Cardioprotection by Remote Ischemic Preconditioning is Blocked in the Aged Rat Heart in Vivo

Abstract

Objectives: In animal studies, remote ischemic preconditioning (RIPC) is a powerful tool to protect the heart from ischemia and reperfusion injury. Unfortunately, this effect was not seen consistently in recent large clinical trials. Aging was shown to be a confounding factor for the effect of direct preconditioning in experimental studies, but whether aging also can influence the effect of RIPC and thus be responsible for the contradictory clinical effect is unknown. The aim of this study was to investigate whether the cardioprotective effect of RIPC was abolished by aging.

Design: Randomized, prospective, blinded laboratory investigation.

Setting: Experimental laboratory.

Participants: Male Wistar rats.

Interventions: Anesthetized young (Y, 2-3 months) and aged (A, 22-24 months) male Wistar rats were randomized to 4 groups (n = 6 per group). Control animals (Y-Con and A-Con) were not treated further; RIPC groups (Y-RIPC and A-RIPC) received 4 cycles of 5 minutes of bilateral hind limb ischemia interspersed with 5 minutes reperfusion before myocardial ischemia and reperfusion. All animals underwent 25 minutes of regional myocardial ischemia and 120 minutes of reperfusion. At the end of reperfusion, infarct size was determined by TTC staining.

Measurements and main results: In the control group of young rats, infarct size was 56±9% of the area at risk. RIPC reduced infarct size to 31±9% (p<0.05 v Y-Con). Cardioprotection by RIPC was abolished completely in the aged rat heart (A-RIPC: 62±8%, A-Con: 63±4%; ns).

Conclusions: The results of the authors' study showed that cardioprotection induced by remote ischemic preconditioning was blocked in the aged rat heart.

Keywords: aging; conditioning; myocardial infarction; remote ischemic preconditioning; reperfusion injury.