[Amelioration of ischemia- and reperfusion-induced myocardial injury by the selective estrogen receptor modulator, raloxifene, in the canine heart].
BACKGROUND
17 beta-estradiol reduces myocardial infarct size which is mediated by nitric oxide (NO) and the opening of Ca (2+)-activated K+ (KCa) channels. Raloxifene, a selective estrogen receptor modulator, demonstrates acute coronary artery vasorelaxing effects. Whether raloxifene reduces ischemia/reperfusion injury and what mechanisms are involved in the cardioprotective effects were investigated.


METHODS
Infarct size was measured in open-chest dogs following occlusion of the left anterior descending coronary artery for 90 min and subsequent reperfusion for 6 hr. The incidence of ventricular fibrillations during reperfusion period was also observed. Infusion of raloxifene and/or other drugs into the left anterior descending coronary artery was initiated 10 min before coronary occlusion and continued until 1 hr after reperfusion started without an occlusion period.


RESULTS
Infarct size was reduced in the raloxifene (5 micrograms/kg/min) group compared with the control group (6.8 +/- 4.2% vs 40.9 +/- 3.9% of the area at risk, p < 0.01). Either NG-nitro-L-arginine methyl ester, the inhibitor of NO synthase (infarct size: 22.8 +/- 5.4%, p < 0.05 vs raloxifene or the control) or charbdotoxin, the blocker of KCa channels (infarct size: 23.5 +/- 5.1%, p < 0.05 vs raloxifene or the control), partially attenuated the infarct size-limiting effect, and combination of both agents completely abolished the effect (infarct size: 37.7 +/- 5.8%). The incidence of ventricular fibrillations was also less in the raloxifene group than in the control group(11% vs 44%, p < 0.05).


CONCLUSIONS
Raloxifene reduces myocardial infarct size and the incidence of ventricular fibrillations by NO- and the opening of KCa channels-dependent mechanisms in canine hearts.
Ogita
Hisakazu
H
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Yamada-oak 2-2, Suita, Osaka 565-0871.
Node
Koichi
K
Asanuma
Hiroshi
H
Sanada
Shoji
S
Takashima
Seiji
S
Asakura
Masanori
M
Kitakaze
Masafumi
M
Hori
Masatsugu
M
D000818:Animals; D004285:Dogs; D004958:Estradiol / Q000494:pharmacology; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D009206:Myocardium / Q000473:pathology*; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*
D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride; D004958:Estradiol