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ABSTRACT: Acute exposure to high altitude (HA) induces changes in CO membrane conductance (DmCO) and capillary lung volume (Vc). One source of scatter in literature data is exercise, climbing, prior to HA which was avoided in this study. Measurements were performed in 25 lowlanders at Brussels (D0) and at 4300 m after a 2 or 3 days exposure (D2,3), before and after an exercise test, and 5 days later (D7,8) under a trial with two arterial pulmonary vasodilators and a placebo group. The NO/CO transfer method was used applying either an infinite or a finite value to the NO blood conductance (θNO) which could alter sharply the results. A doppler echocardiography provided the haemodynamic data. Compared to sea level, DLCO increased by 24% at D2,3 and returned to control at D7,8. The increase in DLCO resulted from increases in DmCOand Vc whatever the θNO value The alveolar volume (VA) increased by 16% at D2,3 and normalized at D7,8. The mean increase in systolic arterial pulmonary pressure at rest at D2,3 was slight. The increase in Vc in acute condition might be due to the increase in VA and to the increase in capillary pressure. . Compared to the infinite θNO value, the use of a finite θNO value led to about a two-fold increase in DmCO value and to a persistent increase in DmCO at D7,8 compared to D0. After exercise DmCO decreased slightly in subjects treated by the vasodilators suggesting an effect on interstitial oedema.
Journal of Applied Physiology 04/2013; · 3.75 Impact Factor
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ABSTRACT: The time constant of the pulmonary circulation, or product of pulmonary vascular resistance (PVR) and compliance (Ca), called the RC-time, has been reported to remain constant over a wide range of pressures, etiologies of pulmonary hypertension, and treatments. We wondered whether increased wave reflection on proximal pulmonary vascular obstruction, like in operable chronic thromboembolic pulmonary hypertension (CTEPH), might also decrease the RC-time and thereby increase pulse pressure and right ventricular afterload. Pulmonary hypertension of variable severity was induced either by proximal obstruction (pulmonary arterial ensnarement) or distal obstruction (micro-embolism) in 8 anesthetized dogs. Pulmonary artery pressures (Ppa) were measured with high-fidelity micromanometer-tipped catheters, and pulmonary flow with transonic technology. Pulmonary ensnarement increased mean Ppa, PVR and characteristic impedance (ZC), decreased Ca and the RC-time (from 0.46 ± 0.07 to 0.30 ± 0.03 s) and increased the oscillatory component of hydraulic load (Wosc/Wtot) from 25 ± 2 to 29 ± 2 %. Pulmonary micro-embolism increased mean Ppa and PVR, with no significant change in Ca and ZC, increased RC-time from 0.53 ± 0.09 to 0.74 ± 0.05 s and decreased Wosc/Wtot from 26 ± 2 to 13 ± 2 %. Pulse pressure increased more after ensnarement than after microembolism. Concomitant measurements with fluid-filled catheters showed the same functional differences between the two types of pulmonary hypertension, with however an underestimation of Wosc. We conclude that pulmonary hypertension caused by proximal versus distal obstruction is associated with a decreased RC-time and an increased pulsatile component of right ventricular hydraulic load.
Journal of Applied Physiology 03/2013; · 3.75 Impact Factor
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ABSTRACT: BACKGROUND: The distance walked in 6 minutes (6MWD) has been reported to be linearly related to peak oxygen uptake (VO2) in cardiac diseases and in lung diseases. In these patients, the VO2 during a 6-min walk test (walkVO2) has been found to be nearly equivalent to peakVO2, but with a lower respiratory exchange ratio (RER). Whether these observations translate to the less functionally impaired patients or healthy control subjects is not exactly known. METHODS: Thirty-two healthy control subjects and 15 chronic heart failure (CHF) patients performed a 6-min walk test and a maximal cardiopulmonary exercise test (CPET) both with measurements of gas exchange. RESULTS: The 6MWD and peakVO2 were linearly correlated, but with an increased slope appearing above 532 m. In CHF patients, walkVO2 was similar to peakVO2, but with lower heart rate and ventilation than measured at peak exercise. In healthy control subjects, VO2, ventilation and heart rate were lower during the 6-min walk than at maximal exercise but higher than at the anaerobic threshold. The RER during the 6-min walk remained <1 in both groups. CONCLUSIONS: Above 500 m, 6MWD becomes less sensitive to any increase in peakVO2. Furthermore, CHF patients and healthy control subjects exercise respectively at maximal and high VO2, but below the anaerobic threshold (as assessed by a CPET) during the 6-min walk test.
European journal of preventive cardiology. 03/2013;
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ABSTRACT: Abstract Pavelescu, Adriana, Vitalie Faoro, Herve Guenard, Claire de Bisschop, Jean-Benoit Martinot, Christian Melot, Robert Naeije. Pulmonary vascular reserve and exercise capacity at sea level and at high altitude. High Alt. Med. Biol. 14:19-26, 2013.-It has been suggested that increased pulmonary vascular reserve, as defined by reduced pulmonary vascular resistance (PVR) and increased pulmonary transit of agitated contrast measured by echocardiography, might be associated with increased exercise capacity. Thus, at altitude, where PVR is increased because of hypoxic vasoconstriction, a reduced pulmonary vascular reserve could contribute to reduced exercise capacity. Furthermore, a lower PVR could be associated with higher capillary blood volume and an increased lung diffusing capacity. We reviewed echocardiographic estimates of PVR and measurements of lung diffusing capacity for nitric oxide (DLNO) and for carbon monoxide (DLCO) at rest, and incremental cardiopulmonary exercise tests in 64 healthy subjects at sea level and during 4 different medical expeditions at altitudes around 5000 m. Altitude exposure was associated with a decrease in maximum oxygen uptake (Vo2max), from 42±10 to 32±8 mL/min/kg and increases in PVR, ventilatory equivalents for CO2 (VE/Vco2), DLNO, and DLCO. By univariate linear regression Vo2max at sea level and at altitude was associated with VE/Vco2 (p<0.001), mean pulmonary artery pressure (mPpa, p<0.05), stroke volume index (SVI, p<0.05), DLNO (p<0.02), and DLCO (p=0.05). By multivariable analysis, Vo2max at sea level and at altitude was associated with VE/Vco2, mPpa, SVI, and DLNO. The multivariable analysis also showed that the altitude-related decrease in Vo2max was associated with increased PVR and VE/Vco2. These results suggest that pulmonary vascular reserve, defined by a combination of decreased PVR and increased DLNO, allows for superior aerobic exercise capacity at a lower ventilatory cost, at sea level and at high altitude.
High altitude medicine & biology 03/2013; 14(1):19-26. · 1.58 Impact Factor
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ABSTRACT: Exercise stresses the pulmonary circulation through increases in cardiac output and left atrial pressure. Invasive as well as non-invasive studies in healthy volunteers show that the slope of mean pulmonary artery pressure-flow relationships ranges from 0.5 to 3 mmHg.L.min-1. The upper limit of normal of mean pulmonary artery pressure at exercise thus approximates 30 mmHg at a cardiac output of less than 10 L.min-1, or a total pulmonary vascular resistance at exercise of less than 3 Wood units. Left atrial pressure increases at exercise with an average upstream transmission to pulmonary artery pressure in a close to one for one mmHg fashion. Multipoint pulmonary artery pressure-flow relationships are usually described by a linear approximation, but present with a slight curvilinearity which is explained by resistive vessel distensibility. When mean pulmonary artery pressure is expressed as a function of oxygen uptake or workload, plateau patterns may be observed in patients with systolic heart failure who cannot further increase cardiac output at the highest levels of exercise. Exercise has to be dynamic, to avoid the increase in systemic vascular resistance and abrupt changes in intrathoracic pressure that occur with resistive exercise and can lead to unpredictable effects on the pulmonary circulation. Post-exercise measurements are unreliable because of the rapid return of pulmonary vascular pressures and flows to the baseline resting state. Recent studies suggest that exercise-induced increase in pulmonary artery pressure to a mean higher than 30 mmHg may be associated with dyspnea-fatigue symptomatology.
American Journal of Respiratory and Critical Care Medicine 01/2013; · 11.08 Impact Factor
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Alexander Van De Bruaene,
Pieter De Meester,
Jens-Uwe Voigt,
Marion Delcroix,
Agnes Pasquet,
Julie De Backer,
Michel De Pauw, Robert Naeije,
Jean-Luc Vachiéry,
Bernard P Paelinck,
Marielle Morissens,
Werner Budts
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ABSTRACT: OBJECTIVES: To evaluate (1) changes in clinical, biochemical and echocardiographic parameters, (2) whether deterioration in exercise capacity and resting oxygen saturation (SatO2-rest) are related with adverse outcome and (3) its additional value in predicting outcome in Eisenmenger patients. METHODS: Seventy-seven (36±14years, 30% male) patients were included and prospectively followed. Changes between baseline and final visit were evaluated. Clinical deterioration was defined as a deterioration in exercise capacity or SatO2-rest. Univariate and multivariate analyses were performed to evaluate predictors of outcome defined as the need for hospitalization due to right heart failure, transplantation, or all-cause mortality. Finally, the additional prognostic value of deterioration in exercise capacity and SatO2-rest was evaluated. RESULTS: During a mean follow-up period of 4.0±2.1years, 27 (35%) events occurred. Patients in the event-group presented with an deterioration in NYHA class (P<0.0001), 6minute walk distance (P=0.006) and SatO2-rest (P<0.0001). After adjustment for baseline variables, multivariate Cox regression analysis indicated that clinical deterioration was independently associated with adverse outcome. CONCLUSIONS: Clinical deterioration, defined as a deterioration in exercise capacity or SatO2-rest was associated with adverse outcome in Eisenmenger patients. Moreover, these parameters provided additional information on which patients would develop an event and may benefit from initiation or escalation of disease targeting therapy.
International journal of cardiology 01/2013; · 7.08 Impact Factor
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European Respiratory Journal 01/2013; 41(1):7. · 5.89 Impact Factor
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ABSTRACT: Stroma cell-derived factor-1α (SDF-1α) is a cardioprotective chemokine, acting through its G-protein coupled receptor CXCR4. In experimental acute myocardial infarction, administration of SDF-1α induces an early improvement of systolic function which is difficult to explain solely by an anti-apoptotic and angiogenic effect. We wondered whether SDF-1α signaling might have direct effects on calcium transients and beating frequency.Primary rat neonatal cardiomyocytes were culture-expanded and characterized by immunofluorescence staining. Calcium sparks were studied by fluorescence microscopy after calcium loading with the Fluo-4 acetoxymethyl ester sensor. The cardiomyocyte enriched cellular suspension expressed troponin I and CXCR4 but was vimentin negative. Addition of SDF-1α in the medium increased cytoplasmic calcium release. The calcium response was completely abolished by using a neutralizing anti-CXCR4 antibody and partially suppressed and delayed by preincubation with an inositol triphosphate receptor (IPR) blocker, but not with a ryanodine receptor (RyR) antagonist. Calcium fluxes induced by caffeine, a RyR agonist, were decreased by an IPR blocker. Treatment with forskolin or SDF-1α increased cardiomyocyte beating frequency and their effects were additive. , treatment with SDF-1α increased left ventricular dP/dtmax.These results suggest that in rat neonatal cardiomyocytes, the SDF-1α/CXCR4 signaling increases calcium transients in an IP-gated fashion leading to a positive chronotropic and inotropic effect.
PLoS ONE 01/2013; 8(2):e56007. · 4.09 Impact Factor
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Ekkehard Grünig,
Philipp Henn,
Antonello D'Andrea,
Martin Claussen,
Nicola Ehlken,
Felicitas Maier, Robert Naeije,
Christian Nagel,
Felix Prange,
Johannes Weidenhammer,
Christine Fischer,
Eduardo Bossone
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ABSTRACT: BACKGROUND: -Right atrial (RA) size is important in screening, diagnosis and follow-up assessment in patients with pulmonary hypertension. The objective of this paper was to define normal reference values for RA area by echocardiography in a large population of athletic versus sedentary healthy subjects. METHODS AND RESULTS: -In the first part of the study 880 healthy adult subjects (mean age 28±6 years, 38% female, 395 top-level endurance athletes, 255 strength athletes and 230 non-athletes) were prospectively assessed. In the second part we performed a pooled analysis of all studies published between 1976 and 2011 describing RA area in healthy subjects (n=624). Statistical analysis included the calculation of 95% quantiles for defining cut-off values. Mean RA area in the 880 subjects was significantly larger in endurance athletes as compared to strength and non-athletes. RA area correlated significantly with age, gender, body surface and endurance training. In synopsis of both datasets 95% quantiles for RA-area in strength- and non-athletes were 15.2cm(2) (95% confidence interval 14.7-15.7cm(2)) in females and 16.2cm(2) (95% confidence interval 15.8-16.6cm(2)) in males. CONCLUSIONS: -To our knowledge, this is the largest data set to describe RA size in adult healthy subjects (aged below 50 years). Cut-off values for RA area were significantly different in females (15cm(2)) and males (16cm(2)). Age, gender, body surface area and high level endurance training were determinants of RA area.
Circulation Cardiovascular Imaging 11/2012; · 5.94 Impact Factor
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European Respiratory Journal 11/2012; 40(5):1287-9. · 5.89 Impact Factor
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ABSTRACT: In chronic thromboembolic pulmonary hypertension (CTEPH) increased pulmonary vascular resistance is caused by fibrotic organization of unresolved thromboemboli. CTEPH mainly differs from pulmonary arterial hypertension (PAH) by the proximal location of pulmonary artery obliteration, although distal arteriopathy can be observed as a consequence of non-occluded area overperfusion. Accordingly, there is proportionally more wave reflection in CTEPH, impacting on pressure and flow wave morphology. However, the time constant, that is resistance times compliance, is not different in CTEPH and PAH, indicating only trivial effects of proximal wave reflection on hydraulic right ventricular load. More discriminative is the analysis of the pressure decay after pulmonary arterial occlusion, which is more rapid in the absence of significant distal arteriopathy. Structure and function of the right ventricle show a similar pattern of right ventricular hypertrophy, namely dilatation and wall thickening as well as loss of function in CTEPH as in PAH. This is probably related to similar loading conditions. Hyperventilation with hypocapnia is characteristic of both PAH and CTEPH. Ventilatory equivalents for carbon dioxide, as a function of arterial PCO2, conform to the alveolar ventilation equation in both conditions, indicating a predominant role of increased chemosensitivity. However, a slight increase in the arterial to end-tidal PCO2 gradient in CTEPH shows a contribution of increased dead space ventilation.
European Respiratory Journal 08/2012; · 5.89 Impact Factor
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ABSTRACT: Key points Pulmonary transit of agitated contrast (PTAC) occurs during exercise in healthy individuals. It has been suggested that positive PTAC reflects a greater pulmonary vascular reserve, allowing for the right ventricle to operate at a decreased afterload at high levels of exercise. In this study, we determined whether individuals with highest maximal aerobic capacity have the greatest pulmonary vascular distensibility, highest PTAC and greatest increase in the capillary blood component of lung diffusing capacity during exercise. We observed that individuals with highest maximal aerobic capacity have a more distensible pulmonary circulation as observed through greater pulmonary vascular distensibility, greater pulmonary capillary blood volume, and lowest pulmonary vascular resistance at maximal exercise. Pulmonary vascular distensibility predicts aerobic capacity in healthy individuals.
The Journal of Physiology 06/2012; 590(Pt 17):4279-88. · 4.72 Impact Factor
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ABSTRACT: We tested the ability of exercise testing to predict not only survival but also time to clinical worsening in idiopathic versus associated pulmonary arterial hypertension (PAH).Hundred thirty-six patients with PAH (85 idiopathic and 51 with associated conditions), underwent cardiopulmonary exercise testing and a 6-minute walk test. Death or transplantation, and clinical worsening events were recorded.Thirty-two patients died and 4 had lung transplantation. At univariate analysis, PAH patients survival was associated with oxygen uptake (VO2) at peak exercise and at anaerobic threshold, ventilatory equivalent for CO2 (VEVCO2) at anaerobic threshold (at), VE/VCO2slope and distance walked. Time to clinical worsening was associated with peakVO2 and VO2at, VEVCO2at, end-tidal CO2 partial pressure measured at anaerobic threshold, peakO2 pulse, increase in O2pulse and distance walked. At multivariable analysis, distance walked and VEVCO2at predicted survival, and only peakVO2 predicted time to clinical worsening. The ROC curve-derived cut-off values were 305 m for the 6-min walk distance, 54 for VEVCO2at and 11.6 mL·Kg(-1).min for peakVO2. In the subgroup of associated PAH, no variable independently predicted survival or clinical worsening.We conclude several exercise variables predict survival and clinical stability in idiopathic PAH. Exercise variables are less accurate predictors of outcome in associated PAH.
European Respiratory Journal 03/2012; · 5.89 Impact Factor
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ABSTRACT: Little is known about molecular changes in lungs of fetal rabbits with surgically induced diaphragmatic hernia (DH). Therefore, we examined in this model gene expressions of pivotal molecules for the developing lung.
At day 23 of gestation, DH was created in 12 fetuses from 4 does. Both lungs from six live DH fetuses and from six unoperated controls were harvested and weighed at term. Transcription of 15 genes involved in alveolarization, angiogenesis, regulation of vascular tone, or epithelial maturation was investigated by real-time quantitative polymerase chain reaction.
DH decreased lung-to-body weight ratio (P < 0.001). A bilateral downregulation was seen for genes encoding for tropoelastin (P < 0.01), lysyl oxidase (P < 0.05), fibulin 5 (P < 0.05), and cGMP specific phosphodiesterase 5 (P < 0.05). Lower mRNA levels for endothelial nitric oxide synthase occurred in the ipsilateral lung (P < 0.05).
Experimental DH in fetal rabbits disrupted transcription of genes implicated in lung growth and function. Similarities with the human disease make this model appropriate for investigation of new prenatal therapies. Pediatr Pulmonol. 2012. 47:1088-1096. © 2012 Wiley Periodicals, Inc.
Pediatric Pulmonology 02/2012; 47(11):1088-96. · 2.53 Impact Factor
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Alexander Van De Bruaene,
Pieter De Meester,
Jens-Uwe Voigt,
Marion Delcroix,
Agnes Pasquet,
Julie De Backer,
Michel De Pauw, Robert Naeije,
Jean-Luc Vachiéry,
Bernard Paelinck,
Marielle Morissens,
Werner Budts
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ABSTRACT: To evaluate (1) whether right ventricular (RV) dysfunction, evaluated using tricuspid annular plane systolic excursion (TAPSE) is associated with a worse outcome in patients with the Eisenmenger syndrome, (2) which variables are related to RV dysfunction, and (3) whether differences exist among simple pretricuspid, simple post-tricuspid, and combined shunt lesions. Patients with Eisenmenger syndrome, aged >18 years, who underwent echocardiography, were selected from the Belgian Eisenmenger registry and prospectively followed up using a Web-based registry. Cox regression analysis was performed to evaluate the relation to outcomes, defined as all-cause mortality, transplantation, and hospitalization for cardiopulmonary causes. Comparative and bivariate analysis was performed, where applicable. A total of 58 patients (mean age 35.1 ± 13.2 years, 32.8% men) were included. During a mean follow-up of 3.2 years, 22 patients (37.9%) reached the predefined end point. Only TAPSE (hazard ratio 0.820, 95% confidence interval 0.708 to 0.950; p = 0.008) was related to the adverse outcomes on multivariate analysis. Patients with pretricuspid shunt lesions were older (p <0.0001) had greater left (p <0.0001) and right atrial (p <0.0001) dimensions, greater RV dimensions (p = 0.002), and more tricuspid regurgitation (p = 0.012) compared to patients with post-tricuspid lesions. Lower TAPSE was related to the presence of pulmonary artery thrombosis (R = -0.378; p = 0.006). In conclusion, in patients with Eisenmenger syndrome, RV dysfunction, evaluated using TAPSE, is related to worse outcomes. Patients with Eisenmenger syndrome with pretricuspid shunt lesions were older and had greater left atrial, right atrial, and RV dimensions compared to patients with post-tricuspid lesions, indicating a difference in the RV response. Lower TAPSE was associated with the presence of pulmonary artery thrombosis.
The American journal of cardiology 01/2012; 109(8):1206-11. · 3.58 Impact Factor
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ABSTRACT: Lung diffusing capacity has been reported variably in high-altitude newcomers and may be in relation to different pulmonary vascular resistance (PVR). Twenty-two healthy volunteers were investigated at sea level and at 5,050 m before and after random double-blind intake of the endothelin A receptor blocker sitaxsentan (100 mg/day) vs. a placebo during 1 wk. PVR was estimated by Doppler echocardiography, and exercise capacity by maximal oxygen uptake (Vo(2 max)). The diffusing capacities for nitric oxide (DL(NO)) and carbon monoxide (DL(CO)) were measured using a single-breath method before and 30 min after maximal exercise. The membrane component of DL(CO) (Dm) and capillary volume (Vc) was calculated with corrections for hemoglobin, alveolar volume, and barometric pressure. Altitude exposure was associated with unchanged DL(CO), DL(NO), and Dm but a slight decrease in Vc. Exercise at altitude decreased DL(NO) and Dm. Sitaxsentan intake improved Vo(2 max) together with an increase in resting and postexercise DL(NO) and Dm. Sitaxsentan-induced decrease in PVR was inversely correlated to DL(NO). Both DL(CO) and DL(NO) were correlated to Vo(2 max) at sea level (r = 0.41-0.42, P < 0.1) and more so at altitude (r = 0.56-0.59, P < 0.05). Pharmacological pulmonary vasodilation improves the membrane component of lung diffusion in high-altitude newcomers, which may contribute to exercise capacity.
Journal of Applied Physiology 01/2012; 112(1):20-5. · 3.75 Impact Factor
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ABSTRACT: Sildenafil and epoprostenol are effective therapies in pulmonary arterial hypertension (PAH). Both drugs increase cardiac output, which has been in part attributed to improved right ventricular (RV) contractility. We therefore used tissue Doppler imaging (TDI) to test whether sildenafil and epoprostenol might differently affect RV function in normal subjects before and after induction of acute hypoxic pulmonary hypertension. Ten healthy volunteers underwent this randomized, double-blind, placebo-controlled cross-over study. Echocardiographic measurements were obtained 60 min after the intake of a placebo or 50 mg sildenafil or under 8 ng/kg/min iv epoprostenol, in normoxia or after 60 min of hypoxic breathing (FIO(2) of 0.12). Right ventricular systolic function was assessed by systolic strain (ε), strain rate (SR), isovolumic contraction acceleration (IVA) and tricuspid annulus plane systolic excursion (TAPSE), and diastolic function by tricuspid annulus E/A ratio and isovolumic relaxation time related to RR interval (IRT/RR). Pulmonary artery pressure was calculated from the acceleration time of pulmonary flow and cardiac output from the left ventricular outflow tract flow-velocity. Hypoxia increased pulmonary vascular resistance (PVR) by 78%, did not affect indices of RV systolic function, decreased E/A and increased IRT/RR. Epoprostenol more than sildenafil increased cardiac output, apical ε and TAPSE, the latter in proportion to decreased PVR. In addition, apical SR was increased only by epoprostenol. None of the drugs affected IVA, basal SR, E/A and IRT/RR. These results are not suggestive of intrinsic positive inotropic effects of either sildenafil or epoprostenol at maximal doses tolerated by normal subjects.
Arbeitsphysiologie 07/2011; 112(4):1285-94. · 2.15 Impact Factor
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ABSTRACT: Three-month chronic systemic-to-pulmonary shunting in growing piglets has been reported as an early pulmonary arterial hypertension (PAH) model with preserved right ventricular (RV) function. We sought to determine whether prolonged shunting might be associated with more severe PAH and RV failure.
Fourteen growing piglets were randomized to a sham operation or the anastomosis of the left innominate artery to the pulmonary arterial trunk. Six months later, the shunt was closed and the animals underwent haemodynamic evaluation followed by tissue sampling for pathobiological assessment. Prolonged shunting had resulted in increased mean pulmonary artery pressure (22 ± 2 versus 17 ± 1 mmHg) and pulmonary arteriolar medial thickness, while cardiac output was decreased. However, RV-arterial coupling was markedly deteriorated, with a ~50% decrease in the ratio of end-systolic to pulmonary arterial elastances (Ees/Ea). Lung tissue expressions of endothelin-1, angiopoietin-1, and bone morphogenetic protein receptor-2 were similarly altered compared with previously observed after 3-month shunting. At the RV tissue level, pro-apoptotic ratio of Bax-to-Bcl-2 expressions and caspase-3 activation were increased, along with an increase in cardiomyocyte size, while expressions in voltage-gated potassium channels (Kv1.5 and Kv2.1) and angiogenic factors (angiopoietin-2 and vascular endothelial growth factor) were decreased. Right ventricular expressions of pro-inflammatory cytokines [interleukin (IL)-1α, IL-1β, tumour necrosis factor-α (TNF-α)] and natriuretic peptide precursors (NPPA and NPPB) were increased. There was an inverse correlation between RV Ees/Ea and pro-apoptotic Bax/Bcl-2 ratios.
Prolonged left-to-right shunting in piglets does not further aggravate pulmonary vasculopathy, but is a cause of RV failure, which appears related to an activation of apoptosis and inflammation.
European Heart Journal 05/2011; 33(8):1017-26. · 10.48 Impact Factor
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ABSTRACT: Iron deficiency is common in patients with Eisenmenger syndrome (ES). This study aimed at evaluating (i) whether iron deficiency is related with adverse outcome, (ii) the determinants of iron deficiency, and (iii) the relation between iron reserves and haemoglobin level in a contemporary cohort of ES patients.
All ES patients, older than 18 years, selected from the Belgian Eisenmenger registry, were prospectively followed using a web-based registry. Univariate Cox-regression analysis was performed to evaluate the relation with outcome, defined as all-cause mortality, transplantation, and hospitalisation due to cardiopulmonary causes. Bivariate analysis was performed where applicable. A total of 68 patients with a complete dataset (mean age 36.9 ± 14.2 years; 30.9% male) were included. During a median follow-up time of 3.1 years, 21 patients (30.9%) reached the predefined endpoint. New York Heart Association (NYHA) class ≥ III (HR 4.76; 95% CI 1.84-12.30; P = 0.001), iron deficiency (HR 5.29; 95% CI 2.04-13.76; P = 0.001), mean corpuscular volume (MCV) (HR 0.94; 95% CI 0.90-0.99; P = 0.021), and mean corpuscular haemoglobin (MCH) (HR 0.87; 95% CI 0.76-0.98; P = 0.027) were related with adverse outcome. The use of oral anticoagulation and frequent phlebotomies were independently related with iron deficiency (P = 0.005 and P = 0.008). In iron-deplete patients, MCV (R = -0.408; P= 0.014) and MCH (R = -0.437; P = 0.026) were inversely related with haematocrit. In patients with low oxygen saturation, iron reserves were related with haemoglobin levels (R = 0.587; P = 0.001).
Iron deficiency was associated with a higher risk of adverse outcome. Moreover, the use of oral anticoagulation OAC and frequent phlebotomies were related to iron deficiency. Patients under anticoagulation should be monitored rigorously for iron deficiency. However, in patients with low oxygen saturations, careful iron substitution to avoid too high haemoglobin levels is suggested.
European Heart Journal 05/2011; 32(22):2790-9. · 10.48 Impact Factor
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ABSTRACT: Because of the challenges associated with conducting large survival studies of patients with pulmonary arterial hypertension (PAH), we analyzed the surrogate markers predictive of long-term survival in a large cohort of patients treated with subcutaneous treprostinil.
A retrospective review was conducted using data from a total of 811 patients with New York Heart Association Functional Class (NYHA FC) II to IV PAH, who were treated with subcutaneous treprostinil. Patient baseline disease and on-treatment parameters were analyzed by uni- and multivariate analyses for predictive value of 3-year survival with PAH.
Among the baseline disease-related factors analyzed, there was a significantly higher risk of death (p < 0.001) associated with connective tissue disease-associated PAH relative to idiopathic PAH (hazard ratio for death [HR] 1.93), NYHA FC IV vs III (HR 2.31), pulmonary vascular resistance index (PVRI) >30 vs ≤16 mm Hg/liter/min/m(2) (HR 2.44) and mixed venous oxygen saturation (SVO(2)) ≤55% vs >55%. The 6-minute walk distance (6MWD) of ≤295 m after 12 weeks of treprostinil treatment was associated with reduced survival at 3 years (58%). A ≥20-m increase from baseline in 6MWD was associated with greater survival (80%) vs smaller walk increments (69%; p = 0.039). Treprostinil dose of ≥40 ng/kg/min (p < 0.001) and every 10-ng/kg/min dose increase (p = 0.009) resulted in improved long-term survival. In a multivariate analysis, only SVO(2), 6MWD and treprostinil dose were significant on-treatment predictors (p < 0.02) of survival.
Disease etiology, baseline factors (NYHA FC, PVRI and SVO(2)) and on-treatment factors (6MWD, SVO(2) and treprostinil dose) were predictors of survival in this study and may be used to aid in treatment optimization.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 04/2011; 30(9):982-9. · 3.54 Impact Factor
