Effect of Coronary Perfusion on Myocardial Contractility in the Heart

Abstract

Coronary perfusion pressure and blood flow are closely linked to myocardial metabolic states and contractility. When coronary perfusion pressure is decreased below the level of the coronary flow autoregulation, myocardial contractility is markedly decreased: myocardial ischemia causes accumulation of H+ and inorganic phosphates, both of which decrease the myofilament sensitivity to Ca2+ and maximal response of myofilaments to Ca2+. Furthermore, adenosine and endothelial-dependent relaxant factor (EDRF; NO), produced during ischemia, stimulate Gi proteins and guanylate cyclase, respectively, both of which have been reported to decrease myocardial contractility. In turn, norepinephrine is released according to the severity of myocardial ischemia, which tends to compensate the depression of myocardial contractility. On the other hand, even if myocardial ischemia is not apparent due to coronary flow autoregulation during mild reduction of coronary perfusion pressure, myocardial contractility is decreased, recognized as Gregg’s phenomenon. There are several hypotheses to explain this phenomenon: (1) decreases in sarcomere length of the myofilaments; (2) reversal of latent myocardial ischemia; (3) release of cardiodepressive agents; and (4) decreases in Ca2+ transient and Ca2+ sensitivity. We measured Ca2+ transients in the ferret Langendorff preparation at various perfusion pressures. The amplitude of Ca2+ transients was decreased when coronary perfusion pressure was reduced within the range of coronary flow autoregulation. Considering these results together, we support the tight linkage between coronary perfusion and myocardial contractility in normal and ischemic hearts. The concerted interaction between myocardial perfusion and intracellular Ca2+ contraction may be essential for maintaining homeostasis of myocardial cellular function.