Blockade of ATP-sensitive K+ channel abolishes the anti-ischemic effects of isoflurane in dog hearts.
BACKGROUND
Although isoflurane is reported to have a protective effect against ischemic damage on the myocardium, the mechanisms of this effect are not clear. Activation of adenosine triphosphate sensitive potassium (KATP) channels is indicated to protect myocardium during ischemia. Thus, it was hypothesized that if isoflurane could activate KATP channels, blockade of KATP channels would decrease its cardioprotective effect.


METHODS
Mongrel dogs, anesthetized with morphine, urethane, and chloralose, were subjected to 15 min of left anterior descending coronary artery occlusion followed by 60 min reperfusion. The dogs were divided into three groups: the control group (n = 8), ISO group (n = 8) and ISOGC group (n = 8). In the ISO and ISOGC groups, 1 MAC of isoflurane was administrated during ischemia and reperfusion. In the ISOGC group, 0.3 mg/kg of glibenclamide, the KATP channel blocker, was given 45 min before ischemia. Full-thickness samples of myocardium were obtained and the concentrations of adenosine monophosphate, adenosine diphosphate, adenosine triphosphate (ATP), creatine phosphate and lactate in the endocardial portion of the myocardium were measured.


RESULTS
The ischemia-reperfusion caused a 25.4% and 27.6% reduction of myocardial ATP in the control and ISOGC groups, respectively. In contrast, the ISO group showed only 11.0% reduction of ATP, which was significantly lower compared to the other groups (P < 0.01).


CONCLUSIONS
Our results shows that blockade of the KATP channel abolishes cardioprotective effects of isoflurane in myocardial ischemia-reperfusion. The KATP channel may play a role in the ATP-sparing effect of isoflurane.
Nakayama
M
M
Department of Anesthesiology, Sapporo Medical University School of Medicine, Japan.
Fujita
S
S
Kanaya
N
N
Tsuchida
H
H
Namiki
A
A
D000255:Adenosine Triphosphate / Q000378:metabolism*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D017202:Myocardial Ischemia / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology
D018685:Anesthetics, Inhalation; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D007530:Isoflurane; D005905:Glyburide