Pretreatment with fosinopril or valsartan reduces myocardial no-reflow after acute myocardial infarction and reperfusion.

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Zhao JL, Yang YJ, You SJ, Jing ZC, Wu YJ, Cheng JL, Gao RL

Pretreatment with fosinopril or valsartan reduces myocardial no-reflow after acute myocardial infarction and reperfusion.

Coron Artery Dis. 2006 Aug;17(5):463-9.

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16845255 [ View in PubMed

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Abstract

BACKGROUND: Both fosinopril and valsartan are effective in protecting endothelial function. We hypothesized that they may also reduce myocardial no-reflow. In addition, suppression of adenosine triphosphate-sensitive K (KATP) channel opening is an important mechanism for myocardial no-reflow. Therefore, this study sought to assess the effect of fosinopril and valsartan on myocardial no-reflow and explore the possible mechanism. METHODS: Coronary ligation area and the area of no-reflow were determined with both myocardial contrast echocardiography in vivo and pathological means in 56 mini-swine randomized into seven study groups: eight in control, eight in fosinopril-pretreated (1 mg/kg/day) for 3 days, eight in fosinopril and glibenclamide (KATP channel blocker)-pretreated, eight in valsartan-pretreated (2 mg/kg/day) for 3 days, eight in valsartan and glibenclamide-pretreated, eight in glibenclamide-treated and eight in sham-operated. An acute myocardial infarction and reperfusion model was created with a 3-h occlusion of the coronary artery followed by a 2-h reperfusion. The levels of KATP channel proteins (SUR2, Kir6.1, and Kir6.2) in the reflow and no-reflow myocardium were quantified by Western blotting. RESULTS: Compared with the control group, both fosinopril and valsartan significantly improved ventricular function, decreased area of no-reflow (myocardial contrast echocardiography: from 78.5+/-4.5 to 24.5+/-2.7 and 24.3+/-3.6%, pathological means: from 82.3+/-1.9 to 25.2+/-3.2 and 24.9+/-4.4% of ligation area, respectively; all P<0.01), reduced necrosis size from 98.5+/-1.3 to 88.9+/-3.6 and 89.1+/-3.1% of ligation area, respectively (both P<0.05). They also increased the levels of SUR2 and Kir6.2 (P<0.01), but had no effect on the level of Kir6.1 (P>0.05). A combination of fosinopril or valsartan with glibenclamide significantly increased area of no-reflow (P<0.05) and decreased the levels of SUR2 and Kir6.2 (P<0.01). CONCLUSIONS: Pretreatment with fosinopril or valsartan can reduce myocardial no-reflow. This beneficial effect is due to activation of the KATP channel.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
ATP	ATP-binding cassette sub-family C member 9	Protein	Humans	Unknown	Not Available	Details
Glyburide	ATP-binding cassette sub-family C member 9	Protein	Humans	Unknown	Modulator	Details