Cardiovascular pharmacology of quazodine (MJ‐1988), with particular reference to effects on myocardial blood flow and metabolic heat production

Abstract

Summary1. The effects of intravenous infusions of quazodine (6,7-dimethoxy-4-ethylquinazoline; MJ-1988) on myocardial blood flow, myocardial metabolic heat production and on general haemodynamics have been studied in cats anaesthetized with sodium pentobarbitone. 2. Quazodine (0-25 and 05 (mg/kg)/min for 10 min) decreased diastolic blood pressure, peripheral vascular resistance, systolic ejection time and left ventricular end-diastolic pressure. Heart rate, cardiac effort, output and external work and left ventricular dP/dt were markedly increased. These changes are indicative of increased myocardial contractility and peripheral vasodilatation.3. In a dose of (1-0 mg/kg)/min, quazodine had a more marked hypotensive effect, systolic pressure being significantly reduced, and had less effect on left ventricular dP/dt and cardiac effort. Calculated external cardiac work was slightly reduced and there were very occasional nodal arrhythmias. 4. Changes in heart rate, aortic dP/dt and diastolic blood pressure induced by quazodine were unaffected by the previous administration of the 3-adrenoceptor blocking agent alprenolol in a dose (1-0 mg/kg) which abolished the effects of isoprenaline. 5. In all doses, quazodine markedly increased local blood flow (by 70-540%) around an implanted myocardial heated thermocouple recorder. 'Corrected temperature', an index of local myocardial metabolic heat production, was almost unchanged and it is suggested that increased myocardial contractility, occurring with unchanged metabolic heat production and oxygen consumption, probably results from a concomitant decrease in intramural wall tension.

The Haemodynamic Effects of Quazodine, a Cardiac Stimulant, in Experimental E. Coli Endotoxin Shock in the Cat

“…The cardiovascular effects produced by quazodine before the administration of endotoxin were similar to those previously described in similar experiments (Parratt & Winslow, 1971a. Tracings from one experiment are illustrated in Fig.…”

“…and one way to test this hypothesis would be to give a cardiac stimulant drug which acts distal to 1 he B-adrenoreceptor. Quazodine is such a drug; its cardiac stimulant effects are unaltered by B-adrenoreceptor blocking agents (Parratt & Winslow, 1971a). Quazodine increases the iintracellular concentration of cyclic AMP by inhibiting phosphodiesterase (Amer & Browder, 1971 ;Parratt & Winslow, 1971b): in the myocardium, this would be expected to increase contractility.…”

“…External cardiac work, stroke volume, myocardial vascular resistance, and peripheral vascular resistance were calculated as previously described (Parratt & Winslow, 1971a.…”