Abstract 16790: Positive Inotropic Effects of Acute Intravenous Iloprost in Rats with Chronic Pulmonary Arterial Hypertension
Introduction: Pulmonary arterial hypertension (PAH) is a syndrome of increased pulmonary vascular resistance that ultimately leads to right ventricular failure. Supportive management for decompensated RV function in chronic PAH is not very well understood and acute administration of prostacyclins is sometimes considered. While prior studies of inotropic effects of prostacyclins on models of acute pulmonary hypertension have yielded mixed results, evaluation of these effects under conditions of chronic PAH and RV dysfunction have not been reported using invasive hemodynamics. We sought to study the effects of an acute intravenous infusion of iloprost on right ventricular contractility in a rat model of chronic PAH.
Methods: Ten Sprague-Dawley rats weighing 250-350g were treated with monocrotaline 60mg/kg IP. Six weeks later, baseline hemodynamic assessment was done using pressure-volume measurements using conductance catheterization, and these were repeated 10-15 minutes after IV infusion of iloprost (20µg/kg). RV contractility was assessed by the End-systolic pressure volume relationship (ESPVR), and Ees/Ea (RV/PA coupling) were obtained by transient decrease in preload (IVC occlusion). All values are reported as mean ± SEM. Paired and unpaired analysis was performed using Student's t-test.
Results: Animals had evidence of PAH and RV hypertrophy. RV/LV+septum weight was 0.40 (±0.03). Right ventricular systolic pressure (RVSP) was 39.83 (±1.62) mmHg. Administration of iloprost demonstrated a significant increase in the slope of the ESPVR from 0.29 (±0.02) to 0.42 (±0.05) (p<0.05), and ventricular-arterial coupling index Ees/Ea increased from 0.63 (±0.07) to 0.82 (±0.06) (p<0.05). RV contractility index (max dP/dt normalized for instantaneous pressure) increased from 94.11/s to 114.5/s (p<0.05) as did RV ejection fraction from 48.0% to 52.5% (p<0.05). Pulmonary vascular resistance decreased from 0. 50 (±0.05) to 0.33 (±0.05) Wood units (p<0.05).
Conclusion: Our present study suggests a positive inotropic effect of iloprost (as evidenced by RV contractility index and ESPVR on remodeled right ventricles resulting from chronic PAH. The role of prostacyclins in the acute treatment algorithm of PAH merits further study.
- © 2011 by American Heart Association, Inc.