Calpain inhibitor-1 reduces infarct size and DNA fragmentation of myocardium in ischemic/reperfused rat heart.
Myocardial ischemia/reperfusion activates a calcium-dependent protease, calpain, in the ischemic myocytes. It is not known whether calpain is involved in the mechanism of ischemia/reperfusion injury in hearts. Thus the purpose of this study was to clarify the effect of a selective calpain inhibitor (CAI) on infarct size and the extent of DNA damage in ischemic/reperfused rat hearts. Rats were divided in four groups (n = 7 each). In saline group, 0.3 ml of saline was administered (i.v.) 10 min before 30-min coronary occlusion followed by 6-h reperfusion. In vehicle group, 0.3 ml of 10% dimethyl sulfoxide (DMSO) was administered 10 min before the 30-min ischemia. CAI (0.5 mg/kg) was administered 10 min before the 30-min ischemia (CAI-A group) and 10 min before the 6-h reperfusion period (CAI-B group). Infarct size was detected with triphenyl tetrazolium chloride, and DNA fragmentation was detected by agarose gel electrophoresis and by in situ nick end labeling (ISEL). Infarct size was significantly smaller in the CAI-A group compared with the vehicle group (13+/-9% vs. 48+/-12%; p < 0.01), and the incidence of ISEL-positive myocyte nuclei in the subendocardial region was significantly reduced in the CAI-A group compared with the vehicle group (26+/-3% vs. 59+/-6%; p < 0.01). However, the effects of CAI in CAI-B group were not significant. Activation of calpain is involved in the mechanism of ischemia/reperfusion injury, and the preischemic administration of CAI was effective in reducing myocardial infarct size and the DNA damage of the myocytes in ischemic/reperfused rat heart.
Iwamoto
H
H
The Second Department of Internal Medicine, Yamaguchi University School of Medicine, Ube, Japan.
Miura
T
T
Okamura
T
T
Shirakawa
K
K
Iwatate
M
M
Kawamura
S
S
Tatsuno
H
H
Ikeda
Y
Y
Matsuzaki
M
M
D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects; D004249:DNA Damage; D053938:DNA Fragmentation / Q000187:drug effects*; D004587:Electrophoresis, Agar Gel; D006023:Glycoproteins / Q000494:pharmacology / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000235:genetics / Q000473:pathology*
D006023:Glycoproteins; C039304:calpain inhibitors