State Key Laboratory of Cardiovascular Medicine, Fuwai Hospital, National Center for Cardiovascular Disease, Beijing, China.
Eur Heart J. 2012 Jul;33(13):1606-14. doi: 10.1093/eurheartj/ehs061. Epub 2012 Apr 16.
About 40% of East Asians carry an aldehyde dehydrogenase-22 (ALDH22) allele, and the influence of the ALDH22 allele on human cardioprotection has not been studied. This study was designed to evaluate the effect of ALDH22 allele on cardioprotection of patients with congenital heart diseases after open-heart surgery.
The right atrial appendage was harvested before performing cardiopulmonary bypass in cyanotic and acyanotic congenital heart disease groups (n = 20 per group). Tissues were assayed to determine the impact of cyanosis on metabolic remodelling. A prospective cohort of Tetralogy of Fallot (TOF) patients (n = 118) was recruited to investigate the influence of the ALDH22 allele on cardioprotection after surgical repair. Myocardium samples were dissected after cardioplegia. ALDH2 activity, oxidative stress and glutathione (GSH) levels, and activating transcription factor-4 (ATF4) were analysed. After genotyping and grouping, all of the experimental and clinical results were compared between ALDH22 carriers and non-carriers. Cyanosis inhibited ALDH2 activity and led to aldehyde accumulation in ALDH22 carriers. This accumulation in turn increased expression of ATF4 and resulted in larger myocardium GSH pools. The differences in ALDH2 activity and GSH level between carriers and non-carriers disappeared during cardioplegic arrest, and more aldehydes accumulated in the non-carriers. Consequently, ALDH22 carriers showed lower postoperative troponin I, inotrope score, and shorter postoperative length of ICU and hospital stay.
ALDH2*2 carriers with cyanotic congenital heart disease were associated with an induced metabolic remodelling phenotype and a compensatory myocardium GSH pool. When ALDH2 activity was impaired during open-heart surgery, this larger GSH pool could lead to unexpectedly better cardioprotection. This may aid in the prediction of cardioprotection outcomes and identification of individualized cardioprotective strategies.
约 40%的东亚人携带乙醛脱氢酶-22（ALDH22）等位基因，而该等位基因对人类心脏保护的影响尚未得到研究。本研究旨在评估 ALDH2*2 等位基因对体外循环下心内直视手术患者心脏保护的影响。
在发绀和非发绀先天性心脏病组（每组 20 例）进行体外循环前，采集右心耳组织，以确定发绀对代谢重塑的影响。前瞻性招募法洛四联症（TOF）患者（n=118）队列，以研究 ALDH22 等位基因对手术修复后心脏保护的影响。心脏停搏后剖开心肌组织，分析 ALDH2 活性、氧化应激和谷胱甘肽（GSH）水平及激活转录因子 4（ATF4）。基因分型和分组后，比较 ALDH22 携带者和非携带者之间的所有实验和临床结果。发绀抑制 ALDH2 活性并导致 ALDH22 携带者醛的积累。这种积累继而增加 ATF4 的表达，并导致更大的心肌 GSH 池。携带者和非携带者之间的 ALDH2 活性和 GSH 水平的差异在心脏停搏期间消失，并且非携带者中积累了更多的醛。因此，ALDH22 携带者的术后肌钙蛋白 I、正性肌力药评分和术后 ICU 和住院时间较短。
发绀性先天性心脏病患者的 ALDH2*2 携带者与诱导的代谢重塑表型和代偿性心肌 GSH 池相关。当体外循环下心内直视手术期间 ALDH2 活性受损时，这种更大的 GSH 池可能导致出乎意料的更好的心脏保护。这可能有助于预测心脏保护结果并确定个体化的心脏保护策略。
