Cardioprotective effect of intracoronary zinc administration in isolated rat hearts during ischemia-reperfusion following intermittent hypoxia exposure in vivo.

INTRODUCTION

Zinc is an essential trace element with antioxidant and signaling functions critical to cardiac physiology. This study investigated the role of zinc in myocardial ischemia-reperfusion (IR)-induced cardiac damage using a rat model, and whether zinc deficiency induced by intermittent hypoxia (IH) exacerbates cardiac injury.

METHODS

Regional IR was performed in isolated rat hearts, and zinc concentrations were measured in coronary effluents. Plasma zinc status was assessed following 14- or 35-day IH exposure (1-min cycles alternating 21% and 5% FiO₂, 8 h/day). The cardioprotective effects of intracoronary zinc administration with the ionophore pyrithione were evaluated based on arrhythmias, infarct size, and contractile recovery.

RESULTS

Myocardial IR induced significant zinc release upon reperfusion (615.7 ± 78.2 nM vs. 374.5 ± 40.3 nM pre-reperfusion, P < 0.01). Zinc administration during reperfusion reduced arrhythmia duration (358.0 ± 61.7 sec vs. 559.9 ± 31.6 sec, P < 0.01) and improved myocardial recovery. IH exposure led to reduced plasma zinc levels (10.3 ± 0.5 µM vs. 13.0 ± 1.2 µM, P = 0.057) and significantly increased infarct size following IR (43.9 ± 4.2% vs. 29.2 ± 4.3%, P < 0.05). Zinc-pyrithione treatment during reperfusion abolished the deleterious effects of IH on infarct size.

DISCUSSION: IH-induced zinc deficiency exacerbates cardiac vulnerability to IR injury, while zinc restoration through targeted administration mitigates this damage. Zinc's protective effects may involve antioxidant action, calcium homeostasis, and signaling modulation.

CONCLUSION

Zinc plays a critical role in limiting IR-induced cardiac damage. Zinc supplementation during reperfusion may offer therapeutic benefit, particularly in conditions associated with chronic IH, such as obstructive sleep apnea.