Hirofumi Kanda

A novel inotropic vasodilator, OPC-18790, reduces myocardial oxygen consumption and improves mechanical efficiency with congestive heart failure

We analyzed the left ventricular (LV) pressure-volume relation and obtained direct measurements of myocardial oxygen consumption (MVO2) before and after drug administration in 21 patients with New York Heart Association functional class II to III congestive heart failure to compare the mechanoenergetic effects of OPC-18790, a novel inotropic agent, and dobutamine. Pressure-volume data were obtained by the conductance method, and MVO2 measurements were obtained with a double-thermistor coronary sinus catheter before and after administration of OPC-18790 and dobutamine. The LV end-diastolic volume index decreased significantly without an increase in the heart rate after administration of OPC-18790, unlike that after administration of dobutamine. Both drugs significantly increased the LV contractility index (Emax) and caused similar improvements in ventricular-arterial coupling. OPC-18790 significantly reduced MVo2, whereas dobutamine increased MVo2. The ratio of the pressure-volume area to myocardial oxygen consumption (PVA/MVo2) remained unchanged after administration of OPC-18790 and decreased after administration of dobutamine. The ratio of external work to the pressure-volume area (EW/PVA) was similarly increased by both drugs, resulting in an improvement in mechanical efficiency (EW/MVo2) with OPC-18790 (p < 0.05) and in a deterioration with dobutamine (p < 0.05). OPC-18790 had an energetic advantage over dobutamine in spite of its positive inotropic effect. Our findings suggest that OPC-18790 may be useful for the treatment of patients with congestive heart failure.