Calcium antagonists and the stunned myocardium.
"Stunned myocardium" is defined as the prolonged but transient contractile dysfunction of viable myocardium salvaged by reperfusion. For example, a brief 15-min episode of coronary artery occlusion does not result in myocyte necrosis, yet contractile function of the previously ischemic tissue remains profoundly depressed at 0-30% of baseline values for hours to days following reflow. This phenomenon, first characterized in the experimental canine model, has more recently been documented in clinical instances of angina, following cardiac surgery, after angioplasty, and following successful reperfusion for the treatment of acute myocardial infarction. Considerable evidence indicates that calcium antagonists administered prior to coronary occlusion attenuate postischemic stunning in the canine model: verapamil, diltiazem, and amlodipine have been shown to restore contractile function to 50-100% of baseline values during the initial hours following relief of ischemia. Furthermore, both verapamil and nifedipine improved systolic contraction of stunned myocardium even when treatment was "delayed"--i.e., when the agents were administered 30 min after reflow had been established. This improved recovery of contractile function associated with calcium antagonist treatment may be due in part to the well-documented afterload reducing and coronary vasodilatory properties of these agents. However, as low doses of intracoronary nifedipine infused after reperfusion restored systolic contraction to 75-90% of baseline values in the absence of afterload reduction or increases in coronary blood flow, these data suggest that calcium antagonists may act in part by favorably modulating calcium flux within the stunned, previously ischemic myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Przyklenk
K
K
Heart Institute, Hospital of the Good Samaritan, Los Angeles, California 90017.
Kloner
R A
RA
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003327:Coronary Disease / Q000503:physiopathology* / Q000628:therapy; D004285:Dogs; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D015425:Myocardial Reperfusion; D013599:Systole / Q000187:drug effects
D002121:Calcium Channel Blockers