Acute Hemodynamic Effects of a New Positive Inotropic Agent, 3,4-Dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-quinolinone (OPC-8212), in Conscious and Anesthetized Dogs

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Abstract
The acute hemodynamic effects of a new cardiotonic agent, OPC-8212 (a 1H-quinolinone derivative), were studied in six conscious and 11 anesthetized dogs using a pair of ultrasonic crystals to measure the left ventricular segment length and a micromanometer to measure the left ventricular pressure. In six anesthetized dogs subjected to aortic constriction, the ascending aortic flow (AoF) was measured before and after intervention. In the anesthetized state bolus injections of OPC-8212 increased the ejection indices dose dependently. Maximum effects were observed at 1 min, the mean velocity of the circumferential fiber shortening (mean Vcf) being augmented by 6.6% with 0.3 mg, by 39.7% with 1 mg, and by 67.2% with 3 mg. These changes were not accompanied by any significant alteration in heart rate. With aortic constriction, the left ventricular wall shortening was significantly reduced. Depressed pump function was dramatically improved with injection of 3 mg of OPC-8212, the dP/dt was elevated by 98%, the AoF by 46%, and the mean Vcf by 78%. In the conscious state the same doses induced the same type of changes in hemodynamics and dimensions, but the amplitude of the response was significantly less; increase in the mean Vcf was by 36% and that of dP/dt by 52%. Thus, OPC-8212 has a potent inotropic effect. The effect was greater in the anesthetized state, or in dogs with depressed ventricular function, than in the conscious state.