Epoprostenol treatment of acute pulmonary hypertension is associated with a paradoxical decrease in right ventricular contractility

OBJECTIVE: Prostacyclins have been suggested to exert positive inotropic effects which would render them particularly suitable for the treatment of right ventricular (RV) dysfunction due to acute pulmonary hypertension (PHT). Data on this subject are controversial, however, and vary with the experimental conditions. We studied the inotropic effects of epoprostenol at clinically recommended doses in an experimental model of acute PHT. DESIGN AND SETTING: Prospective laboratory investigation in a university hospital laboratory. SUBJECTS: Six pigs (36 +/- 7kg). INTERVENTIONS: Pigs were instrumented with biventricular conductance catheters, a pulmonary artery (PA) flow probe, and a high-fidelity pulmonary pressure catheter. Incremental doses of epoprostenol (10, 15, 20, 30, 40ng kg(-1) min(-1)) were administered in undiseased animals and after induction of acute hypoxia-induced PHT. MEASUREMENTS AND RESULTS: In acute PHT epoprostenol markedly reduced RV afterload (slopes of pressure-flow relationship in the PA from 7.0 +/- 0.6 to 4.2 +/- 0.7mmHg minl(-1)). This was associated with a paradoxical and dose-dependent decrease in RV contractility (slope of preload-recruitable stroke-work relationship from 3.0 +/- 0.4 to 1.6 +/- 0.2 mW s ml(-1); slope of endsystolic pressure-volume relationship from 1.5 +/- 0.3 to 0.7 +/- 0.3mmHg ml(-1)). Left ventricular contractility was reduced only at the highest dose. In undiseased animals epoprostenol did not affect vascular tone and produced a mild biventricular decrease in contractility. CONCLUSIONS: Epoprostenol has no positive inotropic effects in vivo. In contrast, epoprostenol-induced pulmonary vasodilation in animals with acute PHT was associated with a paradoxical decrease in RV contractility. This effect is probably caused indirectly by the close coupling of RV contractility to RV afterload. However, data from normal animals suggest that mechanisms unrelated to vasodilation are also involved in the observed negative inotropic response to epoprostenol.status: publishe