Ischemic preconditioning is not cardioprotective in senescent human myocardium

Cellular and functional changes secondary to aging could impair myocardial tolerance to ischemia and affect the heart's response to ischemic preconditioning.

We investigated the impact of cardiac aging on preconditioning in right atrial trabeculae of adult patients (< or = 55 years) and senescent patients (> or = 70 years) with coronary artery disease. Specimens were subjected to 30 minutes of simulated ischemia (hypoxic substrate-free superfusion) with and without 5 minutes of ischemic pretreatment. Postischemic contractile recovery was measured and expressed as percentage of base line force values.

During the reoxygenation period, trabeculae of adult patients but not those of senescent patients improved after ischemic preconditioning. After 40 minutes of reoxygenation, preconditioned adult trabeculae developed 57% +/- 5% of their preischemic force (nonpreconditioned control 44% +/- 5%, p < 0.01), senescent trabeculae recovered to 44% +/- 4% (control 45% +/- 3%). Especially myocardium from adult patients with Canadian Cardiovascular Society (CCS) stage III angina pectoris treated with ACE inhibitors recovered well (70% +/- 7%; control 50% +/- 8%, p < 0.01), contrasting with trabeculae from patients with CCS stage II angina (44% +/- 5%; control 40% +/- 10%). Ischemia-inducible Hsp70 (human heat shock protein) was additionally measured after reoxygenation. Total Hsp70 mRNA was elevated in preconditioned myocardium along with its contractile recovery (r = 0.33, p = 0.07). Because the control transcription, analyzing 18S rRNA and beta-actin, was reduced by ischemia but recovered in preconditioned trabeculae, relative Hsp70 mRNA was not altered.

Our data indicate that ischemic preconditioning has no beneficial effect on the postischemic functional recovery of senescent human myocardium.