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- Title
Aldehyde Dehydrogenase-2 Activation during Cardioplegic Arrest Enhances the Cardioprotection against Myocardial Ischemia-Reperfusion Injury.
- Authors
Gong, Dingxu; Zhang, Yujian; Zhang, Hao; Gu, Haiyong; Jiang, Qin; Hu, Shengshou
- Abstract
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.
- Subjects
ALDEHYDE dehydrogenase; CARDIOPLEGIC solutions; CORONARY disease; REPERFUSION injury; CARDIAC surgery; HISTIDINE; TRYPTOPHAN
- Publication
Cardiovascular Toxicology, 2012, Vol 12, Issue 4, p350
- ISSN
1530-7905
- Publication type
Article
- DOI
10.1007/s12012-012-9179-6