Pathophysiology of acute ischemia: Potential targets for antiarrhythmic drugs

  • André G. Kléber

Summary

The electrophysiological changes during acute myocardial ischemia show a characteristic time-dependence. The first change to be observed is a reduction in resting membrane potential and a decrease in upstroke rate of rise, amplitude, and duration of the transmembrane action potential. These changes are closely related to the loss of potassium from ischemic cells and to metabolic acidosis. At a later stage (approximately 15 min after arrest of perfusion) electrical cell-to-cell uncoupling takes place. The associated arrhythmias (ventricular tachycardia, ventricular fibrillation) are due to circus movement reentry and show an early (lA arrhythmias) and a later (1B arrhythmias) peak of incidence. Both focal and reentrant mechanisms are responsible for initiating the arrhythmias in the ischemic border zone.

The complexity of the mechanisms of antiarrhythmic drug action in acute ischemia is illustrated with three examples. In the case of lidocaine, the effect on reentrant arrhythmias is relatively well explained by the inhibitory effect on Na+channels and the consequent preferential depression of action potentials elicited from depolarized ischemic cells. Ca++entry blockade exerts multiple actions on ischemic ionic and electrical changes. Sulfonylureas are an example of drugs with a metabolic target in addition to their effect to inhibit ATP-sensitive K+ channels.

Keywords

Dioxide Magnesium Depression Ischemia Lactate 

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Copyright information

© Dr. Dietrich Steinkopff Verlag GmbH & Co. KG, Darmstadt 1994

Authors and Affiliations

  • André G. Kléber
    • 1
  1. 1.Department of PhysiologyUniversity of BernBernSwitzerland

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