Hypoxia has been reported to alter left ventricular (LV) diastolic function, but associated changes in right ventricular (RV) systolic and diastolic function remain incompletely documented. We used echocardiography and tissue Doppler imaging to investigate the effects on RV and LV function of 90 min of hypoxic breathing (fraction of inspired O 2 of 0.12) compared with those of dobutamine to reproduce the same heart rate effects without change in pulmonary vascular tone in 25 healthy volunteers. Hypoxia and dobutamine increased cardiac output and tricuspid regurgitation velocity. Hypoxia and dobutamine increased LV ejection fraction, isovolumic contraction wave velocity (ICV), acceleration (ICA), and systolic ejection wave velocity (S) at the mitral annulus, indicating increased LV systolic function. Dobutamine had similar effects on RV indexes of systolic function. Hypoxia did not change RV area shortening fraction, tricuspid annular plane systolic excursion, ICV, ICA, and S at the tricuspid annulus. Regional longitudinal wall motion analysis revealed that S, systolic strain, and strain rate were not affected by hypoxia and increased by dobutamine on the RV free wall and interventricular septum but increased by both dobutamine and hypoxia on the LV lateral wall. Hypoxia increased the isovolumic relaxation time related to RR interval (IRT/RR) at both annuli, delayed the onset of the E wave at the tricuspid annulus, and decreased the mitral and tricuspid inflow and annuli E/A ratio. We conclude that hypoxia in normal subjects is associated with altered diastolic function of both ventricles, improved LV systolic function, and preserved RV systolic function. dobutamine; right ventricle; left ventricle; echocardiography EXPOSURE TO HYPOXIA in humans is associated with a preserved cardiac output at rest but limited cardiac output during exercise (26). The mechanisms accounting for this limitation of maximal cardiac output remain unclear. Echocardiographic studies in hypoxic healthy volunteers have shown a preservation of left ventricular (LV) contractility but reported altered mitral flow patterns, suggestive of LV diastolic dysfunction (2,6,19). Hypoxic pulmonary vasoconstriction would be expected to induce major right ventricle (RV) function changes in response to increased afterload (21). It has been recently suggested that inhibition of the hypoxic pressor response by sildenafil improves exercise capacity at high altitude by allowing for increased cardiac output and O 2 delivery to the tissues (10).How hypoxia and hypoxic pulmonary vasoconstriction-related increase in afterload affect RV function is not exactly known.Standard Doppler echocardiography to evaluate RV function is limited by its complex geometry and nonconcentric contraction patterns (3, 4, 16). We wondered whether tissue Doppler imaging (TDI) could provide a more exact assessment of RV function. This recently introduced approach allows the noninvasive determination of myocardial velocity in the human heart and has the potential of shape-independent a...

Altitude exposure is associated with decreased exercise capacity and increased pulmonary vascular resistance (PVR).Echocardiographic measurements of pulmonary haemodynamics and a cardiopulmonary exercise test were performed in 13 healthy subjects at sea level, in normoxia and during acute hypoxic breathing (1 h, 12% oxygen in nitrogen), and in 22 healthy subjects after acclimatisation to an altitude of 5,050 m. The measurements were obtained after randomisation, double-blinded to the intake of placebo or the endothelin A receptor blocker sitaxsentan (100 mg?day -1 for 7 days). Blood and urine were sampled for renal function measurements. Normobaric as well as hypobaric hypoxia increased PVR and decreased maximum workload and oxygen uptake (V9O 2 ,max). Sitaxsentan decreased PVR in acute and chronic hypoxia (both p,0.001), and partly restored V9O 2 ,max, by 30 % in acute hypoxia (p,0.001) and 10% in chronic hypoxia (p,0.05). Sitaxsentan-induced changes in PVR and V9O 2 ,max were correlated (p50.01). Hypoxia decreased glomerular filtration rate and free water clearance, and increased fractional sodium excretion. These indices of renal function were unaffected by sitaxsentan intake.Selective endothelin A receptor blockade with sitaxsentan improves mild pulmonary hypertension and restores exercise capacity without adverse effects on renal function in hypoxic normal subjects.

The phosphodiesterase-5 inhibitor sildenafil has been reported to improve hypoxic exercise capacity, but the mechanisms accounting for this observation remain incompletely understood. Sixteen healthy subjects were included in a randomized, double-blind, placebo-controlled, cross-over study on the effects of 50-mg sildenafil on echocardiographic indexes of the pulmonary circulation and on cardiopulmonary cycle exercise in normoxia, in acute normobaric hypoxia (fraction of inspired O2, 0.1), and then again after 2 weeks of acclimatization at 5000 m on Mount Chimborazo (Ecuador). In normoxia, sildenafil had no effect on maximum VO2 or O2 saturation. In acute hypoxia, sildenafil increased maximum VO2 from 27 +/- 5 to 32 +/- 6 mL/min/kg and O2 saturation from 62% +/- 6% to 68% +/- 9%. In chronic hypoxia, sildenafil did not affect maximum VO2 or O2 saturation. Resting mean pulmonary artery pressure increased from 16 +/- 3 mmHg in normoxia to 28 +/- 5 mmHg in normobaric hypoxia and 32 +/- 6 mmHg in hypobaric hypoxia. Sildenafil decreased pulmonary vascular resistance by 30% to 50% in these different conditions. We conclude that sildenafil increases exercise capacity in acute normobaric hypoxia and that this is explained by improved arterial oxygenation, rather than by a decrease in right ventricular afterload.

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Background-This large, prospective, multicentric study was performed to analyze the distribution of tricuspid regurgitation velocity (TRV) values during exercise and hypoxia in relatives of patients with idiopathic and familial pulmonary arterial hypertension (PAH) and in healthy control subjects. We tested the hypothesis that relatives of idiopathic/familial PAH patients display an enhanced frequency of hypertensive TRV response to stress and that this response is associated with mutations in the bone morphogenetic protein receptor II (BMPR2) gene. Methods and Results-TRV was estimated by Doppler echocardiography during supine bicycle exercise in normoxia and during 120 minutes of normobaric hypoxia (FIO 2 ϭ12%; Ϸ4500 m) in 291 relatives of 109 PAH patients and in 191 age-matched control subjects. Mean maximal TRVs were significantly higher in PAH relatives during both exercise and hypoxia. During exercise, 10% of control subjects but 31.6% of relatives (PϽ0.0001) exceeded the 90% quantile of mean maximal TRV seen in control subjects. Hypoxia revealed hypertensive TRV in 26% of relatives (Pϭ0.0029). Among control subjects, TRV at rest was not related to age, sex, body mass index, systemic blood pressure, smoking status, or heart rate. Within kindreds identified as harboring deleterious mutations of the BMPR2 gene, a hypertensive TRV response occurred significantly more often compared with those without detected mutations. Conclusions-Pulmonary hypertensive response to exercise and hypoxia in idiopathic/familial PAH relatives appears as a genetic trait with familial clustering, being correlated to but not caused by a BMPR2 mutation. The suitability of this trait to predict manifest PAH development should be addressed in long-term follow-up studies.