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

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Abstract
The effect of a new inotropic agent, OPC-8212 (2(1H)-quinolinone derivative), on myocardial oxygen consumption (MV^^·O2) 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-μm microspheres and volume loading. OPC-8212 significantly increased LV mad 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 MV^^·O2 in the normal hearts and even decreased MV^^·O2 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 MV^^·O2 by positive inotropic effect is offset by a decrease in MV^^·O2 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.