EFFECTS OF EXTRACELLULAR MAGNESIUM MANIPULATION ON REPERFUSION-INDUCED ARRHYTHMIAS AND MYOCARDIAL ION SHIFTS IN ISOLATED ISCHEMIC-REPERFUSED RAT HEARTS
A. Tosaki et al., EFFECTS OF EXTRACELLULAR MAGNESIUM MANIPULATION ON REPERFUSION-INDUCED ARRHYTHMIAS AND MYOCARDIAL ION SHIFTS IN ISOLATED ISCHEMIC-REPERFUSED RAT HEARTS, The Journal of pharmacology and experimental therapeutics, 267(3), 1993, pp. 1045-1053
Isolated rat hearts were subjected to global ischemia followed by repe
rfusion, and a reduction in the incidence of reperfusion-induced ventr
icular fibrillation and ventricular tachycardia was brought about by i
ncreasing the extracellular Mg concentration in the perfusion buffer.
Thus the incidence of ventricular fibrillation was reduced from its co
ntrol 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 tachyca
rdia 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, ex
tracellular Ca was reduced by 50% (1.2 mM) in the perfusion buffer jus
t before ischemia and during reperfusion. The incidence of ventricular
fibrillation was reduced from its control value of 83% in 1.2 mM Mg t
o 75% by 1.8 mM Mg (P = N.S.), to 33% by 2.4 mM Mg (P < .05), to 17% b
y 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 a
nd Ca, respectively, and during reperfusion these values were similar
to the values for 30-min ischemia. Elevated extracellular Mg attenuate
d ischemia and reperfusion-induced myocardial Na and Ca gain in both t
he 2.4 and the 1.2 mM extracellular Ca-perfused groups. Thirty minutes
of ischemia followed by reperfusion resulted in a 50% decrease in bot
h 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.