Aldehyde dehydrogenase-2 activation during cardioplegic arrest enhances the cardioprotection against myocardial ischemia-reperfusion injury.
Cardiovasc Toxicol
; 12(4): 350-8, 2012 Dec.
Article
en En
| MEDLINE
| ID: mdl-22814936
Ischemia/reperfusion damage is common during open-heart surgery. Activation of aldehyde dehydrogenase-2 can significantly reduce ischemia/reperfusion damage. We hypothesized that adding aldehyde dehydrogenase-2 agonist to regular cardioplegia solution would further ameliorate ischemia/reperfusion damage. Alda-1 was used as an aldehyde dehydrogenase-2 agonist. Cardioprotection by histidine-tryptophan-ketoglutarate solution with and without Alda-1 was compared using an ex vivo perfused rat heart model of ischemia/reperfusion. Three groups of ex vivo rat hearts endured different treatments with variant ischemia or an ischemia/reperfusion time course: sham, no ischemia/reperfusion; histidine-tryptophan-ketoglutarate; and histidine-tryptophan-ketoglutarate plus Alda-1. Aldehyde dehydrogenase-2 expressions and activities, oxidative parameters (including 4-hydroxy-2-nonenal-His adducts, malondialdehyde levels, and glutathione/oxidized glutathione ratios), myocardial protein carbonyl levels, coronary effluents creatine kinase isoenzyme MB levels, and heart function parameters were measured and compared. Alda-1 significantly elevated myocardium aldehyde dehydrogenase-2 activity (P < .01). Increased aldehyde dehydrogenase-2 activity in turn attenuated ischemia/reperfusion-induced elevation in cardiac aldehydes, creatine kinase isoenzyme MB leakage, and protein carbonyl formation (P < .01). The Alda-1 group also obtained higher glutathione/oxidized glutathione ratios (P < .01). Aldehyde dehydrogenase-2 activation alleviated ischemia/reperfusion-induced cardiomyocyte contractile function impairment as evidenced by improved maximal velocity of pressure development and decline, left ventricular developed pressure, and heart rate (P < .01). Alda-1 supplementation can significantly improve the cardioprotection effect of cardioplegia solution, possibly through activation of aldehyde dehydrogenase-2, to remove toxic aldehydes. This may aid in the identification of novel cardioplegia solutions.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cardiotónicos
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Daño por Reperfusión Miocárdica
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Proteínas Mitocondriales
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Aldehído Deshidrogenasa
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Paro Cardíaco
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Paro Cardíaco Inducido
Límite:
Animals
Idioma:
En
Revista:
Cardiovasc Toxicol
Asunto de la revista:
ANGIOLOGIA
/
CARDIOLOGIA
/
TOXICOLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos