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Hao Zhang, Ding-xu Gong, Yu-jian Zhang, Shou-jun Li, Shengshou Hu, Effect of mitochondrial aldehyde dehydrogenase-2 genotype on cardioprotection in patients with congenital heart disease, European Heart Journal, Volume 33, Issue 13, July 2012, Pages 1606–1614, https://doi.org/10.1093/eurheartj/ehs061
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Abstract
About 40% of East Asians carry an aldehyde dehydrogenase-2*2 (ALDH2*2) allele, and the influence of the ALDH2*2 allele on human cardioprotection has not been studied. This study was designed to evaluate the effect of ALDH2*2 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 ALDH2*2 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 ALDH2*2 carriers and non-carriers.
Cyanosis inhibited ALDH2 activity and led to aldehyde accumulation in ALDH2*2 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, ALDH2*2 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.
- alleles
- myocardium
- open heart surgery
- oxidative stress
- phenotype
- cardiopulmonary bypass
- tetralogy of fallot
- cyanosis
- mitochondria
- congenital heart disease
- heart arrest, induced
- cyanotic congenital heart disease
- glutathione
- aldehydes
- genotype
- intensive care unit
- oxidoreductase
- surgical procedures, operative
- troponin i
- inotropic agents
- congenital heart disease, acyanotic
- genotype determination
- asian
- right auricular appendage