Effects of extracellular magnesium manipulation on reperfusion-induced arrhythmias and myocardial ion shifts in isolated ischemic reperfused rat hearts

A. Tosaki, P. Szerdahelyi, R. M. Engelman, D. K. Das

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Abstract

Isolated rat hearts were subjected to global ischemia followed by reperfusion, and a reduction in the incidence of reperfusion-induced ventricular fibrillation and ventricular tachycardia was brought about by increasing the extracellular Mg concentration in the perfusion buffer. Thus the incidence of ventricular fibrillation was reduced from its control value of 100% in 1.2 mM Mg to 83% by 2.4 mM Mg (P = N.S.), to 42% by 3.6 mM Mg (P < .05), to 17% by 4.8 mM Mg (P < .001) and to 17% by 9.6 mM Mg (P < .001). The corresponding values for ventricular tachycardia were 100% (control, 1.2 mM Mg) vs. 92% (P = N.S.), 50% (P < .05), 25% (P < .01) and 25% (P < .01), respectively. In further studies, extracellular Ca was reduced by 50% (1.2 mM) in the perfusion buffer just before ischemia and during reperfusion. The incidence of ventricular fibrillation was reduced from its control value of 83% in 1.2 mM Mg to 75% by 1.8 mM Mg (P = N.S.), to 33% by 2.4 mM Mg (P < .05), to 17% by 3.6 mM Mg (P < .01) and to 8% by 4.8 mM Mg (P < .01). The incidence of ventricular tachycardia followed the same pattern. Myocardial Na, K, Ca and Mg were measured by atomic absorption spectrophotometer after the removal of ions from the extracellular space. In controls, 30 min of ischemia resulted in 3- and 4-fold accumulation of myocardial Na and Ca, respectively, and during reperfusion these values were similar to the values for 30-min ischemia. Elevated extracellular Mg attenuated ischemia and reperfusion-induced myocardial Na and Ca gain in both the 2.4 and the 1.2 mM extracellular Ca-perfused groups. Thirty minutes of ischemia followed by reperfusion resulted in a 50% decrease in both myocardial K and myocardial Mg. When extracellular Mg was increased in the perfusate, myocardial K and Mg losses were reduced. Our results show that the manipulation of Mg in the perfusate can modify both the ischemia and the reperfusion-induced ion shifts and protect the heart against arrhythmias.

Original languageEnglish
Pages (from-to)1045-1053
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume267
Issue number3
Publication statusPublished - Dec 1 1993

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ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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