Effects of Nipradilol, a New β-Adrenoceptor Blocking Agent with Vasodilating Properties, on Transmural Energy Metabolism in the Underperfused Canine Heart

Abstract

Abstract-Effects of nipradilol on hemodynamics and transmural energy me tabolism of underperfused (ischemic) canine hearts were investigated. The ischemic heart was prepared by constricting a tube connecting the circumflex coronary artery with the carotid artery for 10 min so that the perfusion pressure (CPP) was reduced to 30 mmHg. The reduction in CPP resulted in decreases in coronary blood flow (CBF) by 70%, regional myocardial contractile force (MCF) by 30%, myocardial ATP contents by 32% (inner layer)-22% (outer) and creatine phosphate by 75% (inner)-60% (outer). Increases in the left ventricular end diastolic pressure (LVEDP) by 4.8 mmHg, myocardial inorganic phosphate con tents by 1.9 times (inner)-1 .3 (outer) and lactate by 4.3 times (inner)-2.4 (outer) were also observed. In dogs with normal hearts, an infusion of nipradilol (10 ,ug/ kg/min, i.v., for 1 5 min) decreased CPP by 25%, CBF by 40%, cardiac effort index by 45% and MCF by 30 to 40%, and it slightly increased LVEDP without affecting myocardial high-energy phosphate and lactate levels. In ischemic hearts, nipradilo! infusion starting 5 min before ischemia attenuated the ischemia-induced elevation of LVEDP to 1.8 mmHg, and the ischemia-induced changes in high energy phosphate contents to 1/2 (inner)-1/3 (outer) and changes in lactate to 1 /6 (inner)-1/10 (outer). These results indicate that nipradilol improves the ischemic derangement of both transmural energy metabolism and hemodynamics.

Effect of Nipradilol on Myocardial Energy Metabolism in the Dog Ischaemic Heart

“…Noguchi & Sakanashi (1 987) reported that nipradilol alleviates acute myocardial ischaemia produced by partial occlusion of the left circumflex in the anaesthetized dog. Higuchi & Asakawa (1987) using an extra-corporeal circuit method, reported that nipradilol improves the ischaemic derangement of both transmural energy metabolism and haemodynamics in dogs, and Haneda et al (1989) observed a protective effect of nipradilol on the ischaemic myocardium in the rat isolated Perfused heart.…”