Ischemic preconditioning maintains cardioprotection in aging normotensive and spontaneously hypertensive rats

Abstract

We determined whether ischemic preconditioning could reduce infarct size and improve cardiac function in both aging normotensive Wistar–Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The left anterior descending coronary artery was occluded for 1 h followed by 3 h reperfusion in aging (∼16 months old) SHR rats and age-matched WKY rats. Hearts were either preconditioned or not (control group) prior to 1 h of coronary artery occlusion. The preconditioning regimen consisted of three cycles of 3 min occlusion followed by 5 min reperfusion applied prior to the subsequent 1 h occlusion. In WKY (n = 12 each group), the risk zone was similar in the control (51 ± 2%) and preconditioned group (46 ± 2%; p = 0.1). Preconditioning significantly reduced infarct size (as a percentage of the ischemic risk zone) (24 ± 6%) compared to controls (51 ± 5%; p = 0.0026). In SHR rats (n = 9 each group), the risk zone was smaller in the preconditioning group (41 ± 3%) than in the control group (51 ± 3%; p = 0.035). Infarct size (as % of ischemic risk zone) was also significantly reduced in the preconditioned group (13 ± 4%) compared to controls (62 ± 5%; p < 0.0001). For both WKY and SHR rats, for any sized risk zone the infarct size was smaller in preconditioned hearts compared with the control hearts. Preconditioning improved aspects of LV function during ischemia and reperfusion phase in SHR rats, but these benefits were not observed in the WKY rats. Preconditioning maintains powerful cardioprotection in aging normotensive hearts as well as aging hypertrophied hearts.

Introduction

Episodes of brief exposure to ischemia/reperfusion prior to sustained ischemia are able to enhance the ability of the heart to withstand a subsequent sustained ischemic insult, a phenomenon known as ischemic preconditioning (Murry et al., 1986). Whether the beneficial effects of ischemic preconditioning are retained in aging myocardium is controversial. Some studies showed that cardioprotection with ischemic preconditioning was lost in the aging heart (Boengler et al., 2007, Fenton et al., 2000, Schulman et al., 2001). However, other studies demonstrated that the efficacy of ischemic preconditioning was conserved in senescent myocardium (Burns et al., 1996, Przyklenk et al., 2001).

In humans, aging is often associated with hypertension. The co-existence of both aging and prolonged hypertension might modify the response of the myocardium to ischemic preconditioning. Therefore investigating whether ischemic preconditioning also protects chronically hypertensive myocardium is a clinically relevant issue. While some investigations suggest that ischemic preconditioning can protect hypertrophied myocardium in hypertensive animals (Boutros and Wang, 1995, Randall et al., 1997, Speechly-Dick et al., 1994), Ebrahim et al. (2007) recently demonstrated that efficacy of ischemic preconditioning was lost in Langendorff-perfused aging hypertensive rat hearts. However, the efficacy of ischemic preconditioning in aging hypertensive hearts in an in vivo model of regional ischemia remains to be determined. The purpose of this study was to determine whether ischemic preconditioning can reduce myocardial infarct size and improve cardiac function in hearts from aging spontaneously hypertensive rats (SHR) as well as hearts from normotensive aging Wistar–Kyoto rats (WKY).

To the best of our knowledge this is the first study aimed at assessing the efficiency of ischemic preconditioning in an in vivo model of acute myocardial infarction in aging SHR rats.