0228 : Beneficial effects of zinc on incidence and severity of ventricular reperfusion arrhythmias

Abstract

Intermittent hypoxia (IH), a major component of obstructive sleep apnea syndrome (OSA), causes several cardiovascular alterations such as hypertension, increased infarct size and ventricular arrhythmias. Indeed, IH exposure enhances the incidence of severe ventricular arrhythmias during both ischemia and reperfusion. Oxidative stress is a common feature behind the deleterious effects of both IH and ischemia-reperfusion on the myocardium. Zinc is an essential metal associated with numerous proteins and playing a vital role in various cellular functions. Its homeostasis is closely linked to the cell redox state since zinc release by oxidation can induce protein conformation changes. The resulting modification in protein activity could thus be restored by zinc administration. Thereby, the effects of zinc supplementation were investigated in isolated perfused rat hearts presenting severe ventricular reperfusion arrhythmias following a 15-min regional ischemia. Incidence, severity and duration of ventricular arrhythmias were assessed during the first 10min of reperfusion. Three groups were compared in which zinc (pyrithione form, Zn-Pyr, 2.10-5M in DMSO), DMSO (vehicle) or pyrithione sodium (Na-Pyr) was added to the Krebs upon reperfusion. Reperfusion with Zn-Pyr significantly enhanced survival (40%) compared to DMSO or Na-Pyr (6%) (n=17 per group, p<0.05). Moreover, the time spent in sinus rhythm was significantly increased in the Zn-Pyr group compared to other groups (p<0.01). Accordingly, the duration of ventricular tachycardia/fibrillation was significantly decreased in the Zn-Pyr group (p<0.05). Therefore, zinc administration during reperfusion improves survival in response to a severe ischemic insult. Zinc supplementation upon myocardial reperfusion procedures could thus represent a valuable approach to prevent the occurrence of arrhythmias and could be of interest in the prevention of IHand OSA-related ventricular arrhythmias.