Coronary Perfusion as the Major Determinant of Myocardial Contractility in the Heart: Implication for Myocardial Hibernation

Abstract

Coronary perfusion pressure and blood flow are closely linked to myocardial metabolic states and contractility. When coronary perfusion pressure decreases 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 EDRF (NO), produced during ischemia, stimulate adenylate and guanulate 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, when myocardial ischemia is not apparent due to coronary flow autoregulation during mild reduction of coronary perfusion pressure, myocardial contractility decreases, 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 either Ca²⁺ transient or Ca²⁺ sensitivity. Ca²⁺ transients were measured in the ferret Langendorff preparation at various perfusion pressure; the amplitude of Ca²⁺ transients was decreased when coronary perfusion pressure was reduced in the range of coronary flow autoregulation. Taken together, these results support the hypothesis of the tight linkage between coronary perfusion and myocardial contractility in normal and ischemic hearts. The concert interaction between myocardial perfusion and intracellular Ca²⁺ concentration may be essential for maintaining homeostasis of myocardial cellular function.