H. Iwamoto et al., Calpain inhibitor-1 reduces infarct size and DNA fragmentation of myocardium in ischemic/reperfused rat heart, J CARDIO PH, 33(4), 1999, pp. 580-586
Citations number
45
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Myocardial ischemia/reperfusion activates a calcium-dependent protease, cal
pain, in the ischemic myocytes. It is not known whether calpain is involved
in the mechanism of ischemia/reperfusion injury in hearts. Thus the purpos
e 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 r
at 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 occl
usion followed by 6-h reperfusion. In vehicle group, 0.3 mi 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 w
as detected with triphenyl tetrazolium chloride, and DNA fragmentation was
detected by agarose gel electrophoresis and by in situ nick end labeling (I
SEL). Infarct size was significantly smaller in the CAI-A,group compared wi
th the vehicle group(13 +/- 9% vs. 48 +/- 12%; p < 0.01), and the incidence
of ISEL-positive myocyte nuclei in the subendocardial region was significa
ntly reduced in the CAI-A group compared with the vehicle group (26 +/- 38
vs. 59 +/- 6%; p < 0.01). However, the effects of CAI in CAI-B group were n
ot significant. Activation of calpain is involved in the mechanism of ische
mia/reperfusion injury, and the preischemic administration of CAT was effec
tive in reducing myocardial infarct size and the DNA damage of the myocytes
in ischemic/reperfused rat heart.