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[Amelioration of ischemia- and reperfusion-induced myocardial injury by the selective estrogen receptor modulator, raloxifene, in the canine heart].

Abstract：

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.

journal_name

J Cardiol

journal_title

Journal of cardiology

authors

Ogita H,Node K,Asanuma H,Sanada S,Takashima S,Asakura M,Kitakaze M,Hori M

subject

Has Abstract

pub_date

2002-01-01 00:00:00

pages

55-6

issue

eissn

0914-5087

issn

1876-4738

journal_volume

pub_type

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[Amelioration of ischemia- and reperfusion-induced myocardial injury by the selective estrogen receptor modulator, raloxifene, in the canine heart].