Publications (38)238.87 Total impact
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Article: PROXIMAL PULMONARY ARTERIAL OBSTRUCTION DECREASES THE TIME CONSTANT OF THE PULMONARY CIRCULATION AND INCREASES RIGHT VENTRICULAR AFTERLOAD.
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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 -
Article: Hypertonic saline hydroxyethylstarch restores right ventricular-arterial coupling after normovolemic hemodilution in piglets.
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ABSTRACT: Normovolemic hemodilution is known to inhibit hypoxic pulmonary vasoconstriction. How the coupling between the pulmonary arterial (PA) circulation and the right ventricle (RV) is affected by normovolemic hemodilution and by the composition of replacement solutions remains unknown. Therefore, the effects of isotonic and hypertonic saline hydroxyethylstarch solutions on the pulmonary circulation and RV, in control and hypoxic conditions, were compared. Anesthetized piglets (n = 14) were equipped with manometer-tipped catheters in the RV and main PA and an ultrasonic flow probe around the main PA. The pulmonary circulation was assessed by pressure-flow relations and vascular impedance, RV afterload by effective arterial elastance (Ea), RV contractility by end-systolic elastance (Ees), and RV-PA coupling by the Ees/Ea ratio. Measurements were done in control (Fio2 0.40) and hypoxic (Fio2 0.12) conditions before and after acute normovolemic hemodilution with either 20 ml/kg isotonic saline hydroxyethylstarch (hydroxyethylstarch 130/0.4 6% in NaCl 0.9%, Voluven, Fresenius-Kabi, Sevres, France) or 5 ml/kg hypertonic saline hydroxyethylstarch (hydroxyethylstarch 200/0.5 6% in NaCl 7.2%, HyperHES, Fresenius-Kabi) solutions. Hypoxic pulmonary vasoconstriction was associated with proportional increases in Ea and Ees and did not affect RV-PA coupling. Hemodilution attenuated the hypoxic response. Hemodilution with isotonic saline hydroxyethylstarch did not affect the RV-PA coupling, whereas hemodilution with hypertonic saline hydroxyethylstarch increased Ees and the Ees/Ea ratio. In experimental normovolemic hemodilution, both in control and in hypoxic conditions, RV-PA coupling is unaffected by isotonic saline hydroxyethylstarch but improved by hypertonic saline hydroxyethylstarch, mainly because of an increase in RV contractility.Anesthesiology 07/2011; 115(1):136-43. · 5.36 Impact Factor -
Article: Prolonged overcirculation-induced pulmonary arterial hypertension as a cause of right ventricular failure.
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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 -
Article: Acute pulmonary embolism decreases adenosine plasma levels in anesthetized pigs.
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ABSTRACT: Adenosine plays a role in pulmonary arterial (PA) resistance due to its vasodilator properties. However, the behavior of adenosine plasma levels (APLs) during pulmonary embolism remains unknown. We investigated the effects of gradual pulmonary embolism on right ventricular (RV) contractility and PA coupling and on APLs in an piglet experimental model of RV failure. PA distal resistance by pressure-flow relationships and pulmonary vascular impedance were measured. RV contractility was determined by the end-systolic pressure-volume relationship (Ees), PA effective elastance by the end-diastolic to end-systolic relationship (Ea), and RV-PA coupling efficiency by the Ees/Ea ratio. APLs were measured before and during gradual pulmonary embolization. PA embolism increased PA resistance and elastance, increased Ea from 1.08 ± 0.15 to 5.62 ± 0.32 mmHg/mL, decreased Ees from 1.82 ± 0.10 to 1.20 ± 0.23 mmHg/mL, and decreased Ees/Ea from 1.69 ± 0.15 to 0.21 ± 0.07. APLs decreased from 2.7 ± 0.26 to 1.3 ± 0.12 μM in the systemic bed and from 4.03 ± 0.63 to 2.51 ± 0.58 μM in the pulmonary bed during embolism procedure. Pulmonary embolism worsens PA hemodynamics and RV-PA coupling. APLs were reduced, both in the systemic and in the pulmonary bed, leading then to pulmonary vasoconstriction.ISRN cardiology. 01/2011; 2011:750301. -
Article: Early right ventriculo-arterial uncoupling in borderline pulmonary hypertension on experimental heart failure.
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ABSTRACT: Pulmonary hypertension on heart failure (HF) limits exercise capacity and survival probably because of associated right ventricular (RV) failure. This study investigated the mechanisms of RV function adaptation to early pulmonary hypertension in experimental HF. Seven weeks of rapid ventricular pacing in six dogs induced a HF characterized by cardiomegaly and decreased left ventricular ejection fraction. Compared with eight control dogs, pulmonary hypertension was borderline, with a mean pulmonary artery pressure increased to only 23 ± 2 (means ± SE) mmHg. However, the pulmonary vascular impedance spectrum was globally shifted to higher pressures, with an increase in 0 Hz impedance (resistance) to 662 ± 69 vs. 455 ± 41 dynes·cm(-5)·m(2) in controls (P < 0.01) and in characteristic impedance to 183 ± 20 vs. 104 ± 7 dynes·cm(-5)·m(2) in controls (P < 0.01). There was no change in RV end-systolic elastance (Ees), but arterial elastance (Ea) was increased to 1.8 ± 0.3 vs. 0.9 ± 0.1 mmHg/ml in controls so that RV-arterial coupling defined by the Ees-to-Ea ratio (Ees/Ea) was decreased to 0.8 ± 0.1 vs. 1.5 ± 0.1 in controls (P < 0.01). Inhaled nitric oxide, 40 ppm or 5 μg·kg(-1)·min(-1) nitroprusside i.v., did not affect Ees/Ea. Fifty milligrams (i.v.) of milrinone increased Ees/Ea to 1.6 ± 0.2 by an isolated increase in Ees. We conclude that overpacing-induced HF is accompanied by a borderline pulmonary hypertension but profound RV-arterial uncoupling explained by the failure of RV systolic function to adapt combined effects of increased pulmonary arterial resistance and elastance.Journal of Applied Physiology 10/2010; 109(4):1080-5. · 3.75 Impact Factor -
Article: Sildenafil added to sitaxsentan in overcirculation-induced pulmonary arterial hypertension.
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ABSTRACT: Experimental left-to-right shunt-induced pulmonary arterial hypertension (PAH) can be partially prevented by the endothelin-A receptor blocker sitaxsentan or by the phosphodiesterase-5 inhibitor sildenafil. We hypothesized that the combined administration of these drugs would completely prevent shunt-induced PAH, arguing in favor of a major role of endothelial dysfunction in the initiation of the disease. Twenty-four 3-wk-old piglets were randomized to a sham operation or to placebo, sitaxsentan therapy, or sitaxsentan combined with sildenafil after the anastomosis of the left subclavian artery to the pulmonary arterial trunk. Three months later, the animals underwent a hemodynamic evaluation, followed by pulmonary tissue sampling for morphometry and quantitative real-time PCR for endothelin-1, angiopoietin-1, and bone morphogenetic protein receptor (BMPR) signaling molecules. Three months of left-to-right shunting induced an increase in pulmonary vascular resistance (PVR) and medial thickness, an overexpression of endothelin-1, and angiopoietin-1 and decreased expressions of BMPR-2 and BMPR-1A. Sitaxsentan partially prevented a shunt-induced increase in PVR, medial thickness, and associated biological disturbances. Sildenafil combined with sitaxsentan normalized PVR, medial thickness, and the expression of endothelin-1. However, the expression of angiopoietin-1 remained increased, and the expressions of BMPR-1A and BMPR-2 were incompletely returned to normal. The coupling of right ventricular end-systolic to arterial elastances was maintained in all circumstances. Sitaxsentan combined with sildenafil prevents shunt-induced PAH more effectively than sitaxsentan alone, suggesting a major role for the targeted signaling pathways in the initiation of the disease. Sitaxsentan alone or combined with sildenafil did not affect right ventricular function.AJP Heart and Circulatory Physiology 10/2010; 299(4):H1118-23. · 3.71 Impact Factor -
Article: Activation of apoptotic pathways in experimental acute afterload-induced right ventricular failure.
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ABSTRACT: The pathobiology of persistent right ventricular failure observed after an acute increase in right ventricular afterload remains incompletely understood. We hypothesized that persistent right ventricular dysfunction might be related to activation of apoptotic pathways. Prospective, randomized, controlled animal study. University research laboratory. Mongrel dogs. Fourteen anesthetized dogs were randomized to a transient 90-min pulmonary artery constriction operation to induce persistent right ventricular failure or to a sham operation followed 30 mins later by hemodynamic measurements and sampling of cardiac tissue. We evaluated effective arterial elastance to estimate right ventricular afterload and end-systolic elastance to estimate right ventricular contractility. Transient increase in pulmonary artery pressure persistently increased effective arterial elastance from 0.75 +/- 0.08 to 1.37 +/- 0.18 mm Hg/mL and decreased end-systolic elastance from 1.06 +/- 0.09 to 0.49 +/- 0.09 mm Hg/mL, end-systolic elastance/effective arterial elastance from 1.44 +/- 0.06 to 0.34 +/- 0.03, and cardiac output from 3.78 +/- 0.16 to 1.46 +/- 0.10 L/min, indicating right ventricular failure. At the pathobiologic level, we assessed apoptosis by real-time quantitative polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay, and immunohistochemistry. As compared with the sham-operated group, and with the left ventricle in animals with persistent right ventricular failure, there were decreased right ventricular and septal expressions of Bcl-2 with no changes in expressions of Bax, resulting in an increased Bax/Bcl-2 ratio. Right ventricular and septal Bcl-XL, and right ventricular Bcl-w gene expressions were decreased as compared with the sham-operated group, whereas Bak gene expression did not change. There were activations of right ventricular caspases-8 and -9 and of right ventricular and septal caspase-3. Diffuse right ventricular and septal apoptosis was confirmed by terminal deoxynucleotidyl transferase dUTP nick-end labeling staining. There were also increased right ventricular and septal protein expressions of tumor necrosis factor-alpha. Acute afterload-induced persistent right ventricular failure appears to be related to an early activation of apoptotic pathways and to a local overexpression of tumor necrosis factor-alpha, a proinflammatory cytokine.Critical care medicine 06/2010; 38(6):1405-13. · 6.37 Impact Factor -
Article: Ventricular-arterial uncoupling in heart failure with preserved ejection fraction after myocardial infarction in dogs - invasive versus echocardiographic evaluation.
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ABSTRACT: Heart failure with preserved left ventricular ejection fraction and abnormal diastolic function is commonly observed after recovery from an acute myocardial infarction. The aim of this study was to investigate the physiopathology of heart failure with preserved ejection fraction in a model of healed myocardial infarction in dogs. Echocardiography, levels of neurohormones and conductance catheter measurements of left ventricular pressure-volume relationships were obtained in 17 beagle dogs 2 months after a coronary artery ligation, and in 6 controls. Healed myocardial infarction was associated with preserved echocardiographic left ventricular ejection fraction (0.57 +/- 0.01, mean +/- SEM) and altered Doppler mitral indices of diastolic function. NT-proBNP was increased, aldosterone was decreased, and norepinephrine was unchanged. Invasive measurements showed a markedly decreased end-systolic elastance (2.1 +/- 0.2 vs 6.1 +/- 0.8, mmHg/ml, p < 0.001) and end-systolic elastance to effective arterial elastance ratio (0.6 +/- 0.1 vs 1.4 +/- 0.2, p < 0.001), with altered active relaxation (dP/dtmin -1992 +/- 71 vs -2821 +/- 305, mmHg/s, p < 0.01) but preserved left ventricular capacitance (70 +/- 6 vs 61 +/- 3, ml at 20 mmHg, p = NS) and stiffness constant. Among echocardiographic variables, the wall motion score index was the most reliable indicator of cardiac contractility while E', E/A and E'/A' were correlated to dP/dtmin. In the canine model of healed myocardial infarction induced by coronary ligation, heart failure is essentially characterized by an altered contractility with left ventricular-arterial uncoupling despite vascular compensation rather than by abnormal diastolic function.BMC Cardiovascular Disorders 01/2010; 10:32. · 1.52 Impact Factor -
Article: Bosentan decreases pulmonary vascular resistance and improves exercise capacity in acute hypoxia.
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ABSTRACT: Altitude exposure is associated with mild pulmonary hypertension and decreased exercise capacity. We tested the hypothesis that pulmonary vascular resistance (PVR) contributes to decreased exercise capacity in hypoxic healthy subjects. An incremental cycle ergometer cardiopulmonary exercise test and echocardiographic estimation of pulmonary artery pressure (Ppa) and cardiac output to calculate total PVR were performed in 11 healthy volunteers in normoxia and after 1 h of hypoxic breathing (12% O(2)). The measurements were performed in a random order at 1-week intervals after the receiving either a placebo or bosentan, following a double-blind randomized crossover design. Bosentan was administered twice a day for 3 days, 62.5 mg on the first day and 125 mg on the next 2 days. Hypoxic breathing decreased the mean (+/- SE) pulse oximetric saturation (Spo(2)) from 99 +/- 1% to 3 +/- 1% and increased the mean PVR from 5.6 +/- 0.3 to 7.2 +/- 0.5 mm Hg/L/min/m(2), together with a decrease in mean maximum O(2) uptake (Vo(2)max) from 47 +/- 2 to 35 +/- 2 mL/kg/min. Bosentan had no effect on normoxic measurements and did not affect hypoxic Spo(2), but decreased PVR to 5.6 +/- 0.3 mm Hg/L/min/m(2) (p < 0.01) and increased Vo(2)max to 39 +/- 2 mL/kg/min (p < 0.01) in hypoxia. Bosentan therapy, on average, restored 30% of the hypoxia-induced decrease in Vo(2)max. Bosentan-induced changes in Ppa and Vo(2)max were correlated (p = 0.01). We conclude that hypoxic pulmonary hypertension partially limits exercise capacity in healthy subjects, and that bosentan therapy can prevent it.Chest 02/2009; 135(5):1215-22. · 5.25 Impact Factor -
Article: ARDS: a clinicopathological confrontation.
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ABSTRACT: The heterogeneity of populations meeting criteria for ARDS may explain in part why no specific treatment has yet been shown to decrease mortality. To define the pathologic alterations associated with the syndrome, particularly the typical pattern of diffuse alveolar damage (DAD), and to evaluate whether etiologies or precipitating factors were missed, we evaluated patients who died with a clinical diagnosis of ARDS and who had a postmortem examination. We conducted a 3-year (2002 to 2004) review of all patients with ARDS (using the American-European Consensus Conference criteria) who died in our ICU and had a postmortem examination. Discrepancies between antemortem and postmortem diagnoses were classified as major and minor using the Goldman classification. Of 9,184 hospital admissions, 376 patients had a clinical diagnosis of ARDS. Of these, 169 died; 69 had a postmortem examination, and 64 of these had complete data for analysis. The main cause of death was multiple organ failure (27 of 64 patients). Postmortem examination revealed DAD in 32 patients (50%), pneumonia without DAD in 16 patients (25%), and invasive pulmonary aspergillosis in 8 patients (12.5%). Major unexpected findings were found in 15 patients (23%): 7 Goldman class I (including 4 cases of invasive pulmonary aspergillosis and 1 of disseminated tuberculosis) and 8 Goldman class II. In this study, ARDS remains a heterogeneous syndrome because only half of patients with ARDS had typical DAD. Open lung biopsy, if performed, might have led to appropriate therapy and potentially better outcome in five of the patients.Chest 01/2009; 135(4):944-9. · 5.25 Impact Factor -
Article: Activin-A, transforming growth factor-beta, and myostatin signaling pathway in experimental dilated cardiomyopathy.
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ABSTRACT: The pathogenic mechanisms of dilated cardiomyopathy are still uncertain. A number of cytokines and growth factors participate in the remodeling process of the disease. We investigated the cardiac myostatin, transforming growth factor (TGF)beta, and activin-A/Smad growth inhibitory signaling pathway in experimental dilated cardiomyopathy. Transvenous endomyocardial biopsies of the interventricular septum were taken weekly in 15 beagle dogs during the development of heart failure (HF) induced by rapid pacing over a period of 7 weeks. Genes involved in the myostatin-TGFbeta-activin-A/Smad signaling pathway and the cardiac hypertrophic process were quantified by real-time quantitative polymerase chain reaction. Left ventricular volume, function, and mass were evaluated by echocardiography. Overpacing was associated with increased left ventricular volumes and decreased ejection fraction, whereas the left ventricular mass remained unchanged. TGFbeta was increased in moderate HF. Activin-A mRNA expression was 4-fold higher in overt congestive HF than at baseline. A 2-fold decrease of activin type II receptors and activin receptor interacting protein 2 gene expressions were observed, as well as a transient decrease of follistatin. Activin type I receptors, activin receptor interacting protein 1, follistatin-related gene, and myostatin remained unchanged. The inhibitory Smad 7, a negative feedback loop regulator of the Smad pathway, was overexpressed in severe HF. Gene expression of the cyclin-dependent kinase inhibitor p21, a direct target gene of the Smad pathway, was 8-fold up-regulated in HF, whereas cyclin D1 was down-regulated. We conclude that tachycardia-induced dilated cardiomyopathy is characterized by gene overexpression of the TGFbeta-activin-A/Smad signaling pathway and their target gene p21 and by the absence of ventricular hypertrophy.Journal of cardiac failure 11/2008; 14(8):703-9. · 3.25 Impact Factor -
Article: Hyponatremia in neurological patients: cerebral salt wasting versus inappropriate antidiuretic hormone secretion.
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ABSTRACT: To assess whether hyponatremia in acute neurological patients is associated with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or with the cerebral salt-wasting syndrome (CSWS). Clinical, controlled, prospective study. Department of intensive care of a tertiary care academic hospital. Forty acute neurological patients with hyponatremia suggesting SIADH or CSWS (20) or with normonatremia (20). None. Measurement of clinical and biological variables. Measurement of blood, plasma, and red blood cell volumes to discriminate SIADH and CSWS. Renal, adrenal and thyroid functions were normal in all patients. Average blood, plasma, and red blood cell volumes were 54, 37 and 17ml/kg in control patients and 54, 37 and 18ml/kg in hyponatremic patients, respectively. The adequate blood volumes in hyponatremic patients confirm the diagnosis of SIADH and do not support the concept of CSWS.Intensive Care Medicine 02/2008; 34(1):125-31. · 5.40 Impact Factor -
Article: Tissue Doppler imaging evaluation of cardiac adaptation to severe pulmonary hypertension.
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ABSTRACT: Tissue Doppler imaging (TDI) was used to obtain additional insight into the cardiac adaptation to severe pulmonary arterial hypertension. Pulmonary hemodynamics and right and left ventricular function were investigated in 18 untreated patients, 12 with pulmonary arterial hypertension and 6 with chronic thromboembolic pulmonary hypertension. Fourteen age-matched healthy subjects served as controls for TDI measurements. Pulsed TDI was determined using atrioventricular planes and strain and strain rate along the right ventricular free wall, ventricular septum, and left ventricular lateral wall from 4-chamber apical views. Patients had early diastolic dysfunction, with decreased E-wave peak velocity and increased isovolumic relaxation time, both more important in the right than left ventricle. Compared with controls, strain and strain rate decreased along the right ventricular free wall with a midapical predominance (midbasal strain rate 1.7 +/- 0.6 vs 2.2 +/- 0.5; p = 0.02; midapical strain rate 0.9 +/- 0.9 vs 2.3 +/- 0.7; p <0.001), but were preserved along the left ventricular lateral wall. Tricuspid E-wave and isovolumic relaxation time (R = 0.62, p = 0.006), as well as midapical (r = 0.65, p = 0.004), but not midbasal, right ventricular strain and strain rate correlated with mean pulmonary artery pressures. In conclusion, cardiac function was abnormal in patients with severe pulmonary hypertension because of a combination of alterations in both diastolic and systolic right ventricular function and left ventricular diastolic function. Only right ventricular dysfunction correlated with pulmonary artery pressures.The American Journal of Cardiology 11/2007; 100(9):1473-8. · 3.37 Impact Factor -
Article: Effects of levosimendan on acute pulmonary embolism-induced right ventricular failure.
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ABSTRACT: Repeated episodes of pulmonary embolism can persistently increase pulmonary arterial pressure and depress right ventricular contractility. We investigated the effects of levosimendan on right ventricular-pulmonary arterial coupling in this model of right ventricular failure. Prospective, controlled, randomized animal study. University research laboratory. Fourteen anesthetized piglets. Repeated acute pulmonary embolisms were induced with autologous blood clots to induce persistent right ventricular failure. Animals were randomly assigned to a control or levosimendan group. Levosimendan 20 microg/kg was administered in 10 mins followed by 0.2 microg/kg/min or same volumes of isotonic saline. Pulmonary artery distal resistance and proximal elastance by pressure-flow relationships and vascular impedance were measured. We noted right ventricle contractility by the end-systolic pressure-volume relationship (Ees), pulmonary artery effective elastance by the end-diastolic to end-systolic relationship (Ea), and right ventricular-pulmonary arterial coupling efficiency by the Ees/Ea ratio. The gradual pulmonary artery embolism increased pulmonary artery resistance and elastance, increased Ea from 1.01 +/- 0.17 to 5.58 +/- 0.37 mm Hg/mL, decreased Ees from 1.75 +/- 0.12 to 1.29 +/- 0.20 mm Hg/mL, and decreased Ees/Ea from 1.74 +/- 0.20 to 0.24 +/- 0.09. Compared with placebo, levosimendan decreased pulmonary arterial elastance and characteristic impedance. Right ventricular-pulmonary arterial coupling was restored by both an increase in right ventricular contractility and a decrease in right ventricular afterload. A gradual increase in pulmonary artery pressure induced by pulmonary embolism persistently worsens pulmonary artery hemodynamics, right ventricular contractility, right ventricular-pulmonary arterial coupling, and cardiac output. Levosimendan restores right ventricular-pulmonary arterial coupling better than placebo, because of combined pulmonary vasodilation and increased right ventricular contractility.Critical Care Medicine 09/2007; 35(8):1948-54. · 6.33 Impact Factor -
Article: How prostacyclin improves cardiac output in right heart failure in conjunction with pulmonary hypertension.
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ABSTRACT: Prostacyclin therapy improves patients with pulmonary arterial hypertension, but whether this is attributable to an improved inotropic state of the right ventricle in addition to a decreased pulmonary arterial pulmonary vascular resistance remains unclear. We measured the effects of prostacyclin on load-independent measurements of right ventricular contractility in a model of load-induced acute right ventricular failure. Persistent right ventricular failure was induced in dogs by a transient (90 min) pulmonary arterial constriction. After constriction release and stabilization, intravenous prostacyclin (epoprostenol) was given at doses of 6 and 12 ng/kg/minute for 30 minutes. Pulmonary vascular resistance was assessed by pressure-flow relationships and right ventricular afterload by effective pulmonary arterial elastance. Right ventricular contractility was estimated by end-systolic elastance and right ventriculoarterial coupling efficiency by the ratio of these elastances. Transient pulmonary arterial constriction persistently increased pulmonary vascular resistance, increased arterial elastance from 1.00 +/- 0.07 to 2.86 +/- 0.26 mm Hg/ml, decreased end-systolic elastance from 1.11 +/- 0.07 to 0.54 +/- 0.02 mm Hg/ml, decreased the ratio of elastances from 1.14 +/- 0.08 to 0.20 +/- 0.02, and cardiac output from 4.6 +/- 0.1 to 2.3 +/- 0.1 L/min (p < 0.05). Epoprostenol did not affect end-systolic elastance; however, it decreased arterial elastance to 1.84 +/- 0.33 mm Hg/ml, and increased the ratio of elastances to 0.46 +/- 0.17 and cardiac output to 3.4 +/- 0.3 L/min (p < 0.05). In this model of afterload-induced right ventricular failure, prostacyclin improves right ventriculoarterial coupling and cardiac output because of vasodilating effects.American Journal of Respiratory and Critical Care Medicine 04/2007; 175(8):846-50. · 11.08 Impact Factor -
Article: Effects of levosimendan versus dobutamine on pressure load-induced right ventricular failure.
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ABSTRACT: A transient increase in pulmonary arterial (PA) pressure can persistently depress right ventricular (RV) contractility. We investigated the effects of dobutamine and levosimendan on RV-PA coupling in this model of RV failure. Prospective, controlled, randomized animal study. University research laboratory. Fifteen anesthetized dogs. Transient (90-min) PA constriction to induce persistent RV failure. Random assignment to dobutamine 5 and 10 microg/kg/min or levosimendan 12 microg/kg for 10 mins followed by 0.1 and 0.2 microg/kg/min. We measured PA distal resistance and proximal elastance by pressure-flow relationships and vascular impedance. We measured RV contractility by the end-systolic pressure-volume relationship (Ees), PA effective elastance by the end-diastolic to end-systolic relationship (Ea), and RV-PA coupling efficiency by the Ees/Ea ratio. PA constriction persistently increased PA resistance and elastance, increased Ea from 0.95 +/- 0.07 to 3.01 +/- 0.28 mm Hg/mL, decreased Ees from 1.17 +/- 0.09 to 0.58 +/- 0.07 mm Hg/mL, and decreased Ees/Ea from 1.26 +/- 0.09 to 0.22 +/- 0.03 (p < .05). Dobutamine did not affect pulmonary hemodynamics, markedly increased RV contractility, and improved RV-PA coupling. Levosimendan decreased PA resistance and elastance, increased RV contractility, and restored RV-PA coupling. Compared with dobutamine, levosimendan decreased RV afterload and therefore better restored RV-PA coupling at similar inotropic state. A transient increase in PA pressure persistently worsens PA hemodynamics, RV contractility, RV-PA coupling, and cardiac output. Levosimendan restores RV-PA coupling better than dobutamine because of similar inotropic effects and additional pulmonary vasodilatory effects.Critical Care Medicine 12/2006; 34(11):2814-9. · 6.33 Impact Factor -
Article: Albumin administration improves organ function in critically ill hypoalbuminemic patients: A prospective, randomized, controlled, pilot study.
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ABSTRACT: To test the hypothesis that administration of albumin to correct hypoalbuminemia might have beneficial effects on organ function in a mixed population of critically ill patients. : Prospective, controlled, randomized study. Thirty-one-bed, mixed medicosurgical department of intensive care. All adult patients with a serum albumin concentration < or =30 g/L were assessed for eligibility. Principal exclusion criteria were expected length of stay <72 hrs, life expectancy <3 months or a do-not-resuscitate order, albumin administration in the preceding 24 hrs, or evidence of fluid overload. The 100 patients were randomized to receive 300 mL of 20% albumin solution on the first day, then 200 mL/day provided their serum albumin concentration was <31 g/dL (albumin group), or to receive no albumin (control group). The primary outcome was the effect of albumin administration on organ function as assessed by a delta Sequential Organ Failure Assessment score from day 1 to day 7 (or the day of intensive care discharge or death, whichever came first). The two groups of 50 patients were comparable at baseline for age, gender, albumin concentration, and Acute Physiology and Chronic Health Evaluation II score. Albumin concentration did not change over time in the control group but increased consistently in the albumin group (p < .001). Organ function improved more in the albumin than in the control group (p = .026), mainly due to a difference in respiratory, cardiovascular, and central nervous system components of the Sequential Organ Failure Assessment score. Diuretic use was identical in both groups, but mean fluid gain was almost three times higher in the control group (1679 +/- 1156 vs. 658 +/- 1101 mL, p = .04). Median daily calorie intake was higher in the albumin than in the control group (1122 [935-1158] vs. 760 [571-1077] kcal, p = .05). Albumin administration may improve organ function in hypoalbuminemic critically ill patients. It results in a less positive fluid balance and a better tolerance to enteral feeding.Critical Care Medicine 10/2006; 34(10):2536-40. · 6.33 Impact Factor -
Article: Effects of ramipril on renal function during progressive overpacing-induced heart failure in dogs.
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ABSTRACT: To investigate the effects of preventive angiotensin converting enzyme inhibitor treatment with ramipril in dogs with progressively severe experimentally induced heart failure. 20 dogs. Dogs were randomly allocated to receive no treatment (control) or ramipril (0.125 mg/kg, PO, daily) for 7 weeks. Physical examination, repetitive catheterization of the right side of the heart, and echocardiography were performed before the study (day 0) and weekly for 7 weeks. Renal plasma flow (RPF) as determined by para-aminohippuric acid clearance and glomerular filtration rate (GFR) as determined by creatinine and iohexol clearances were measured on day 0 and at weeks 4 and 7. Overpacing induced a progressive increase in right atrial pressure (RAP) and pulmonary artery pressure, occluded (PAPO), with a decrease in systemic arterial pressure. There were progressive alterations of echocardiographic indices of diastolic and systolic ventricular function. The RPF and GFR decreased before cardiac output decreased, and filtration fraction increased. The logarithm of the urinary sodium-to-potassium concentration ratio (log(10)[Na(+)/K(+)]) decreased. Significant effects of ramipril included a delay in clinical signs of heart failure, a late decrease in RAP and PAPO, and increases in the sodium excretion fraction and log(10)(Na(+)/K(+)). There was a satisfactory agreement between the creatinine and iohexol clearance measurements. Results suggest that, in this rapid-evolving, dilated cardiomyopathy, activation of the renin-angiotensin system contributes to the pathophysiology of heart failure late in the disease and essentially by an activation of renal salt and water retention.American Journal of Veterinary Research 08/2006; 67(7):1236-43. · 1.27 Impact Factor -
Article: Left and right ventriculo-arterial coupling in a patient with congenitally corrected transposition.
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ABSTRACT: The single beat method was used to evaluate right and left ventriculo-arterial coupling in an asymptomatic patient with congenitally corrected transposition. The ratio of ventricular end-systolic to arterial elastances was normal for the left ventricle coupled to the pulmonary circulation, and depressed for the right ventricle coupled to the systemic circulation. This result suggests that chronic uncoupling of the right ventricle to the systemic circulation might play a role in the pathophysiology produced by congenitally corrected transposition.Cardiology in the Young 01/2006; 15(6):647-9. · 0.76 Impact Factor -
Article: Prevention of pulmonary vascular remodeling and of decreased BMPR-2 expression by losartan therapy in shunt-induced pulmonary hypertension.
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ABSTRACT: The renin-ANG system has been reported to be overexpressed in pulmonary arterial hypertension (PAH). We investigated the effects of ANG receptor-1 blockade by losartan on hemodynamics and signaling molecules in a piglet overflow model of early PAH. Twenty-six 3-wk-old piglets were randomized to placebo or losartan therapy (1 mg.kg(-1).day(-1)) after anastomosis of the inominate to the main pulmonary artery or after a sham operation. Three months later, the animals underwent a hemodynamic evaluation, followed by pulmonary tissue sampling for morphometry, immunohistochemistry, and real-time quantitative-PCR. Chronic systemic-to-pulmonary shunting increased the pulmonary vascular resistance from 2.5 +/- 0.2 to 6.2 +/- 0.3 mmHg.l(-1).min.m(-2) and arteriolar medial thickness from 13.6 to 25.4%. These changes were associated with increased expressions of ANG II and its type 1 (AT1) and type 2 (AT2) receptors, endothelin-1 (ET-1) and its type B receptor (ETB), and angiopoietin-1, together with decreased expressions of bone morphogeneic protein receptor-1A and -2 (BMPR-1A and BMPR-2, respectively) and unchanged expression of the receptor tyrosine kinase with immunoglobulin and EGF homology domains-2 (Tie 2). Pretreatment with losartan decreased shunt-induced pulmonary vascular resistance and medial thickness by 51% and 35%, respectively. Losartan therapy was associated with persistent overexpressions of ANG II, AT2, ET-1, ETB, and angiopoietin-1 and with a return to normal of the BMPR-2 expression. These results suggest that ANG II contributes to left-to-right, shunt-induced PAH.AJP Heart and Circulatory Physiology 01/2006; 289(6):H2319-24. · 3.71 Impact Factor
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Institutions
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2003–2013
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Université Libre de Bruxelles
- • Faculté de Médecine
- • Department of Intensive Care Unit
Brussels, BRU, Belgium
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2011
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Assistance Publique Hôpitaux de Marseille
- Service d'anesthésie réanimation 1
Marseille, Provence-Alpes-Cote d'Azur, France
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2003–2010
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Vrije Universiteit Brussel
Brussels, BRU, Belgium
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2009
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University Hospital Brussels
Brussels, BRU, Belgium
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2006
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University-Hospital Brugmann UVC
Brussels, BRU, Belgium
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2002
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Washington University in St. Louis
Saint Louis, MO, USA
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