title: Aldehyde dehydrogenase-2 activation during cardioplegic arrest enhances the cardioprotection against myocardial ischemia-reperfusion injury.
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.
authors: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors: Dingxu
authors: D
authors: Gong
authors: Yujian
authors: Y
authors: Zhang
authors: Hao
authors: H
authors: Zhang
authors: Haiyong
authors: H
authors: Gu
authors: Qin
authors: Q
authors: Jiang
authors: Shengshou
authors: S
authors: Hu
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism / Q000502:physiology*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use; D052117:Benzodioxoles / Q000494:pharmacology / Q000627:therapeutic use; D002314:Cardioplegic Solutions / Q000494:pharmacology / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000819:agonists / Q000627:therapeutic use*; D004789:Enzyme Activation / Q000502:physiology; D006323:Heart Arrest / Q000201:enzymology* / Q000517:prevention & control; D006324:Heart Arrest, Induced / Q000379:methods*; D008297:Male; D024101:Mitochondrial Proteins / Q000819:agonists / Q000378:metabolism / Q000502:physiology*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D001549:Benzamides; D052117:Benzodioxoles; D002314:Cardioplegic Solutions; D002316:Cardiotonic Agents; D024101:Mitochondrial Proteins; C531525:N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C505112:Aldh2 protein, rat