Beneficial effect of OPC-8212 (3,4-dihydro-6-(4-(3,4-dimethoxy benzoyl)-1-piperazinyl)-2(1H)-quinolinone on myocardial oxygen consumption in dogs with ischemic heart failure.

The effect of a new inotropic agent, OPC-8212 (2(1H)-quinolinone derivative), on myocardial oxygen consumption (MVO2) following intravenous administration (1 and 3 mg/kg/min) was studied in normal and ischemic failing hearts in open chest dogs. Ischemic failing heart was obtained by intracoronary injection of 15-micron microspheres and volume loading. OPC-8212 significantly increased LV max dP/dt and decreased mean aortic pressure, whereas heart rate was not altered in both normal and failing hearts. Despite the remarkable positive inotropic effect, this agent did not increase MVO2 in the normal hearts and even decreased MCO2 in the ischemic failing hearts associated with a decrease in LV end-diastolic pressure and hence, LV chamber size. These results indicate that OPC-8212 does not increase myocardial oxygen demand, probably because the increase in MVO2 by positive inotropic effect is offset by a decrease in MVO2 due to a decrease in chamber size. Thus, OPC-8212 may be promising for the treatment of congestive heart failure with reduced coronary flow reserve.