Cardioprotective effects of nicorandil in rabbits anaesthetized with halothane: potentiation of ischaemic preconditioning via KATP channels.
1. The roles of ATP-sensitive K+ channels (KATP channels) in ischaemic or pharmacological preconditioning in the rabbit heart remain unclear. Infarct limitation by ischaemic preconditioning was abolished by the KATP channel blocker glibenclamide under ketamine/xylazine anaesthesia, but not under anaesthesia induced by pentobarbital. Infarct limitation by the KATP channel opener pinacidil was detected under ketamine/xylazine anaesthesia, but not under pentobarbital anaesthesia. Thus, these effects appear to be anaesthetic dependent. 2. In the present study, we examined whether nicorandil (a KATP channel opener nitrate) exhibits cardioprotective actions under halothane anaesthesia, another commonly used volatile anaesthetic. Control animals were subjected to 40 min coronary occlusion and 120 min reperfusion. Before 40 min ischaemia, the nicorandil group received nicorandil (100 microg/kg per min, i.v., for 10 min), the 5' preconditioning (PC) group received 5 min ischaemia/20 min reperfusion, the 2.5'PC group received 2.5 min preconditioning ischaemia/20 min reperfusion, the nicorandil +2.5'PC group received both nicorandil and 2.5 min ischaemia/20 min reperfusion, the nicorandil +2.5'PC + 5-hydroxydecanoate (5HD) group received both nicorandil and 2.5 min ischaemia/20 min reperfusion in the presence of 5-hydroxydecanoate (5HD; a KATP blocker) and the 5HD group received 5 mg/kg, i.v., 5HD alone. Myocardial infarct size in control (n = 7), nicorandil (n = 5), 5'PC (n = 8), 2.5'PC (n = 5), nicorandil + 2.5'PC (n = 5), nicorandil + 2.5'PC + 5HD (n = 5) and 5HD (n = 4) groups averaged 44.4 +/- 3.6, 41.7 +/- 5.7, 17.8 +/- 3.2,* 34.1 +/- 4.8, 21.3 +/- 4.2,* 39.1 +/- 5.6 and 38.9 +/- 5.0% of the area at risk, respectively (*P <0.05 vs control). 3. Thus, nicorandil alone did not have an infarct size-limiting effect in halothane-anaesthetized rabbits. However, the results suggest that even when nicorandil alone does not demonstrate a direct cardioprotective effect, it may enhance ischaemic preconditioning via KATP channels. Key words: ATP-sensitive K+ (KATP) channel, ischaemic preconditioning, myocardial infarction, nicorandil, rabbit.
Nakae
I
I
First Department of Internal Medicine, Medical Coordination Center, Shiga University of Medical Science, Seta, Otsu, Japan. mitunami@sums.shiga-med.ac.jp
Takaoka
A
A
Mitsunami
K
K
Yabe
T
T
Ito
M
M
Masayuki
Takahashi
Matsumoto
T
T
Omura
T
T
Yokohama
H
H
Kinoshita
M
M
D018528:ATP-Binding Cassette Transporters; D000769:Anesthesia, Inhalation / Q000379:methods; D018685:Anesthetics, Inhalation / Q000008:administration & dosage*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D003652:Decanoic Acids / Q000494:pharmacology; D006221:Halothane / Q000008:administration & dosage*; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006880:Hydroxy Acids / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial; D054086:KATP Channels; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000517:prevention & control*; D020108:Nicorandil / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology*
D018528:ATP-Binding Cassette Transporters; D018685:Anesthetics, Inhalation; D000889:Anti-Arrhythmia Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; D054086:KATP Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D014665:Vasodilator Agents; C092520:uK-ATP-1 potassium channel; D020108:Nicorandil; C052853:5-hydroxydecanoic acid; D006221:Halothane