The role of heart rate in myocardial ischemia and infarction: implications of myocardial perfusion-contraction matching

Abstract

The pathophysiology of myocardial ischemia traditionally has been attributed to disturbances of oxygen demand, as observed in classic effort-induced angina pectoris, or to a primary disruption of coronary blood supply, as in unstable angina or acute myocardial infarction. Laboratory research eliciting various types of perfusion-contraction matching has challenged such a historical distinction between supply and demand-induced determinants of myocardial ischemia. A growing number of clinical studies analyzing the role of heart rate in the course of coronary heart disease suggest the possibility that a common perfusion-contraction scheme may underlie these diverse clinical manifestations. During experimental myocardial ischemia, produced by a low coronary blood flow, regional perfusion-contraction matching exists in which the energy demands and regional contraction are reduced to match the diminished myocardial substrate supply. Heart rate is a major factor influencing transmural blood flow distribution and regional function, because when coronary vasodilation is maximal there is an inverse relation between the level of heart rate and subendocardial perfusion. Thus, in experimental regional ischemia, increasing heart rate reduces subendocardial flow and contraction, whereas slowing of heart rate causes improvement of contraction associated with increased subendocardial blood flow, accompanied by a decrease in outer wall blood flow. Also, "interventricular steal" of blood from the left ventricle by the right ventricle during ischemia can be reversed by slowing the heart rate in the presence of regional ischemia. Improvement of contraction by heart rate slowing is more than would be expected on the basis of the increase in subendocardial perfusion alone, reflecting a combination of decreased oxygen demand and increased oxygen supply, and separate curves relating blood flow per minute to contractile function are observed at different heart rates. However, when perfusion is normalized for heart rate by expressing subendocardial blood flow in units per beat, a single relation is observed at different heart rates. This observation supports the concept of a close coupling between subendocardial blood flow per beat and regional performance, or perfusion-contraction matching, during various levels of ischemia. Based on these principles, it can be predicted that exercise-induced regional ischemia in the presence of coronary stenosis will be attenuated by several mechanisms when heart rate is slowed using either a beta-blocking agent, or a specific bradycardic drug.(ABSTRACT TRUNCATED AT 400 WORDS)