title: Effects of epoprostenol and sildenafil on right ventricular function in hypoxic volunteers: a tissue Doppler imaging study.
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.
authors.affiliation: Department of Pathophysiology, Faculty of Medicine of the Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Adriana
authors.initials: A
authors.lastname: Pavelescu
authors.forename: Robert
authors.initials: R
authors.lastname: Naeije
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001530:Belgium; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015150:Echocardiography, Doppler; D011464:Epoprostenol / Q000627:therapeutic use*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D000860:Hypoxia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D016018:Least-Squares Analysis; D016014:Linear Models; D008297:Male; D010879:Piperazines / Q000627:therapeutic use*; D010919:Placebos; D011237:Predictive Value of Tests; D011651:Pulmonary Artery / Q000187:drug effects* / Q000503:physiopathology; D011687:Purines / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000627:therapeutic use*; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects; D016278:Ventricular Function, Right / Q000187:drug effects*; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D010879:Piperazines; D010919:Placebos; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D011464:Epoprostenol