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(Circulation. 2002;105:334.)
© 2002 American Heart Association, Inc.

Clinical Investigation and Reports

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

Tsung-Ming Lee, MD; Sheng-Fang Su, PhD; Tsai-Fwu Chou, MD; Yuan-Teh Lee, MD, PhD; Chang-Her Tsai, MD, PhD

From National Taiwan University College of Medicine, Departments of Internal Medicine (T.-M.L., Y.-T.Y.) and Surgery (C.-H.T.), Cardiology Section, National Taiwan University Hospital, Taipei, Taiwan; the Department of Clinical Pharmacy (S.-F.S.), College of Medicine, National Cheng Kung University, Tainan, Taiwan; and the Department of Surgery (T.-F.C.), Municipal Jen-Ai Hospital, Taipei, Taiwan.

Correspondence to Dr Yuan-Teh Lee, Department of Internal Medicine, Cardiology Section, National Taiwan University Hospital, 7, Chung-Shan S. RD., Taipei, Taiwan, 10002. E-mail ytlee{at}ha.mc.ntu.edu.tw

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.

Key Words: coronary disease • ion channels • ischemia • reperfusion

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