis during its transition from the acute to the chronic phase has not been previously documented. Studying hoof lamellar tissues 7 days after induction of laminitis may provide insight into the intractable nature of the chronic phase of the disease.
To induce laminitis and investigate hoof wall lamellar tissues 7 days after dosing.
Laminitis was induced using oligofructose in 6 normal Standardbred horses. The dorsal hoof lamellar tissues of these and 12 normal horses were processed and examined by light microscopy. Serial sections of a lamellar tip affected by laminitis were used to create a 3 dimensional reconstruction.
Transverse sections of dorsal hoof wall lamellae were significantly longer than normal. Many secondary epidermal lamellae were not connected to primary lamellae and existed as spherical or ovoid, discrete islands isolated in the lamellar dermis. The lamellar basement membrane was intact.
Lamellar tissue has the ability to reorganise rapidly following an episode of acute laminitis. Although histopathological evidence of ongoing acute laminitis was absent by 7 days, there was marked disruption of lamellar architecture.
The architecture and subsequent strength of the resultant lamellar interface could be greatly influenced for the better by strategies that minimise mechanical displacement during the acute phase of laminitis.
Laminitis is a severely debilitating and life-threatening condition that occurs as a consequence of different primary triggering factors. Continuous digital hypothermia (CDH) is recommended in horses at risk of, or diagnosed with, acute laminitis due to its several physiological and biochemical alterations that may be positive for the prevention and early treatment of the condition, representing a low risk of adverse effects. Modulation of the inflammatory response, profound vasoconstriction, and prevention of tissue damage are the most notable protective effects of cryotherapy on the lamellae. This practical review aims to summarize the published literature evaluating CDH efficacy in the prevention and early treatment of acute laminitis in horses, highlighting the most important clinical findings and discussing the best methods to provide cryotherapy. Nineteen publications evaluated different CDH methods, including the use of commercially available ice boots or fluid bags filled with iced water or crushed ice, as well as alternatives to immersion in ice, e.g., frozen gel packs and a perfused cuff prototype. Although some techniques were effective for cooling and maintaining the hooves below the optimal temperature of 10 °C, relevant limitations such as labor intensiveness, reliance on an ice source and price make its use impractical in some clinical situations. Twelve experimental studies assessed the efficacy of CDH on the prevention or early treatment of laminitis, finding multiple positive effects in terms of clinical improvement, immunological and inflammatory modulation, and histological protection. After the analysis of the literature, the clinical importance of CDH in different stages of laminitis remains clear. However, it also highlights the need for a safer, more user-friendly, and more effective method of cryotherapy that can be used both in a hospital and an ambulatory setting.
An 11‐year‐old Arabian mare was presented to the Veterinary Teaching Hospital, Koret School of Veterinary Medicine because of acute colic. During exploratory laparotomy, a segment of the jejunum was found to be necrotic, with a haematoma on its antimesenteric border. The segment was removed via hand‐sewn resection and anastomosis, and the mare recovered successfully. Histopathology revealed intramural haematoma located in the tunica muscularis. Three years later, the mare is healthy, and is back to its intended use as a brood mare.
This article serves as an introduction into integrative case management as it applies to the horse's mental health, pain management, and tissue healing. The integrative philosophy pertains to the combination of conventional Western medicine and complementary and alternative therapies to provide the best patient care possible using currently available evidence. The goal is to improve the health of the patient in a more holistic manner.
Limb cellulitis/lymphangitis is a well‐recognised syndrome in horses, but there are limited published reports concerning outcomes and complications. This report describes a horse with hindlimb cellulitis/lymphangitis that developed ischaemia of the distal limb resulting in necrosis of the suspensory ligament branches and avulsion of the hoof capsule. A 16‐year‐old Thoroughbred mare was referred for further investigation and treatment of a left hindlimb cellulitis/lymphangitis. The culture of a swab taken from superficial pustules on the leg yielded a moderate growth of coliform bacteria and a profuse growth of Staphylococcus aureus. Treatment included systemic antimicrobials (based on the results of culture and sensitivity), phenylbutazone, dexamethasone, morphine and paracetamol. Following some initial clinical improvement, hyperextension of the metatarsophalangeal joint was noted on Day 5 of hospitalisation. Complete avulsion of the ipsilateral hoof capsule occurred on Day 10, and the horse was immediately euthanised. A limited post‐mortem examination revealed necrosis of the suspensory ligament branches. Fibrin thrombi, interstitial haemorrhage and oedema were identified in the suspensory ligament branches and adjacent subcutaneous tissues, with thrombi in relatively large vessels. The dermal laminae were extensively necrotic, and the majority of the lamellar vasculature contained fibrin thrombi.
This experimental study evaluated the cooling effect of ice bag cryotherapy on the hoof surface temperature in horses. In 6 horses one forelimb was cooled for 90 minutes using an ice water bag system applied between the carpus and the hooves, while the contralateral hoof served as control. Surface temperature of the hooves was determined using thermography before, during cooling and for 90 minutes following the end of cooling. Coronary and mid wall temperature was evaluated during the time course and compared with the contralateral hoof temperature. At 60 and 90 min cooling had a significant, but very small cooling effect of 1.4 °C at the coronary band, while at mid wall no significant temperature change was found. The cooling effect of three tightly fitting ice water bags around fetlock and cannon bone was only small. As this method acted by cooling the distal limb with the supplying arterial blood rather than the hoof itself, the hoof surface temperature probably underestimated the laminar temperature in an unknown extent. Ice bags do have the advantage, that they can be used also in horses, which should be allowed to lie down, like horses suffering from severe laminitis. However, these cooling effects are far from cooling effects of ice water immersion in rubber boots and possibly not effective for therapeutic purposes in laminitic horses.
Reasons for performing studyDigital hypothermia may be effective for laminitis prophylaxis and therapy, but the efficacy of cooling methods used in clinical practice requires evaluation.Objectives
To use hoof wall surface temperature (HWST) to compare several cooling methods used in clinical practice.Study designExperimental crossover design with a minimum washout period of 72 h.Methods
Seven cooling methods (commercially available ice packs, wraps and boots) and one prototypical dry-sleeve device were applied to a single forelimb in 4 horses for 8 h, during which HWST of the cooled forelimb and the uncooled (control) forelimb was recorded hourly. Results were analysed descriptively.ResultsThe median (range) HWST from 2-8 h was lowest for the ice and water immersion methods that included the foot and extended proximally to at least include the pastern: 5.2°C (range: 4.8-7.8°C) for the fluid bag and 2.7°C (2.4-3.4°C) for the ice boot. An ice boot that included the distal limb but not the foot resulted in a median HWST of 25.7°C (20.6-27.2°C). Dry interface applications (ice packs) confined to the foot only resulted in a median HWST of 21.5°C (19.5-25.5°C) for the coronet sleeve and 19.8°C (17.6-23°C) for a commercial ice pack. For the dry interface applications that included the foot and distal limb, the median HWST was much higher for the ice pack device, 19.9°C (18.7-23.1°C), compared with the perfused cuff prototype of 5.4°C (4.2-7°C).Conclusions
Immersion of the foot and at least the pastern region in ice and water achieved sustained HWST <10°C as did a prototype perfused cuff device with a dry interface. Variation between cooling methods may have a profound effect on HWST and therefore efficacy in clinical cases where laminitis prophylaxis or therapy is the goal.
The aim of this study was to evaluate the influence of the administration of anti-inflammatory drugs (NSAIDs) ketoprofen, phenylbutazone and flunixin meglumine on the apoptotic index of the epithelial cells of lamellar tissue of horses with induced laminitis. 20 healthy horses were employed and underwent induction of laminitis by administration of starch, divided into four groups with induced laminitis (n = 5): saline, ketoprofen, phenylbutazone and flunixin meglumine. The lamellar tissue was collected by biopsy, fixed and stained with the TUNEL technique. All that were stained positive by this technique were added to the cell morphological identification of apoptosis. No significant difference was found in the apoptotic index between the groups treated with anti-inflammatory and controls (P> 0.05). It was concluded that the administration of NSAIDs after the prodromal phase of laminitis does not contribute to an intervention in the course of apoptosis in the lamellar tissue of horses with laminitis when compared to the untreated control group. Other studies with different evaluation periods are needed to clarify the effects of anti-inflammatory non-steroidal drugs in the pathophysiology of laminitis in horses, especially regarding the role of apoptosis.
O objetivo deste trabalho foi avaliar a influência da administração dos anti-inflamatórios não esteroidais (AINEs) cetoprofeno, fenilbutazona e flunixin meglumine sobre o índice apoptótico de células epiteliais do tecido lamelar de cavalos com laminite induzida por administração de amido. Foram empregados 20 equinos hígidos, divididos em quatro grupos experimentais (n=5): solução salina, cetoprofeno, fenilbutazona e flunixin meglumine. O tecido lamelar foi coletado por biópsia, fixado e corado pela técnica de TUNEL. À marcação positiva por essa técnica adicionou-se a avaliação morfológica celular para identificação da apoptose. Não houve diferença significativa no índice apoptótico entre os grupos tratados com anti-inflamatórios e o controle (P>0,05). Os anti-inflamatórios não interferiram sobre o índice apoptótico possivelmente porque foram administrados após a fase prodrômica da laminite e/ou porque não são eficazes em alterar a dinâmica da apoptose. Concluiu-se que a administração de anti-inflamatórios não esteroidais após a fase prodrômica da laminite não contribui para uma intervenção no curso da apoptose no tecido lamelar de cavalos com laminite quando comparados ao grupo controle não tratado. Outros estudos, com diferentes períodos de avaliação, são necessários para esclarecer os efeitos dos anti-inflamatórios não esteroidais na fisiopatologia da laminite em equinos, especialmente no que concerne à participação da apoptose.
LAMINITIS has been an affliction of domesticated equids since at least 350BC when Aristotle made the first known reference to ‘barley disease’. A survey of 113,000 horses in the UK in 1996 found the prevalence of laminitis to be 7·1 per cent. Although extensive research has partially unravelled the pathogenesis, evidence is conflicting and the significance of the different theories remains to be substantiated. Most of the research has involved the induction of laminitis by oral administration of excess carbohydrate or black walnut extract. How these models compare with the development of laminitis associated with pasture, gastrointestinal disease or mechanical overload of a limb is unknown. There is sufficient evidence to indicate that many of the proposed theories are important and a common pathogenesis linking the theories may eventually be determined. Insufficient trials have been performed to evaluate the efficacy of treatments for laminitis and most recommendations are based on anecdotal reports and clinical impressions. Literature can be cited both to support and oppose most of the treatments currently used for laminitis. This article reviews the options for the treatment of acute laminitis and provides some comment on the arguments for and against their use. The management of horses with chronic laminitis will be discussed in Part 2 in the next issue.
This thesis offers a contemporary review of the biomechanics involved in the disease of equine laminitis with respect to the methods of prevention and treatment. It begins with an introduction of the anatomy of the equine foot and how that anatomy serves a biomechanical purpose. An emphasis on the forces acting on a normal equine foot is presented with respect to different periods of the stance phase. The reaction of the internal structures of the foot to impact shocks and weightbearing is also outlined. Using the most current data, a generalized overview of laminitis follows and each of the four distinct phases are covered in detail. Known risk factors for laminitis and identified epidemiologic trends as well as economic impact are presented. Laminitis is examined from a biomechanical perspective and how normal biomechanical forces may affect prognosis. The scientific literature review specifically relates to the biomechanical effects of current methods of laminitis prevention and treatment. A scientific journal manuscript is presented and outlines a study evaluating the center of pressure and load distribution in a population of normal horses utilizing a common, but unsubstantiated, treatment for acute laminitis.
Systems theory is a way of describing complex and dynamic relationships. We applied systems theory to the structure and function of the equine foot in an effort to better understand laminitis and, in so doing, reconcile the various theories of its etiopathogenesis and find more universally effective preventive and therapeutic strategies. The foot is described as an open system, and its inherent vulnerabilities are explored. Cascade failure is discussed as a potentially unifying theory of laminitis. The fundamental failure in laminitis is failure of the lamellar dermal−epidermal bond, but that endpoint can be reached via vascular, enzymatic, inflammatory, or mechanical mechanisms, or any combination thereof. Inflammation is discussed as a common denominator, making anti-inflammatory therapy of greater importance than just pain management. Multimodal anti-inflammatory therapy is discussed, including selective COX-2 inhibitors, heparin, nutraceuticals, and inhibitors of matrix metalloproteinases (MMPs). Multimodal analgesic therapy also is important and may include nonsteroidal anti-inflammatory drugs (NSAIDs), opiates, epidural analgesics, physical therapy, relief of weight bearing, diligent nursing care, deep digital flexor tenotomy, and case-appropriate trimming and shoeing. Preventing laminitis still comes down to risk management: knowing the risk factors applicable to an individual horse and adjusting the management accordingly. Examples include weight management and control of carbohydrate intake in overweight horses and ponies, the use of pergolide in patients with pituitary pars intermedia dysfunction (PPID), and distal limb cryotherapy in high-risk patients. It is anticipated that application of molecular biologic techniques will further advance treatment and prevention of laminitis.
Cryotherapy using circulating 1°C water and applied to all four limbs markedly reduced the severity of clinical and histological laminitis after experimental induction with oligofructose. The authors recommend the use of distal-limb cryotherapy for the prevention of laminitis in horses clinically at risk. Authors' address: (van Eps). © 2006 AAEP.
Laminitis poses a threat to all horses, and is widely considered as being one of the most important diseases of horses and a global equine welfare problem. The effects of laminitis lead to debilitation, development of pronounced digital pain, and great suffering in the afflicted animal. The precise pathophysiological processes that result in laminitic pain are poorly defined, and hence the delivery of effective palliative care is clinically challenging. Knowledge and understanding of pain states in other animal species may further aid the elucidation of equine laminitic pain mechanisms, guide the search for treatable causes of this multifactorial problem, and thereby help achieve enhanced therapeutic and palliative care. However, parallels drawn from pain states in other animals must consider species differences in both anatomy and physiology, and the specific nature of the laminitic disease process.
This article discusses the physiology of the normal feet of horses, in order to understand the pathogenesis of laminitis. It also discusses the use of cryotherapy to treat horses with laminitis.
Background Cold weather injuries (CWI) are of great military concern due to their wide-ranging impact on military readiness. Previous short-term studies have identified CWI to be more prevalent in African-Americans, infantrymen, and lower-ranking soldiers. The purpose of this cross-sectional study was to determine the occurrence of CWI hospitalizations in the U.S. Army from 1980 to 1999, and to identify possible trends, high-risk groups and/or activities. Methods: The U.S. Army Research Institute of Environmental Medicine Total Army Injury and Health Outcomes Database was searched for hospitalizations with ICD-9-CM codes for frostbite, hypothermia, immersion foot, chilblains, and other. information concerning each soldier included: gender, age, ethnicity, rank, occupation, type of injury, home of record, duty station, principle diagnosis, trauma code, and cause of injury. Data was available on the demographic composition of the Army, by year, and was used as the denominator when calculating the frequency of occurrence. Results: During the study period there were 2143 hospitalizations due to CWI. African-American men and women were injured approximately 4 times and 2.2 times as often as their Caucasian counterparts, respectively. Trauma and cause of injury codes indicate that about 80% of all CWI hospitalizations result on-duty and during organized training. The yearly rate of CWI hospitalization has declined from 38.2/100,000 in 1985 to 0.2/100,000 in 1999. Conclusions: Our data are consistent with previous research concerning the increased rate of CWI among African-Americans though further investigation appears warranted. The occurrence of most CWI during on-duty training suggests preventability. The decline in the overall rate of CWI hospitalizations is multifactorial.
The generally accepted view that rates of oxygen consumption of tissues and poikilotherms increase regularly with rising temperature was subjected to careful examination using brain slices and skin of rats and nine different species of aquatic and terrestrial animals. It was found that, although there are statements in the literature to the contrary, the influence of temperature is a regular one and respiration increases with rising temperature so that when rates of oxygen consumption are plotted against temperature the resulting curve is regular without dips or peaks except the maximum expected at the optimum temperature.
This article discusses the physiology of the normal feet of horses, in order to understand the pathogenesis of laminitis. It also discusses the use of cryotherapy to treat horses with laminitis.
Explants of horses' hooves remained intact for up to 8 days when incubated in Dulbecco's modified Eagle medium (D-MEM) containing 25 mmol/l glucose but separated within 36 h when incubated in saline. The separation occurred between the basal epidermal cells and their basement membrane which is characteristic of the hoof separation that occurs in laminitis. Separation of hoof explants was prevented by addition of glucose to saline and was induced by adding 2-deoxyglucose or aminophenylmercuric acetate to D-MEM. Glucose consumption by the hoof explants was inhibited by 2-deoxyglucose and aminophenylmercuric acetate. The explants consumed relatively large amounts of glucose during the first 2 days of incubation and then little over the next 6 days. Despite the reduced glucose consumption, the hoof explants did not separate over 8 days of incubation. The results indicated that the integrity of the hoof explants was initially dependent on consumption of glucose and provide a possible explanation for the development of laminitis caused by conditions such as carbohydrate overload, acute inflammatory conditions, corticosteroid therapy and hyperlipidaemia. It would be expected that these conditions would induce a major hormonally-mediated metabolic shift away from glucose consumption by many peripheral tissues. It is suggested, therefore, that if the metabolic change occurred faster than the hoof tissue could adapt to an alternative energy substrate, then hoof separation and laminitis would occur.
Cold weather injuries (CWI) are of great military concern due to their wide-ranging impact on military readiness. Previous short-term studies have identified CWI to be more prevalent in African-Americans, infantrymen, and lower-ranking soldiers. The purpose of this cross-sectional study was to determine the occurrence of CWI hospitalizations in the U.S. Army from 1980 to 1999, and to identify possible trends, high-risk groups and/or activities.
The U.S. Army Research Institute of Environmental Medicine Total Army Injury and Health Outcomes Database was searched for hospitalizations with ICD-9-CM codes for frostbite, hypothermia, immersion foot, chilblains, and other. Information concerning each soldier included: gender, age, ethnicity, rank, occupation, type of injury, home of record, duty station, principle diagnosis, trauma code, and cause of injury. Data was available on the demographic composition of the Army, by year, and was used as the denominator when calculating the frequency of occurrence.
During the study period there were 2143 hospitalizations due to CWI. African-American men and women were injured approximately 4 times and 2.2 times as often as their Caucasian counterparts, respectively. Trauma and cause of injury codes indicate that about 80% of all CWI hospitalizations result on-duty and during organized training. The yearly rate of CWI hospitalization has declined from 38.2/100,000 in 1985 to 0.2/100,000 in 1999.
Our data are consistent with previous research concerning the increased rate of CWI among African-Americans though further investigation appears warranted. The occurrence of most CWI during on-duty training suggests preventability. The decline in the overall rate of CWI hospitalizations is multifactorial.
To determine rate and degree of cooling for the superficial digital flexor tendon (SDFT) during a standard cryotherapy application in horses and evaluate in vitro effects of cooling on survival of tendon cells.
6 limbs of 5 adult horses and cultured cells obtained from SDFT of 3 adult horses during necropsy.
In vivo data were acquired by use of a thermocouple temperature probe inserted into the SDFT of a forelimb of each standing sedated horse. After baseline temperatures were recorded, a commercial compression splint with circulating coolant was placed on each selected limb, which was then exposed to cold treatment for 60 minutes. Temperatures were recorded at 30-second intervals. Mean minimum core temperature was calculated and used to design a protocol for in vitro cold treatment of cells. Specimens were obtained from the SDFT of horses during necropsy; tendon cells were cultured in suspension and exposed to 1-hour of cold treatment that mimicked the in vivo procedure. Viability of cells after cold treatment was compared with viability of cells maintained at body temperature.
After 1 hour of cold treatment, SDFT core temperature was reduced by a mean of 21.8 degrees C, reaching a mean minimum temperature of 10 degrees C. Viability did not differ significantly between cold-treated and control cells.
Results indicated that topical application of cryotherapy significantly reduced core SDFT temperature in standing sedated horses. Temperatures achieved in vivo during cold treatment were not detrimental to the in vitro viability of tendon cells.
The generally accepted view that rates of oxygen consumption of tissues and poikilotherms increase regularly with rising temperature was subjected to careful examination using brain slices and skin of rats and nine different species of aquatic and terrestrial animals. It was found that, although there are statements in the literature to the contrary, the influence of temperature is a regular one and respiration increases with rising temperature so that when rates of oxygen consumption are plotted against temperature the resulting curve is regular without dips or peaks except the maximum expected at the optimum temperature.
The therapeutic application of cold to the limbs of the horse appears to be widely employed for the treatment of a variety of painful and inflammatory conditions, primarily of the hoof and lower limbs. No mailer what the method of application, there appears to be little information available as to the effects, efficacy length of therapy and best method of application in the house. So as to assist the practitioner in making reasonable recommendations for the application of cold therapy, this paper reviews the scientific literature on the physiologic effects of cold therapy and discusses relevant issues related to the efficacy of cold therapy and particularly methods of application to the horse.
To study expression of interleukin-1beta (IL-1beta) in the digital laminae of horses in the prodromal stage of experimentally induced laminitis.
8 healthy adult horses with no signs of laminitis.
Black walnut extract was administered via nasogastric tube to 4 horses, and water was administered to the remaining 4 (controls). Complete blood counts and physical examinations were performed every 30 minutes after administration of black walnut extract or water. General anesthesia was induced when total WBC count decreased by 30% in horses given the black walnut extract and 3 hours after water administration in control horses. The left forefoot was perfusion fixed with neutral-buffered 10% formalin, and paraffin-embedded sections of the digit were used for in situ hybridization with an equine-specific IL-1beta probe.
IL-1beta mRNA expression was observed in perivascular cells of the small laminar venules and capillaries in all 4 horses given black walnut extract and in interstitial cells remote from the microvasculature in 1 of the 4. Other cellular components of the laminar tissue and cellular components of the digital arterioles and veins did not exhibit IL-1beta mRNA expression. Expression of IL-1beta mRNA was not detected in laminae from control horses.
Results suggest that IL-1beta mRNA is expressed by perivascular cells in the laminar tissues of horses in the prodromal stage of experimentally induced laminitis. This provides evidence of an inflammatory process during the prodromal stage of laminitis, indicating that local digital proinflammatory cytokine expression may be an initiating factor in laminitis.
Background: Surface cooling is frequently used in a number of conditions, especially traumatic, ischemic, burn, and neurologic injury to reduce the tissue damage. However, the protective mechanisms of cold therapy on traumatized tissues remain unclear. Tumor necrosis factor-α (TNF-α) is a fundamental mediator in inflammatory reactions and trauma-induced tissue injury. In the present study, we examined the microvascular response to TNF-α challenge and the effects of local cooling on the TNF-α–induced changes in the striated muscle of hamsters. Methods: By the use of the dorsal skinfold chamber preparation and in vivo fluorescence microscopy in combination with computer-based image analysis, we determined TNF-α–induced leukocyte rolling and adhesion to microvascular endothelium, capillary perfusion, venular leakage,and cellular apoptosis with and without surface cooling. Results: We found that topical administration of 2000 units TNF-α caused a progressive impairment of microvascular perfusion and increased leukocyte recruitment and vascular macromolecular leakage. Local cooling to 10°C for 60 minutes markedly (P < .05) inhibited the TNF-α–induced capillary perfusion failure and leukocyte response and slightly attenuated the increase of microvascular permeability after 180 minutes of stimulation. Furthermore, it was observed that 24 hours of TNF-α stimulation increased the number of apoptotic cells (ie, nuclear condensation and fragmentation) by 10-fold. This TNF-α–mediated effect was almost abolished by treatment with local hypothermia. Conclusion: These data suggest that the protective effect of surface cooling of traumatized tissue is due to its attenuation of the microvascular inflammatory response associated with the inhibition of the process of apoptosis. (Surgery 1999:126:881-9.)
SummaryA descriptive and matched case-control study of laminitis was conducted in 7 private practices and at the Texas Veterinary Medical Centre (TVMC) between May 1992 and July 1993. Out of 108 horses with laminitis, 19 acute (49%) and 20 chronic (51%) cases were seen in private practice and 16 acute (23%) and 53 chronic (77%) cases at the TVMC. Gastrointestinal disease was the most common problem in 19/35 horses (54%), occurring just prior to the onset of acute laminitis in all hospitals. Among all horses in the study, most commonly used drugs were phenylbutazone (68%), acepromazine (34%), dimethyl sulphoxide (DMSO) (27%), antibiotics of various types (19%) and flunixin meglumine (19%). Acepromazine, DMSO and flunixin meglumine were used more commonly in acute cases of laminitis compared to chronic cases. In acutely affected horses, DMSO and flunixin meglumine were used significantly more often at the TVMC. In chronic cases, phenylbutazone and antibiotics were used more often in private practice. Shoeing and trimming were more commonly part of the treatment protocol for chronic cases. There were no significant associations between age, breed, sex or weight and the occurrence of acute laminitis. Horses with chronic laminitis were significantly older (P=0.04) and more females tended to be affected (P=0.08).
ACUTE LAMINITIS has long been attributed to factors or events that precede the onset of laminitis. Between 1759 and 1907 the overconsumption of grain, inflammation of the feet, suppression of perspiration (anhydrosis), excessive rest, excessive bleeding, road concussion, poor shoeing, unilateral weight bearing, sudden environmental temperature changes, prolonged standing (in the cold and aboard ships), diarrhea, and postpartum complications were all designated as causes. Today, commonly listed etiologic factors include ingestion of large amounts of grain, cold water, lush grass, or black walnut shavings, repeated concussion, endometritis or other severe infections, colic, exhaustion, stress, drug toxicities, and endocrine dysfunctions. At Texas A&M University (Table 1) the factors recorded as the cause presume a causal relationship between some preceding event and the acute laminitis. Logically, any event that precedes laminitis might be a cause, but etiologic validity depends on the definition of “cause” and the role that coincidence might have in the appearance of the disease.
The effect of gradual cooling on discharge from sensory receptors in the gastrocnemius muscle of the cat has been studied. Either the entire muscle as it lay in an oil pool or the vicinity only of individual sensory organs was cooled 10 to 15° C below normal body temperature as monitored by a thermocouple inserted into the muscle. Slowing, in general, occurred in the discharge of deefferented annulospiral, flower-spray and tendon organ afferents, identified by conduction rates of individual units and characteristic patterns of response. The firing from spindles decreased at all tensions above that needed to sustain a steady discharge, with greater absolute decreases at higher tensions. Relative to control rates, annulospiral endings were probably affected more than flower-spray ones. The discharge from spindles having intact efferent innervation was also slowed.Alterations in central excitability may result from changes in afferent discharge produced by cooling of calf muscles. In decerebrate cats paralyzed with gallamine, monosynaptic reflexes elicited by submaximal stimulation of the severed lateral gastrocnemius nerve were reduced when the medial gastrocnemius muscle of the otherwise denervated leg was cooled. Decerebrate rigidity in the triceps surae muscle also decreased with cooling.
THE psychological impact of chemotherapy-induced alopecia represents one of the more devastating side effects of cancer chemotherapy and, in some instances, leads patients to refuse potentially curative chemotherapy. The problem of alopecia is severe when patients are treated with the anthracycline antibiotic, doxorubicin (adriamycin), which is beneficial in many types of cancer (e.g., breast, lung, ovary, sarcomas, lymphomas, and leukemias).1 2 3 4 5 6 In 1973, Luce and his co-workers achieved good protection against doxorubicin-induced alopecia in 12 of 15 patients by means of regional direction of chilled air to the scalp.7 More recently, Edelstyn's group used cryogel packs held on the scalp with . . .
Temperature has pronounced and complex effects on cellular physiology. Rates of enzymatic processes display an exponential change with temperature, as expressed by the Q10 relationship. The basis of these effects may be temperature induced phase transitions in membrane lipids and protein associated water, effects on bulk water and effects on the relationship between water and inorganic solutes. Hypothermia may be lead to a collapse in ionic regulation, leading to an uncontrollable and lethal calcium influx. Subfreezing temperatures may cause injury due to cellular freezing with subsequent excessive osmotic swelling, lyotropic effects or excessive osmotic shrinking due to extracellular freezing. Cells may protect themselves by freeze avoidance accomplished by removal of ice nucleators, production of proteinaceous antifreeze agents and accumulation of polyols. Alternatively they may secure extracellular freezing by production of extracellular ice nucleating agents, and counteract lyotropic effects and osmotic shrinking by accumulation of polyols which reduce ice content in a colligative manner.
Cooling of the scalp has been found to prevent hair loss following cytostatic treatment, but in order to obtain the hair preserving effect the subcutaneous temperature has to be reduced below 22 degrees C. In order to establish the relationship between epicutaneous and subcutaneous temperatures during cooling and rewarming and to measure the effect of scalp cooling on subcutaneous scalp blood flow, subcutaneous blood flow and epi- and subcutaneous temperatures were measured in the frontal region at the hairline border before and during cooling with a cooling helmet, during spontaneous rewarming of the cooling helmet and after removal of the rewarmed helmet in 10 normal subjects. Subcutaneous blood flow was reduced to about 25% of the postcooling control level during cooling. The flow was constantly reduced until the subcutaneous temperature exceeded 30-32 degrees C. A linear relationship between epicutaneous and subcutaneous temperatures could be demonstrated with the regression equation: s = 0.9 c + 4.9 (r = 0.99). In eight of the 10 subjects the subcutaneous temperature could be reduced below 22 degrees C with the applied technique. It is concluded that the hair preserving effect of scalp cooling during cytostatic treatment is mainly due to the metabolic effect of cooling, and only to a minor extent due to the flow reducing effect.
Crude synovial collagenase, an enzyme that may affect joint cartilage in rheumatoid arthritis, can destroy whole articular cartilage. To study this phenomenon under more specific conditions, we purified collagenase synthesized by primary cultures of rheumatoid synovium and used it to degrade collagen fibrils purified from human articular cartilage. These highly cross-linked fibrils were resistant to solubilization in acetic acid-pepsin extracts and, in comparison with skin collagen fibrils reconstituted without intermolecular cross-links, were somewhat resistant to the collagenase as well. However, the rate of cartilage collagen lysis was affected by changes in reaction temperature. At temperatures found within rheumatoid knee joints (36°C) collagenolysis was four times greater than at temperatures found in normal knee joints (33°C). Part of the benefit from anti-inflammatory therapy in rheumatoid arthritis may be secondary to decreasing intra-articular temperatures, thereby decreasing the rate a...
Over a 1 year period, profound local hypothermia was used for myocardial protection during aortic cross clamping for 57 cases of aortic valve replacement, 58 cases of mitral valve replacement, and 31 cases of multiple valve replacement. Cross clamp times ranged from 21 to 138 minutes. The overall hospital mortality rate was 4.7%. During the same period, 137 patients received one to three aorto coronary bypass grafts. In 88 the aorta was clamped during performance of distal anastomoses, with myocardial protection provided by profound local hypothermia. Cross clamp times ranged from 16 to 96 minutes. It is concluded that profound local hypothermia effected by continous flushing of the pericardial sac with cold saline provides satisfactory myocardial protection during aortic cross clamping for periods up to 90 minutes during cardiac valve replacement and during performance of distal anastomoses of aorto coronary bypass grafts with the saphenous vein.
Basement membranes (BM) are ubiquitous extracellular matrices found at the boundary between cells and the connective tissue stroma. In the last decade, great advances have been made in our understanding of the composition of normal BM and their role in glomerular filtration and cell attachment. In pathology, BM play a major role in diseases, ranging from the metabolic to the neoplastic and from the inherited to the immunologic. The scope of this review precludes a critical survey of the abundant literature available on the normal BM. We have attempted, therefore, to provide an overview of that current knowledge of BM that is relevant to an understanding of the pathology of these structures with the major focus on those diseases characterized by pathologic alterations of the BM.
Medical records of 116 horses admitted to the Texas Veterinary Medical Center between Jan 1, 1984 and Dec 31, 1991 with duodenitis/proximal jejunitis ( dpj ) were reviewed. The prevalence of laminitis was 28.4% (33/116; 95% confidence interval: 20.2 to 36.6%). The prevalence of dpj and DPJ -associated laminitis did not appear to vary significantly by year during the study period. Anamnesis, physical examination, clinicopathologic data, and initial treatment recorded at the time of admission were reviewed to determine risk factors associated with development of laminitis associated with dpj . A trend of increasing prevalence of laminitis with increasing weight was observed. Using a multiple logistic regression model, horses weighing ≥ 550 kg were approximately twice as likely to develop laminitis than horses weighing < 550 kg ( P = 0.048). Horses with hemorrhagic reflux observed at the time of admission were nearly twice as likely to develop laminitis than horses without hemorrhagic reflux ( P = 0.022).
Treatments administered prior to admission or at our clinic did not significantly affect development of laminitis, except for administration of heparin to prevent laminitis. Of 33 horses that developed laminitis associated with dpj , 2 had laminitis at the time of admission. These 2 horses were excluded from analysis of the effects of heparin administered as prophylaxis for laminitis; neither horse was treated with heparin. The proportion of horses that developed laminitis among horses that received heparin (0.0%; 0/12) was significantly ( P = 0.018) less than that among horses that did not receive heparin (29.8%; 31/104). Because of the small number of horses that received heparin and the retrospective design of this study, the clinical importance of this association could not be determined.
A herd of pregnant horses exposed to hoary alyssum through ingested hay developed acute and severe gastrointestinal toxicity accompanied by intravascular hemolysis. Postmortem lesions were consistent with these signs. Three horses had late-term abortions.
Thirty-two dorsal, mid-hoof wall, lamellar sections from 8 Standardbred horses, humanely killed 48 h after the administration of an alimentary carbohydrate overload, were sectioned and examined by light microscopy. Sections were stained with the connective tissue and basement membrane stains periodic acid-Schiff (PAS), Azan and periodic acid silver methanamine (PASM) and with routine haematoxylin and eosin (H&E). Lesions of the epidermal lamellae, attributable to laminitis, were graded in order of increasing severity from Grade N (normal), Grade 1 (mild), Grade 2 (moderate) to Grade 3 (severe and extensive). The grading system was based principally on changes to lamellar basement membrane (BM) which were clearly visible when the connective tissue stains PAS and PASM were used. Earliest changes were rounding of the basal cell nuclei and elongation of secondary epidermal lamellae (SELs). Secondary epidermal lamellae tips were pointed instead of round and the basement membrane had separated from the lamellae. In early Grade 1 lesions, this was obvious at the tips of the SELs where the BM had lifted to form teat-shaped bubbles. The absence of BM at the tips of secondary dermal lamellae, along with varying amounts of connective tissue, was considered a progression in severity and classified as Grade 2. Eventually, even the primary epidermal and primary dermal lamellae separated from each other and the empty shells of isolated BM, in what was once the tip of the primary epidermal lamella, signified that a global separation of the epidermal and dermal lamellae had occurred (Grade 3 lesion). The histopathological grading system correlated well with the degree of lameness at the time of euthanasia, (r2 = 0.94) and apparently described the severity of laminitis accurately. Disintegration of the BM and failure of its attachment to the basal cells of the epidermis appears to be one of the earliest pathological events to occur in acute laminitis and could be the change that initiates the collapse of the lamellar architecture. Histopathological diagnoses of laminitis are strengthened when based on sections stained with at least PAS, in addition to routine H&E and should exhibit evidence of the BM pathology described here.
The use of cryotherapy, i.e. the application of cold for the treatment of injury or disease, is widespread in sports medicine today. It is an established method when treating acute soft tissue injuries, but there is a discrepancy between the scientific basis for cryotherapy and clinical studies. Various methods such as ice packs, ice towels, ice massage, gel packs, refrigerant gases and inflatable splints can be used. Cold is also used to reduce the recovery time as part of the rehabilitation programme both after acute injuries and in the treatment of chronic injuries. Cryotherapy has also been shown to reduce pain effectively in the post-operative period after reconstructive surgery of the joints. Both superficial and deep temperature changes depend on the method of application, initial temperature and application time. The physiological and biological effects are due to the reduction in temperature in the various tissues, together with the neuromuscular action and relaxation of the muscles produced by the application of cold. Cold increases the pain threshold, the viscosity and the plastic deformation of the tissues but decreases the motor performance. The application of cold has also been found to decrease the inflammatory reaction in an experimental situation. Cold appears to be effective and harmless and few complications or side-effects after the use of cold therapy are reported. Prolonged application at very low temperatures should, however, be avoided as this may cause serious side-effects, such as frost-bite and nerve injuries. Practical applications, indications and contraindications are discussed.
Cellular metabolism is dependent on the local temperature in tissues. Induced hypothermia has been shown to be protective in a number of conditions, especially traumatic, ischemic, burn, and neurological injury. However, the protective mechanisms of cold therapy remain controversial and the hemodynamic changes in the microcirculation of striated muscles in response to hypothermia have not been studied in detail previously.
In this study, we investigated the microvascular response of local cooling and rewarming in the striated muscle of hamsters by use of the dorsal skinfold preparation and in vivo fluorescence microscopy.
We found that reduction of the surface temperature to 8 degrees C for 30 minutes caused arteriolar vasoconstriction with a decrease in diameters by 43+/-7% while the venular and capillary diameters remained unchanged. The cooling procedure also markedly reduced the functional capillary density and the blood flow velocity and diameters in all vessel types, i.e., arterioles, venules, and capillaries. Moreover, the percentage of capillaries with no flow increased from 0.4+/-0.5% to 44+/-14% after 10 minutes of cold therapy. However, these hemodynamic changes induced by local hypothermia were completely reversed to the precooling values after termination of cooling and 30 min of rewarming. Strikingly, we found no increase in the number of adherent leukocytes and vascular permeability after the cooling and rewarming period, while, in contrast, additional experiments with warm ischemia (30 minutes) and reperfusion (30 minutes), i.e., reduced microvascular perfusion and reperfusion at normothermia, caused a sustained decrease in local perfusion and a nine-fold increase in venular leukocyte adhesion.
Taken together, our functional data demonstrate that hypothermia markedly reduces microvascular perfusion, which is completely restored upon rewarming. The reduced microvascular perfusion during hypothermia did not provoke an inflammatory response, whereas leukocyte recruitment was prominent after reduced perfusion at normothermia, indicating that transient hypothermia has no adverse effects on microvascular parameters in the striated muscle in vivo.
To characterize horses with acute diarrhea and determine risk factors for failure to survive.
Retrospective study.
122 adult horses admitted for acute diarrhea at the teaching hospital between Jan 1, 1990 and Dec 31, 1996.
Medical records of horses with acute diarrhea were reviewed to abstract information regarding signalment, history, physical examination, clinicopathologic testing, treatment, and outcome.
91 of 122 (74.6%) horses lived and were discharged from the hospital. Horses with history of administration of antimicrobials for a problem preceding diarrhea were approximately 4.5 times less likely to survive. The following variables that had been determined at the time of admission were significantly associated with failure to survive: administration of antimicrobial drugs for another illness, serum creatinine concentration > 2.0 mg/dl, PCV > 45%, tachycardia (heart rate > 60 beats/min), and low serum total protein concentration. Prevalence of laminitis was 11.5%.
Diarrheic horses that are azotemic and have clinicopathologic findings consistent with hemoconcentration and hypoproteinemia have a poor prognosis for survival. Antimicrobial administration may induce diarrhea, and antimicrobial-associated diarrhea may have a worse prognosis than other types of acute diarrhea.
The objective of this study was to elucidate how cryotherapy after anterior cruciate ligament reconstruction affects intraarticular temperature and clinical results. A prospective and randomized study was performed on 21 knees of 21 patients. The ligament reconstruction was performed by single-incision arthroscopy using autogenous hamstring tendon. On completion of the surgery, thermosensors were implanted in the suprapatellar pouch and the intracondylar notch, and the intraarticular temperature was monitored while the joint was cooled. Cooling was performed in one group at 5 degrees C (N = 7) and in another at 10 degrees C (N = 7), for 48 hours. A control group (N = 7) did not undergo cryotherapy. The cooled groups showed three temperature phases: a low-temperature phase immediately after the ligament reconstruction, followed by a temperature-rising phase and a thermostatic phase. The control group had no low-temperature phase and immediately entered a thermostatic phase. During the low-temperature phase in the treated groups, the temperature of the suprapatellar pouch and of the intercondylar notch were significantly lower than the body temperature. The pain score and the number of times an analgesic had to be administered were both significantly lower in the 10 degrees C group than in the control group. Blood loss was significantly less in the 5 degrees C group than in the control group.
Each horse with laminitis is presented to the veterinarian at a different stage in progression of the condition and with varying severity. The pathogenic timing is often unknown and is difficult to determine. Because timing and severity are related to both the lesion's severity and responsiveness to treatment, these factors are critical to treatment selection and success. It is erroneous to assume that each horse with laminitis should receive each treatment. It is therefore important to ascertain as logically and objectively as possible the pathophysiological stage of development of each horse when it is examined. Therapeutic failure may result from inappropriate interpretation of the clinical signs and pathophysiologic condition of the patient in order to coordinate a treatment regimen.
This review implies that although we know more regarding the enigma of developmental and acute laminitis today than previously, there is still more to investigate. As these investigations are conducted and interpreted, new and more effective preventive and therapeutic regimens are likely to be developed, tested, and made available. As this occurs, the impact of laminitis should undoubtedly decrease. Unfortunately, due to the lack of clinical symptoms in the developmental phase and the shortness of the acute phase, it is also evident that the two sequelae of acute laminitis, subacute and chronic laminitis, are likely to continue to pose a major problem for some time.
This article attempts to provide a historical perspective regarding equine laminitis. It is designed to cover, as completely as possible, the historical record of, and the research advances made, in regards to acute and chronic laminitis. With respect to the historical record, the names given to this disease, the postulated etiologies, and the various treatment protocols are discussed. This article demonstrates the historical longevity of this disease and establishes a background for the current understanding of the disease's pathologic mechanisms and treatments.
Surface cooling is frequently used in a number of conditions, especially traumatic, ischemic, burn, and neurologic injury to reduce the tissue damage. However, the protective mechanisms of cold therapy on traumatized tissues remain unclear. Tumor necrosis factor-alpha (TNF-alpha) is a fundamental mediator in inflammatory reactions and trauma-induced tissue injury. In the present study, we examined the microvascular response to TNF-alpha challenge and the effects of local cooling on the TNF-alpha-induced changes in the striated muscle of hamsters.
By the use of the dorsal skinfold chamber preparation and in vivo fluorescence microscopy in combination with computer-based image analysis, we determined TNF-alpha-induced leukocyte rolling and adhesion to microvascular endothelium, capillary perfusion, venular leakage, and cellular apoptosis with and without surface cooling.
We found that topical administration of 2000 units TNF-alpha caused a progressive impairment of microvascular perfusion and increased leukocyte recruitment and vascular macromolecular leakage. Local cooling to 10 degrees C for 60 minutes markedly (P < .05) inhibited the TNF-alpha-induced capillary perfusion failure and leukocyte response and slightly attenuated the increase of microvascular permeability after 180 minutes of stimulation. Furthermore, it was observed that 24 hours of TNF-alpha stimulation increased the number of apoptotic cells (i.e., nuclear condensation and fragmentation) by 10-fold. This TNF-alpha-mediated effect was almost abolished by treatment with local hypothermia.
These data suggest that the protective effect of surface cooling of traumatized tissue is due to its attenuation of the microvascular inflammatory response associated with the inhibition of the process of apoptosis.
Laminitis has been a recognized disease since early Greek and Roman times, but it is still bothering both practitioners and scientists. In the last decade a lot of new fundamental research has been done to elucidate the pathogenesis of laminitis. New insights into the pathogenesis, the predisposing factors (including nutritional overload, endotoxaemia, shock, management, etcetera), clinical and radiological signs, differential diagnosis, therapy, and prognosis of the disease are described. The data, however, are not always in agreement with each other, giving further proof of the complexity of the syndrome.
Alopecia is a distressing side-effect of cancer treatment. Taxanes (TX), anthracyclines (ANR) and etoposide (ET) have been consistently associated with significant alopecia. We studied an effective scalp cooling system, the Penguin Cold Cap system, for the prevention of chemotherapy-induced alopecia in 70 patients receiving chemotherapy, including one of the following major alopecia-causing agents: Group A, TX-based regimes (without ANR); Group B, TX+ANR; Group C, ANR-based regimes (without TX); Group D, ET-based regimes. Protection from hair loss was achieved by maintaining scalp temperatures below 15 degrees C before, during and after chemotherapy by frequent changing of the caps. Assessment was carried out using a grading system from 0 to 4. Grades 0-2 were considered as satisfactory hair protection, whilst Grades 3-4 were considered failures. 57 patients were evaluable for assessment. An overall 81% protection was achieved. In groups C and D 11 of 12 patients (92%) had no alopecia, whilst 30 of 34 patients (88%) treated with taxanes had adequate hair protection. In Group B, 4 of 11 patients (36%) had adequate hair protection. The system was well tolerated and is a very effective method for protection from hair loss caused by TX, ANR and ET. Our results are comparable with and, in most cases, better than those reported in other studies using various alopecia preventive methods.
Utilizing an in vitro laminitis explant model, we have investigated how bacterial broth cultures and purified bacterial proteases activate matrix metalloproteinases (MMPs) and alter structural integrity of cultured equine lamellar hoof explants. Four Gram-positive Streptococcus spp. and three Gram-negative bacteria all induced a dose-dependent activation of MMP-2 and MMP-9 and caused lamellar explants to separate. MMP activation was deemed to have occurred if a specific MMP inhibitor, batimastat, blocked MMP activity and prevented lamellar separation. Thermolysin and streptococcal pyrogenic exotoxin B (SpeB) both separated explants dose-dependently but only thermolysin was inhibitable by batimastat or induced MMP activation equivalent to that seen with bacterial broths. Additionally, thermolysin and broth MMP activation appeared to be cell dependent as MMP activation did not occur in isolation. These results suggest the rapid increase in streptococcal species in the caecum and colon observed in parallel with carbohydrate induced equine laminitis may directly cause laminitis via production of exotoxin(s) capable of activating resident MMPs within the lamellar structure. Once activated, these MMPs can degrade key components of the basement membrane (BM) hemidesmosome complex, ultimately separating the BM from the epidermal basal cells resulting in the characteristic laminitis histopathology of hoof lamellae. While many different causative agents have been evaluated in the past, the results of this study provide a unifying aetiological mechanism for the development of carbohydrate induced equine laminitis.
1. Prolonged exposure of the extremities to cold insufficient to cause tissue freezing produces a well-defined syndrome. 'Immersion foot' is one of the descriptive but inaccurate terms applied to this syndrome. The clinical features, aetiology, pathology, prevention, and treatment of immersion foot are considered in detail. A discussion on pathogenesis is also included. 2. In the natural history of a typical case of immersion foot there are four stages: the period of exposure and the pre-hyperaemic, hyperaemic, and post-hyperaemic stages. 3. During exposure and immediately after rescue the feet are cold, numb, swollen, and pulseless. Intense vasoconstriction sufficient to arrest blood-flow is believed to be the predominant factor during this phase. 4. This is followed by a period of intense hyperaemia, increased swelling, and severe pain. Hyperaemia is due to the release in chilled and ischaemic tissues of relatively stable vasodilator metabolites; pain may be the result of relative anoxia of sensory nerve-endings. 5. Within 7-10 days of rescue the intense hyperaemia and swelling subside and pain diminishes in intensity. A lesser degree of hyperaemia may persist for several weeks. Objective disturbances of sensation and sweating and muscular atrophy and paralysis now become apparent. These findings are correlated with damage to the peripheral nerves. 6. After several weeks the feet become cold-sensitive; when exposed to low temperature they cool abnormally and may remain cold for several hours. Hyperhidrosis frequently accompanies this cold-sensitivity. The factors responsible for these phenomena are incompletely understood; several possible explanations are considered. 7. Severe cases may develop blisters and gangrene. The latter is usually superficial and massive loss of tissue is rare. 8. The hands may be affected but seldom as severely as the feet. The essential features of immersion hand are the same as those of immersion foot. 9. Prognosis depends upon severity. The extent of anaesthesia at 7-10 days has been found a useful guide to the latter, and has formed a basis of a method of classification. 10. Rapid warming of chilled tissues is condemned. Cold therapy is of value for the relief of pain in the hyperaemic stage, but should not be used in the pre-hyperaemic stage. Sympathectomy and other measures designed to increase the peripheral circulation should not be employed immediately after rescue, but may have a place in the treatment of the later cold-sensitive state. This paper records the results of observations made during 1941 and 1942. Delay in publication has been necessary because of war-time difficulties of maintaining contact between authors. In this respect we have received much help from Surgeon Rear-Admiral J. W. McNee. We wish to thank Professors R. S. Aitken and J. R. Learmonth for much helpful advice during the preparation of the paper. The charts have been prepared by the technical staff of the Wilkie Surgical Research Laboratory, University of Edinburgh. During the period of the study, one of us (R. L. R.) was in receipt of a personal grant from the Medical Research Council.
The hypometabolic and vasoconstrictive effects of cryotherapy could prevent the development of laminitis.
To use distal limb cryotherapy to prevent laminitis induced by alimentary carbohydrate overload.
Laminitis was induced in 6 Standardbred horses that had one front limb continuously cooled in an ice/water mixture. Lameness evaluation, blinded lamellar histological grading and analysis for lamellar matrix metalloproteinase-2 (MMP-2) mRNA expression were used to evaluate the severity of laminitis.
Cryotherapy was well tolerated and effective in cooling the feet. In each horse no lameness was observed in the treated limbs. Laminitis histology scores in the treated limbs were significantly less than those of the corresponding untreated forelimbs (P < 0.05). Laminitis histology scores in the treated limbs were also significantly less than those of the untreated limbs (fore- and hind) as a group (P < 0.05). Expression of MMP-2 mRNA in the iced feet was significantly (P < 0.05) less than that detected in the untreated feet.
Cryotherapy, when applied to one foot, markedly reduced the severity of acute laminitis in this study. We propose that vasoconstriction (preventing delivery of haematogenous trigger factors) and hypometabolism (reduction in lamellar MMP activity) were the primary therapeutic mechanisms.
Although further research is needed, we suggest cryotherapy as a potentially effective prophylactic strategy in horses at risk of developing acute laminitis.
The dysadhesion and destruction of lamellar basement membrane of laminitis may be due to increased lamellar metalloproteinase activity. Characterising lamellar metalloproteinase-2 (MMP-2) and locating it in lamellar tissues may help determine if laminitis pathology is associated with increased MMP-2 transcription.
To clone and sequence the cDNA encoding lamellar MMP-2, develop antibody and in situ hybridisation probes to locate lamellar MMP-2 and quantitate MMP-2 transcription in normal and laminitis tissue.
Total RNA was isolated, fragmented by RT-PCR, cloned into vector and sequenced. Rabbit anti-equine MMP-2 and labelled MMP-2 riboprobe were developed to analyse and quantitate MMP-2 expression.
Western immunoblotting with anti-MMP-2 detected 72 kDa MMP-2 in hoof tissue homogenates and cross-reacted with human MMP-2. Immunohistochemistry and in situ hybridisation detected MMP-2 in the cytoplasm of basal and parabasal cells in close proximity to the lamellar basement membrane. Northern analysis and quantitative real-time PCR showed MMP-2 expression significantly (P < 0.01) elevated in laminitis affected tissues.
The lamellar pathology of laminitis is associated with increased transcription of MMP-2.
Real-time PCR analysis of lamellar MMP-2 accurately monitors laminitis development at the molecular level and can be used diagnostically and for testing preventive strategies. Controlling increased MMP-2 transcription may ameliorate or prevent laminitis in high risk clinical situations. Our findings represent a warning to clinicians that the basement membrane lesion of laminitis is insidious and well under way before clinical signs are apparent.
The recommended duration of cryotherapy in horses is currently extrapolated from human medicine. Prolonged, continuous cryotherapy (days rather than minutes) may be of therapeutic value if it is safe and well tolerated.
To evaluate the effect of prolonged, continuous application of ice and water to the equine distal limb.
A slurry of ice and water was applied to the right forelimb of 4 Standardbred horses for 48 h. Hoof temperature, ambient temperature and ice boot temperature were logged continuously and clinical observations recorded every 2 h. Lameness examinations were performed prior to application and 1 week, 6 months and 1 year after removal of the ice boot.
Continuous cryotherapy was well tolerated and resulted in marked cooling of the treated foot. No significant variation in clinical parameters was noted, and no lameness or gross pathology noted in the treated limbs at any examination period.
The continuous application of ice and water is a safe and effective means of cooling the equine distal limb. The extremely low, constant temperatures achieved may be of benefit in the management of various distal limb conditions.
Providing clinicians and research workers with a potent therapeutic/prophylactic modality for disorders of the equine distal limb.
To assess the effects of external thermal manipulation on the soft-tissue and vascular perfusion of the equine digit using nuclear scintigraphy and documented tissue temperatures.
Six horses were used in a randomised crossover design. Each horse was treated with external heat (47 degrees C) or external cold (4 degrees C) applied to a digit for 30 minutes. The opposite front foot was untreated and used for control measurements. Nuclear scintigraphy was performed before, during, and after therapy to assess vascular and soft-tissue perfusion to the digit in response to therapy. Dorsal hoof wall laminar-tissue temperatures were recorded before, during, and after therapy using a thermistor.
Treatment with topical cold therapy significantly decreased soft-tissue perfusion of the digit to 80.5% of the pre-cooled values. Conversely, the application of external heat significantly increased soft-tissue perfusion of the digit 25.1% above the pre-heated values. Vascular perfusion showed similar, but not statistically significant trends. External cold application to the digit caused a significant mean decrease in laminar-tissue temperatures of 11.6 degrees C during therapy, while external heat application to the digit caused a significant mean increase in laminar-tissue temperatures of 3.9 degrees C.
The external application of heat and cold to the normal equine foot could effectively alter soft-tissue perfusion and laminar-tissue temperatures within 30 minutes of treatment. The application of hot water and ice water to the digit was a safe, well-tolerated, and economical therapy.
Cooling the foot could decrease enzymatic reactions associated with laminitis, and warming could increase local perfusion when desired.
The use of cryotherapy in equine sports medicine
- Blackwell
Blackwell RB: The use of cryotherapy in equine sports medicine. The Equine Athlete 4:1-5, 1991
Current concepts of inner hoof wall anatomy , physiology and pathophysiology, in Large Animal Proceedings of the Ninth Annual American College of Veterinary Surgeons Symposium Distal limb cryotherapy 69 5. van Eps AW, Pollitt CC: Equine laminitis: Cryotherapy reduces the severity of the acute lesion
- Cc Pollitt
- Equine
Pollitt CC: Equine laminitis: Current concepts of inner hoof wall anatomy, physiology and pathophysiology, in Large Animal Proceedings of the Ninth Annual American College of Veterinary Surgeons Symposium, San Francisco, pp 175-180, 1999 Distal limb cryotherapy 69 5. van Eps AW, Pollitt CC: Equine laminitis: Cryotherapy reduces the severity of the acute lesion. Equine Vet J 36:255-260, 2004
The phar-macologicbasisforthetreatmentofdevelopmentalandacutelaminitis
- Sumano Gw Brumbaugh
- Hoyas H Lopez
- Sepulveda
Brumbaugh GW, Sumano Lopez H, Hoyas Sepulveda ML: The phar-macologicbasisforthetreatmentofdevelopmentalandacutelaminitis. Vet Clin North Am Equine Pract 15:345-362, 1999