TY - JOUR
T1 - Role of mitochondrial and sarcolemmal KATP channels in ischemic preconditioning of the canine heart
AU - Sanada, Shoji
AU - Kitakaze, Masafumi
AU - Asanuma, Hiroshi
AU - Harada, Kengo
AU - Ogita, Hisakazu
AU - Node, Koichi
AU - Takashima, Seiji
AU - Sakata, Yasuhiko
AU - Asakura, Masanori
AU - Shinozaki, Yoshiro
AU - Mori, Hidezo
AU - Kuzuya, Tsunehiko
AU - Hori, Masatsugu
PY - 2001
Y1 - 2001
N2 - We tested whether mitochondrial or sarcolemmal ATP-sensitive K′ (KATP) 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 KATP 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 KATP 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 KATP channel blocker, glibenclamide, completely abolished the effect of IP (38.5 ± 6.2%). Intracoronary or intravenous administration of a mitochondria-selective KATP channel opener, diazoxide, at >100 μmol/l could only partially decrease infarct size (19.5 ± 4.3 and 20.1 ± 4.4%, respectively). In conclusion, mitochondrial and sarcolemmal KATP channels independently play an important role in the limitation of infarct size by IP in the canine heart.
AB - We tested whether mitochondrial or sarcolemmal ATP-sensitive K′ (KATP) 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 KATP 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 KATP 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 KATP channel blocker, glibenclamide, completely abolished the effect of IP (38.5 ± 6.2%). Intracoronary or intravenous administration of a mitochondria-selective KATP channel opener, diazoxide, at >100 μmol/l could only partially decrease infarct size (19.5 ± 4.3 and 20.1 ± 4.4%, respectively). In conclusion, mitochondrial and sarcolemmal KATP channels independently play an important role in the limitation of infarct size by IP in the canine heart.
KW - 5-hydroxydecanoate
KW - Diazoxide
KW - Infarct size
UR - http://www.scopus.com/inward/record.url?scp=0035018245&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035018245&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.2001.280.1.h256
DO - 10.1152/ajpheart.2001.280.1.h256
M3 - Article
C2 - 11123240
AN - SCOPUS:0035018245
VL - 280
SP - H256-H263
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6135
IS - 1 49-1
ER -