Acute effects of a novel inotropic agent, OPC-18790 (toborinone), on hemodynamics and myocardial energetics in patients with chronic heart failure

We examined the acute effects and safety of OPC-18790 (toborinone), a novel water-soluble quinolinone derivative, on mechanoenergetics in 12 patients with chronic congestive heart failure. OPC-18790 was intravenously administered at a rate of 5 μg/kg/min or 10 μg/kg/min. Left ventricular (LV) pressure-volume data were obtained by conductance methods and myocardial oxygen consumption (MVO₂) was measured using a Webster catheter. Heart rate was slightly increased in all patients after receiving OPC-18790. Ventricular preload as assessed by LV end-diastolic volume index significantly declined, and mean and systolic pulmonary artery pressure also fell after OPC-18790 infusion. In addition to venodilation, systemic vasodilation was observed after OPC-18790 infusion. Systolic and mean arterial pressure, and systemic vascular resistance significantly declined after OPC-18790 infusion. Effective arterial elastance (Ea), which represents both the mean vascular resistance and the pulsatile components, fell significantly. LV contractility as assessed by end-systolic elastance (Ees) significantly rose after OPC- 18790 infusion. Cardiac index and ejection fraction improved significantly. External work (EW) was unchanged. The isovolumic relaxation time constant was prolonged before OPC-18790 infusion and OPC-18790 shortened this time constant rate. MVO₂ was reduced after OPC-18790 infusion probably due to a reduction of wall tension. Ventricular-arterial coupling (Ea/Ees) was far less than optimal before OPC-18790 infusion and was near optimal after OPC 18790 infusion. Mechanical efficiency (EW/MVO₂) was improved along with the Ea/Ees ratio. Systolic arterial pressure fell by 40 or 50 mmHg after OPC- 18790 infusion in 2 patients probably due to vasodilation. In conclusion, OPC-18790 had favorable mechanoenergetic effects in patients with congestive heart failure. Despite enhancing contractility, OPC-18790 reduced MVO₂ and improved mechanical efficiency probably due to its favorable effects on loading conditions. These findings suggest that OPC-18790 may be useful for short-term treatment of patients with congestive heart failure.