The effect of Riociguat on cardiovascular function and efficiency in healthy, juvenile pigs.

INTRODUCTION

Riociguat is a soluble guanylate cyclase stimulator approved for the treatment of pulmonary hypertension. Its effect on cardiometabolic efficiency is unknown. A potential cardiac energy sparing effect of this drug could imply a positive prognostic effect, particularly in patients with right heart failure from pulmonary hypertension.

METHOD: We infused Riociguat in six healthy juvenile pigs and measured the integrated cardiovascular effect and myocardial oxygen consumption. To assess the interplay with NO-blockade on cardiac function and efficiency we also administered the NO-blocker L- NAME to the animals after Riociguat.

RESULTS AND DISCUSSION: Infusion of 100 µg/kg Riociguat gave modest systemic vasodilatation seen as a drop in coronary and systemic vascular resistance of 36% and 26%, respectively. Right and left ventriculoarterial coupling index (Ees/Ea), stroke work efficiency (SWeff), and the relationship between left ventricular myocardial oxygen consumption (MVO2 ) and total mechanical work (pressure-volume area; PVA) were unaffected by Riociguat. In contrast, systemic and pulmonary vasoconstriction induced by L-NAME (15 mg/kg) shifted the Ees/Ea ratio toward reduced SWeff in both systemic and pulmonary circulation. However, there was no surplus oxygen consumption, that was measured by the MVO2 /PVA relationship after L-NAME in Riociguat-treated pigs. This suggests that Riociguat can reduce the NO-related cardiometabolic inefficiency previously observed by blocking the NO pathway.