Loss of preconditioning by attenuated activation of myocardial ATP-sensitive potassium channels in elderly patients undergoing coronary angioplasty.
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.


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.
Lee
Tsung-Ming
TM
National Taiwan University College of Medicine, Department of Internal Medicine, Cardiology Section, National Taiwan University Hospital, Taipei, Taiwan.
Su
Sheng-Fang
SF
Chou
Tsai-Fwu
TF
Lee
Yuan-Teh
YT
Tsai
Chang-Her
CH
D018528:ATP-Binding Cassette Transporters; D000328:Adult; D000368:Aged; D000375:Aging; D015906:Angioplasty, Balloon, Coronary; D002637:Chest Pain / Q000175:diagnosis; D003327:Coronary Disease / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*; D004562:Electrocardiography; D005260:Female; D005905:Glyburide / Q000627:therapeutic use; D006439:Hemodynamics; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D054086:KATP Channels; D019344:Lactic Acid / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D020108:Nicorandil / Q000627:therapeutic use; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000819:agonists / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying
D018528:ATP-Binding Cassette Transporters; D054086:KATP Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; D020108:Nicorandil; D019344:Lactic Acid; D005905:Glyburide