title: Ischemic preconditioning attenuates cardiac sympathetic nerve injury via ATP-sensitive potassium channels during myocardial ischemia.
abstract: 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.
  
  
  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 microg. 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.
authors.affiliation: Department of Cardiovascular Medicine, Yamaguchi University School of Medicine, Ube, Japan. toshiro@po.cc.yamaguchi-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Miura
authors.forename: S
authors.initials: S
authors.lastname: Kawamura
authors.forename: H
authors.initials: H
authors.lastname: Tatsuno
authors.forename: Y
authors.initials: Y
authors.lastname: Ikeda
authors.forename: S
authors.initials: S
authors.lastname: Mikami
authors.forename: H
authors.initials: H
authors.lastname: Iwamoto
authors.forename: T
authors.initials: T
authors.lastname: Okamura
authors.forename: M
authors.initials: M
authors.lastname: Iwatate
authors.forename: M
authors.initials: M
authors.lastname: Kimura
authors.forename: Y
authors.initials: Y
authors.lastname: Dairaku
authors.forename: T
authors.initials: T
authors.lastname: Maekawa
authors.forename: M
authors.initials: M
authors.lastname: Matsuzaki
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D003326:Coronary Circulation; D003891:Desipramine / Q000494:pharmacology; D015314:Dialysis Solutions / Q000737:chemistry; D004110:Diltiazem / Q000494:pharmacology; D004285:Dogs; D005905:Glyburide / Q000494:pharmacology; D006321:Heart / Q000294:innervation; D006439:Hemodynamics; D019194:Ischemic Preconditioning; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D020108:Nicorandil / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D015221:Potassium Channels / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000473:pathology*; D013997:Time Factors
chemical_list: D015314:Dialysis Solutions; D015221:Potassium Channels; D020108:Nicorandil; D000255:Adenosine Triphosphate; D004110:Diltiazem; D005905:Glyburide; D003891:Desipramine; D009638:Norepinephrine