Role of mitochondrial and sarcolemmal K(ATP) channels in ischemic preconditioning of the canine heart.
We tested whether mitochondrial or sarcolemmal ATP-sensitive K(+) (K(ATP)) channels play a key role in ischemic preconditioning (IP) in canine hearts. In open-chest beagle dogs, the left anterior descending artery was occluded four times for 5 min each with 5-min intervals of reperfusion (IP), occluded for 90 min, and reperfused for 6 h. IP as well as cromakalim and nicorandil (nonspecific K(ATP) channel openers) markedly limited infarct size (6.3 +/- 1.2, 8.9 +/- 1.9, and 7.2 +/- 1.6%, respectively) compared with the control group (40.9 +/- 4.1%). A selective mitochondrial K(ATP) channel blocker, 5-hydroxydecanoate, partially blunted the limitation of infarct size in the animals subjected to IP and those treated with cromakalim and nicorandil (21.6 +/- 3.8, 25.1 +/- 4.6, and 19.8 +/- 5.2%, respectively). A nonspecific K(ATP) channel blocker, glibenclamide, completely abolished the effect of IP (38.5 +/- 6.2%). Intracoronary or intravenous administration of a mitochondria-selective K(ATP) channel opener, diazoxide, at >100 micromol/l could only partially decrease infarct size (19.5 +/- 4.3 and 20.1 +/- 4.4%, respectively). In conclusion, mitochondrial and sarcolemmal K(ATP) channels independently play an important role in the limitation of infarct size by IP in the canine heart.
Sanada
S
S
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Kitakaze
M
M
Asanuma
H
H
Harada
K
K
Ogita
H
H
Node
K
K
Takashima
S
S
Sakata
Y
Y
Asakura
M
M
Shinozaki
Y
Y
Mori
H
H
Kuzuya
T
T
Hori
M
M
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003097:Collateral Circulation / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D019806:Cromakalim / Q000494:pharmacology; D003652:Decanoic Acids / Q000494:pharmacology; D003981:Diazoxide / Q000008:administration & dosage / Q000494:pharmacology; D004285:Dogs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D006880:Hydroxy Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D008929:Mitochondria, Heart / Q000187:drug effects / Q000502:physiology*; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology; D020108:Nicorandil / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000819:agonists / Q000502:physiology*; D012508:Sarcolemma / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D002121:Calcium Channel Blockers; D003652:Decanoic Acids; D006880:Hydroxy Acids; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014665:Vasodilator Agents; D019806:Cromakalim; D020108:Nicorandil; C052853:5-hydroxydecanoic acid; D000255:Adenosine Triphosphate; D003981:Diazoxide