Characterization of the Antiarrhythmic Effect of the Trace Element Zinc and its Potential Relationship to Inhibition of Oxidative Stress

W
e and others have proposed that the trace element zinc can antagonize copper-and/or iron- mediated site-specific reactive oxygen intermediate formation, a process thought to be involved in reperfusion injury. The purpose of this study was further examine the effect of zinc on reperfusion arrhytmias in an in vitro model of regional ischemia, to characterize the kinetics of this effect, and to evaluate the potential role of inhibition of oxidative stress. Rat hearts were perfused in the Langendorff mode with a standard Krebs-Henseleit buffer. Hearts, perfused with buffer containing increasing concentrations of zinc-bis-histidinate, showed decreased incidence and duration of ventricular fibrillation. A pharmacokinetic profile was determined by altering the preischemic loading period. Hearts were perfused with 20 mcM zinc for up to 20 min. preischemic or perfused with zinc during the ischemic and reperfusion periods alone. As the duration of the preiscxhemic zinc load increased there was a significant decrease in the incidence and duration of VF, and a concomitant increase in incidence and duration of NSR. Pacing experiments were conducted to account for the negative chronotropic effect of zinc. Using salicylate as a free radical probe, it was determined that preischemic perfusion with 20 mcM zinc decreased background 'OH formation after regional ischemia. These results demonstrate that zinc decreases reperfusion injury, possibly through a mechanism involving decreased formation of reactive oxygen intermediates.

LT Aiuto, SR Powell, J Trace Elem Exp Med 1995;8:173-182.

Copyright © 2003 Anamol Laboratories Ltd.

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