Effects of inhaled iloprost on right ventriculovascular coupling and ventricular interdependence in acute pulmonary hypertension

Introduction

Prostacyclin inhalation is increasingly used to treat acute pulmonary hypertension (PHT) and right ventricular (RV) failure. Prostacyclins not only affect vasomotor tone, but may also have cyclic adenosine 3',5'-monophosphate-mediated positive inotropic effects and modulate autonomic nervous system (ANS) tone. We studied the role of these different mechanisms in the overall hemodynamic effects produced by iloprost (ILO) inhalation in an experimental model of acute PHT.

Methods

Twenty-six pigs were instrumented with biventricular conductance catheters, a pulmonary artery (PA) flow probe and a high-fidelity PA-pressure catheter. The effects of 50 μg inhaled ILO were studied in healthy animals with and without blockade of the ANS, and in animals with acute hypoxia-induced PHT.

Results

ILO had minimal hemodynamic effects in healthy animals and produced no direct effects on myocardial contractility after pharmacological ANS blockade. During PHT, ILO resulted in a 51% increase in cardiac output when compared with placebo (5.6 ± 0.7 vs 3.7 ± 0.8 l/min, P = 0.0013), a selective reduction of RV afterload (effective PA-elastance (PA-Ea): from 0.6 ± 0.3 vs 1.2 ± 0.5 mmHg/ml; P = 0.0005) and a significant increase in left ventricular (LV) end-diastolic volume (91 ± 12 vs 70 ± 20 ml, P = 0.006). Interestingly, RV contractility was reduced after ILO (slope of preload recruitable stroke work: 3.4 ± 0.8 vs 2.2 ± 0.5 mW/ml; P = 0.0002), while ventriculovascular coupling remained essentially preserved (ratio of RV end-systolic elastance over PA-Ea: 0.97 ± 0.33 vs 1.03 ± 0.15).

Conclusion

In acute PHT, ILO improved global hemodynamics primarily via selective pulmonary vasodilation and a restoration of LV preload. The reduction of RV afterload was associated with a paradoxical decrease in RV contractility. This appears to reflect an indirect mechanism serving to maintain ventriculovascular coupling at the lowest possible energetic cost, since no evidence for a direct negative inotropic effect of ILO was found.