Calcium antagonists and the stunned myocardium

Karin Przyklenk, Robert A. Kloner

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

"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. Although the precise mechanisms of action of these agents in the setting of transient ischemia/reperfusion remain unresolved, these experimental results raise the interesting possibility that calcium antagonists may provide a useful means of attenuating postischemic dysfunction in clinical instances of stunned myocardium.

Original languageEnglish
Pages (from-to)S93-S101
JournalJournal of Cardiovascular Pharmacology
Volume18
DOIs
StatePublished - 1991

Keywords

  • Diastolic relaxation
  • Diltiazem
  • Myocardial ischemia
  • Nifedipine
  • Reperfusion
  • Systolic contraction
  • Verapamil

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