The effect of zinc on reperfusion arrhythmias in the isolated perfused rat heart.
Considerable evidence suggests that free radicals engendered by redox-active metals, particularly iron and copper, are causative agents in reperfusion injury following ischemia. This study demonstrates that perfusion of the isolated rat heart with a buffer containing zinc, a non-redox active metal similar to copper in its coordination chemistry, inhibits the development of ventricular arrhythmias during reperfusion. Zinc was employed as the bishistidine complex, Zn--His2, to maintain solubility and permeability. Zn--His2 exerted an antiarrhythmic activity as hearts spent a longer time in normal sinus rhythm and a shorter time in ventricular fibrillation during reperfusion following 10 min of regional ischemia. However, Zn--His2 also produced a negative inotropic and chronotropic effect, evident during equilibration and ischemia. In the course of experiments which began in Israel and continued in the U.S. it was necessary to use two different sources of rats. Hearts from the two sources manifested different sensitivities to the concentrations of Zn--His2, although their physiological effects were similar. Differential activity responses were noted for antiarrhythmic activity, negative inotropic and chronotropic properties, and toxicity. In both groups of untreated hearts the incidence of ventricular fibrillation after ischemia was 100%. Ventricular fibrillation was reduced to 17% at 37.5 microM Zn--His2 in the U.S.-bred rat hearts and to 9% at 200 microM Zn--His2 in those from Israel. These changes in Zn--His2 treated animals were accompanied by a decrease in lactate dehydrogenase release from the myocardium during reperfusion. None of the protective effects was due to histidine alone. These results indicate that zinc prevents ventricular arrhythmias during reperfusion following regional ischemia and may prevent membrane damage, possibly, by reduction of free radical formation.
Powell
S
S
Department of Cellular Biochemistry, Hebrew University of Jerusalem, Hadassah School of Medicine, Israel.
Saltman
P
P
Uretzky
G
G
Chevion
M
M
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D003627:Data Interpretation, Statistical; D005609:Free Radicals; D006439:Hemodynamics / Q000187:drug effects; D006639:Histidine / Q000494:pharmacology; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D051381:Rats; D011919:Rats, Inbred Strains; D015032:Zinc / Q000494:pharmacology*
D005609:Free Radicals; D006639:Histidine; D007770:L-Lactate Dehydrogenase; D015032:Zinc