Effects of toborinone on myocardial oxygen consumption in pacing-induced heart failure dogs

The effects of a novel positive inotropic agent, toborinone ((+/-)-6-[3-(3,4-dimethoxy-benzylamino)-2-hydroxypropoxy]-2(1H)- quinolinone, CAS 128667-95-8, OPC-18790), on myocardial oxygen consumption were examined in pacing-induced heart failure dogs. Ten dogs were ventricularly paced at 260 beats/min for 10 days to induce heart failure. Five of them were controls and the remaining five were given toborinone. Dogs were anesthetized with halothane, and cardiac functions, hemodynamics and myocardial oxygen consumption were measured. The peak of the first derivative of left ventricular pressure (LV dP/dt(max)), cardiac output (GO) and mean blood pressure (mBP) were significantly decreased, and left ventricular end-diastolic pressure (LVEDP), mean right atrial pressure (mPAP), pulmonary capillary wedge pressure (PCWP) and mean pulmonary arterial pressure (mPAP) were also significantly increased after 10 days of rapid ventricular pacing. Toborinone (5 and 10 mu g/kg/min) dose-dependently increased LV dP/dt(max), coronary blood flow (CBF) and CO and decreased LVEDP and systemic vascular resistance (SVR) without increasing myocardial oxygen consumption in the pacing-induced heart failure dogs. These results suggest that toborinone may be useful for the management of chronic and congestive heart failure.