Mechanisms of regional ischemia and antianginal drug action during exercise.
Several mechanisms involved in the production of regional exercise-induced ischemia are described. Each offers the potential for modification using different types of antianginal drugs operating to alter regional O2 demands, improve regional perfusion, or both, leading to reduced ischemia and increased contractile function in the ischemic zone. Evidence is presented for matching of regional subendocardial myocardial blood flow and flow per beat with regional myocardial contraction at various levels of ischemia at rest, during steady-state exercise, and after antianginal drugs, signifying a particularly important role for heart rate control. In addition to reducing myocardial O2 demand per minute, beta-blockers and bradycardic drugs cause improvement of absolute subendocardial blood flow and particularly flow per beat by producing vasoconstriction in the epicardial region of the ischemic zone, with improvement of transmural blood flow distribution. Vasodilator drugs can act at several locations to increase regional blood flow and also to decrease O2 demands. A recruitable vasodilator reserve has been shown to exist during exercise-induced ischemia either in native resistance vessels, collateral channels, or both, which appears to be due at least in part to reduction of increased alpha-adrenergic constrictor tone to the coronary vessels during exercise, even in the presence of severe ischemia. The potential for additive effects using combinations of bradycardic and vasodilating agents are described within a framework relating regional subendocardial blood flow to regional systolic contraction. The experimental findings described suggest some potential new directions for antianginal therapy and, along with recent clinical observations, support the use of combinations of antianginal agents that act by different mechanisms.
Ross
J
J
Department of Medicine, University of California San Diego School of Medicine, La Jolla 92093.
D000787:Angina Pectoris / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D004285:Dogs; D015444:Exercise; D006801:Humans; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents