Brimioulle, Serge, Pierre Wauthy, Patricia Ewalenko, Benoît Rondelet, Franç oise Vermeulen, Franç ois Kerbaul, and Robert Naeije. Single-beat estimation of right ventricular end-systolic pressure-volume relationship. Am J Physiol Heart Circ Physiol 284: H1625-H1630, 2003. First published January 16, 2003 10.1152/ajpheart.01023.2002.-Assessement of right ventricular (RV) contractility from endsystolic pressure-volume relationships (ESPVR) is difficult due to problems in measuring RV instantaneous volume and to effects of changes in RV preload or afterload. We therefore investigated in anesthetized dogs whether RV ESPVR and contractility can be determined without measuring RV volume and without changing RV preload or afterload. The maximal RV pressure of isovolumic beats (P max) was predicted from isovolumic portions of RV pressure during ejecting beats and compared with Pmax measured during the first beat after pulmonary artery clamping. In RV pressure-volume loops obtained from RV pressure and integrated pulmonary arterial flow, end-systolic elastance (Ees) was assessed as the slope of Pmax-derived ESPVR, pulmonary artery effective elastance (Ea) as the slope of end-diastolic to end-systolic relation, and coupling efficiency as the Ees-to-Ea ratio (Ees/ Ea). Predicted Pmax correlated with observed Pmax (r ϭ 0.98 Ϯ 0.02). Dobutamine increased Ees from 1.07 to 2.00 mmHg/ml and Ees/Ea from 1.64 to 2.49, and propranolol decreased Ees/Ea from 1.64 to 0.91 (all P Ͻ 0.05). After adrenergic blockade, preload reduction did not affect Ees, whereas hypoxia and arterial constriction markedly increased Ea and somewhat increased Ees due to the Anrep effect. Low preload did not affect Ees/Ea and high afterload decreased Ees/Ea. In conclusion, in the right ventricle 1) Pmax can be calculated from normal beats, 2) Pmax can be used to determine ESPVR without change in load, and 3) Pmax-derived ESPVR can be used to assess ventricular contractility and ventricular-arterial coupling efficiency. contractility; preload; afterload; pulmonary hypertension; hypoxia LEFT VENTRICULAR CONTRACTILITY is commonly defined by the end-systolic pressure-volume relationship (ESPVR) (15,16,24). In the right ventricle (RV), the concept of ESPVR is also valid (8, 20) but it is difficult to apply in practice. The major problem is the difficulty in measuring instantaneous RV volume in vivo. In 1988, Kass (13) summarized the limitations of available methods and mentioned the potential of conductance volumetry. Although not completely validated for measurement of instantaneous volume, conductance has been used repeatedly to generate pressure-volume loops in animals and humans (34). The method remains difficult and time consuming and is therefore predominantly used as a research tool (31). A second problem may be the identification of end systole on triangle-shaped RV pressure-volume curves. Several investigators (9, 20) determined ESPVR from end-ejection pressures and volumes, but end ejection and end systole are known to occur at different times in the ...

Background-The dual endothelin-receptor antagonist bosentan has been reported to improve pulmonary arterial hypertension, but the role of endothelins in the pathogenesis of the condition remains uncertain. We investigated the roles of endothelin-1 (ET-1), nitric oxide (NO), vascular endothelial growth factor (VEGF), and tenascin in overcirculation-induced pulmonary hypertension in piglets, as a model of early pulmonary arterial hypertension, with or without bosentan therapy. Methods and Results-Thirty 3-week-old piglets were randomized to placebo or to bosentan 15 mg/kg BID after the anastomosis of the left subclavian artery to the pulmonary arterial trunk or after a sham operation. Three months later, the animals underwent a hemodynamic evaluation followed by cardiac and pulmonary tissue sampling for morphometry, immunohistochemistry, and real-time quantitative PCR. Chronic systemic-to-pulmonary shunting increased circulating plasma ET-1, pulmonary mRNA for ET-1, ET B receptor, inducible NO synthase, VEGF, and pulmonary ET-1 and VEGF proteins. There were increases in myocardial mRNA for ET A receptor and VEGF and in myocardial VEGF protein. Pulmonary and myocardial tissue mRNA for tenascin did not change. Normalized-flow pulmonary artery pressure increased from 20 (2) to 33 (1) mm Hg [mean (SEM)], arteriolar medial thickness increased on average by 83%, and these changes were completely prevented by bosentan therapy. Right ventricular end-systolic elastance increased in proportion to pulmonary arterial elastance with or without bosentan. Conclusions-Experimental overcirculation-induced pulmonary arterial hypertension appears to be causally related to an activation of the pulmonary ET-1 system and as such is completely prevented by the dual endothelin receptor antagonist bosentan. (Circulation. 2003;107:1329-1335.)

Wauthy, Pierre, Alberto Pagnamenta, Fabio Vassalli, Robert Naeije, and Serge Brimioulle. Right ventricular adaptation to pulmonary hypertension: an interspecies comparison. Am J Physiol Heart Circ Physiol 286: H1441-H1447, 2004. First published December 18, 2003 10.1152/ajpheart.00640.2003 adaptation is an important prognostic factor in acute and chronic pulmonary hypertension. Pulmonary vascular basal tone and hypoxic reactivity are known to vary widely between species. We investigated how RV adaptation to acute pulmonary hypertension is preserved in species with low, intermediate, and high pulmonary vascular resistance and reactivity. Acute pulmonary hypertension was induced by hypoxia, distal embolism, and proximal constriction in anesthetized dogs (n ϭ 10), goats (n ϭ 8), and pigs (n ϭ 8). Pulmonary vessels were assessed by flow-pressure curves and by impedance to quantify distal resistance, proximal elastance, and wave reflections. RV function was assessed by pressure-volume curves to quantify afterload, contractility, and ventricular-arterial coupling efficiency. First, hypoxia was associated with a progressive increase of resistance, elastance, and wave reflection from dogs to goats and from goats to pigs. RV contractility increased proportionally to RV afterload, and optimal coupling was preserved in all species. Second, embolism increased resistance and wave reflection but not elastance. The increase in RV contractility matched the increase in RV afterload and optimal coupling was preserved. Finally, proximal pulmonary artery constriction increased resistance, increased and accelerated wave reflection, and markedly increased elastance. RV contractility increased markedly and coupling showed a nonsignificant trend to decrease. We conclude that optimal or near-optimal ventricular-arterial coupling is maintained in acute pulmonary hypertension, whether in absence or presence of chronic species-induced pulmonary hypertension. heart failure; contractility; ventricular-arterial coupling IN CLINICAL PRACTICE, the diagnosis of pulmonary arterial hypertension relies on measurements of pulmonary vascular pressures and cardiac output and calculations of pulmonary vascular resistance (31). These hemodynamic measurements are of prognostic value, with survival being related to cardiac output rather than to pulmonary artery pressure (P PA ) (8,24,33). The clinical state of patients with pulmonary arterial hypertension also appears to be more related to cardiac output than to P PA (25,34). Clinical signs of right heart failure often are not clearly related to progression of pulmonary hypertension as assessed by pulmonary arterial pressure and resistance (34). These observations may be explained by the fact that heart failure in pulmonary hypertension is the consequence of uncoupling of the right ventricle (RV) to the hypertensive pulmonary circulation, which is not actually measured by routine hemodynamic evaluations (30, 34).Sagawa and co-workers (17, 32) previously developed a concept of ventriculoarterial coupling ...

BackgroundCardiac surgery in Jehovah’s Witnesses may be challenging during the operation and postoperative period given their refusal of blood products. The aim of this study was to document our center’s experience with Jehovah’s Witnesses undergoing major cardiac surgery and to compare surgical outcomes with a matched control group.MethodsWe retrospectively reviewed the demographic, perioperative, and in-hospital postoperative data for 31 Jehovah’s Witness patients undergoing surgery from 1991 to 2012 and compared findings with a control group of 62 patients of the same sex and age, who underwent the same type of operations in the same period. Early mortality, major in-hospital morbidity, laboratory findings, and hospital stays were compared between groups.ResultsDemographic data were similar between groups, except that more patients in the Jehovah’s Witness group had extracardiac arteriopathy compared with controls (p = 0.04). There was no difference in predicted mortality, calculated by the Euroscore II, between groups (2.8 ± 3.3 in study group versus 2.4 ± 2.2 in control group, p = 0.469). For postoperative outcomes, there were no differences between Jehovah’s Witnesses versus controls in hospital mortality (3 % versus 2 %, p = 0.548), total drain loss (847 ± 583 mL versus 812 ± 365 mL, p = 0.721), mechanical ventilation time (1.26 ± 2.24 versus 0.89 ± 0.55 days, p = 0.218), intensive care unit stay (4.3 ± 3.9 versus 3 ± 1.4 days, p = 0.080), and hospital stay (12.9 ± 7.6 versus 10.9 ± 6.6 days, p = 0.223).ConclusionsOutcomes after cardiac surgery are similar between Jehovah’s Witnesses and general population, in centers applying rigorous blood patient management protocols.

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A growing aortopulmonary shunt in the young pig is a reliable model of chronic pulmonary hypertension, with medial hypertrophy, increased resistance, and increased elastance. In this model inhaled nitric oxide is a better pulmonary vasodilator than intravenous prostacyclin, with neither drug having a specific inotropic effect, and normal coupling is preserved in chronic and acute pulmonary hypertension.

Pulmonary hypertension occurs commonly in the acute respiratory distress syndrome (ARDS), but associated right ventricular failure is relatively rare. We tested the hypothesis that this apparent contradiction is explained by a peripheral location of the increased pulmonary vascular resistance (Rpva). Experimental ARDS was induced in eight dogs by injection of oleic acid (0.07 ml/kg). Changes in Rpva were evaluated by measurements of pulmonary artery pressure (Ppa) at several levels of flow (Q), which was altered by manipulation of venous return. The analysis of Ppa decay curves after arterial balloon occlusion was used to partition Rpva into arterial and venous segments. Right ventricular afterload was evaluated by determination of pulmonary vascular impedance (Zpva), which was calculated from spectral analysis of Ppa and Q waves. Oleic acid lung injury was associated with an increase in both the slope and the extrapolated pressure intercept of Ppa/Q plots, no change in the partitioning of Rpva, no change in time-domain indices in wave reflection or in pulmonary arterial compliance, and a decrease in both the characteristic impedance and pulsatile component of total right ventricular hydraulic load. We conclude that the site of increased Rpva in oleic acid lung injury is the smallest pulmonary arterioles, which, together with a decreased characteristic impedance, contributes to minimize right ventricular afterload.

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