Loss of Preconditioning by Attenuated Activation of Myocardial ATP-Sensitive Potassium Channels in Elderly Patients Undergoing Coronary Angioplasty

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Abstract
Background — The ischemic preconditioning response among elderly patients is known to be lower than in adult patients. Since mitochondrial ATP-sensitive potassium (K ATP ) channels exert preconditioning effects, we undertook this study to determine whether this attenuated activation of K ATP channels influences the reduced responsiveness of elderly patients to ischemic preconditioning. Methods and Results — Fifty-six patients undergoing angioplasty for a major epicardial coronary artery were randomly allocated to either an ischemic preconditioning group, a nicorandil (an agonist of K ATP channels) group, or a glibenclamide (an antagonist of K ATP channels), group based on their age: adult groups (n=26; age, ≤55 years; mean age, 45±5 years) and elderly groups (n=30; age, ≥65 years; mean age, 71±3 years). Ischemic preconditioning with a 120-second coronary occlusion significantly lowered the ischemic burden assessed by ST-segment shift, chest pain score, and myocardial lactate extraction ratios in the adult group. This did not occur in the elderly group. The impaired preconditioning responsiveness in the elderly patients was reversed by nicorandil administration or an ischemic period lengthened to 180 seconds. However, nicorandil-induced cardioprotection was abolished by administering glibenclamide in both the adult and elderly groups. Conclusions — The present study demonstrates that preconditioning significantly enhances the tolerance of the heart to subsequent ischemia in adults but not in senescent patients. Since prolonged ischemia and nicorandil are able to mimic preconditioning and can reverse impaired responsiveness, impaired preconditioning of the aged heart appears to be due to an attenuated activation of K ATP channels.