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(Circulation. 2001;104:1053.)
© 2001 American Heart Association, Inc.

Basic Science Reports

Ischemic Preconditioning Attenuates Cardiac Sympathetic Nerve Injury via ATP-Sensitive Potassium Channels During Myocardial Ischemia

Toshiro Miura, MD; Shuji Kawamura, MD; Hironari Tatsuno, MD; Yasuhiro Ikeda, MD; Shunsuke Mikami, MD; Hiroshi Iwamoto, MD; Takayuki Okamura, MD; Mitsuo Iwatate, MD; Masayasu Kimura, MD; Yuka Dairaku, MD; Tsuyoshi Maekawa, MD; Masunori Matsuzaki, MD

From the Department of Cardiovascular Medicine and the Department of Emergency Medicine (T. Maekawa), Yamaguchi University School of Medicine, Ube, Japan.

Correspondence to Toshiro Miura, MD, PhD, FAHA, Department of Cardiovascular Medicine, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, 755-8505, Yamaguchi, Japan. E-mail toshiro{at}po.cc.yamaguchi-u.ac.jp

Background— During myocardial ischemia, massive norepinephrine (NE) is released from the cardiac sympathetic nerve terminals, reflecting the sympathetic nerve injury. A brief preceding ischemia can reduce infarct size; this is known as ischemic preconditioning (PC). The effect of PC on sympathetic nerves, however, including its underlying mechanisms in dog hearts, has remained unclear. Thus, this study was designed to elucidate whether the activation of ATP-sensitive potassium (K_ATP) channels is involved in the mechanism of cardiac sympathetic nerve protection conferred by PC.

Methods and Results— Interstitial NE concentration was measured by the in situ cardiac microdialysis method in 45 anesthetized dogs. Five minutes of ischemia followed by 5 minutes of reperfusion was performed as PC. In the controls, the dialysate NE concentration (dNE) increased 15-fold after the 40-minute ischemia. PC decreased dNE at 40-minute ischemia by 59% (P<0.01), which was reversed by glibenclamide. A K_ATP channel opener, nicorandil (25 µg · kg^-1 · min^-1 IV), decreased dNE at 40 minutes of ischemia by 76% (P<0.01), which was also reversed by glibenclamide. During the PC procedure, no significant increase in dNE was detected, even with the uptake-1 inhibitor desipramine.

Conclusions— Cardiac sympathetic nerve injury during myocardial ischemia was attenuated by PC via the activation of K_ATP channels, but the trigger of the PC effect is unlikely to be NE release in dog hearts.

Key Words: ischemia • norepinephrine • nervous system, sympathetic • ion channels

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