Abstract 9139: Mitochondrial Aldehyde Dehydrogenase 2*2 Allele Carriers Possess Better Cardioprotection Results After Cardioplegic Arrest During Open-Heart Surgery
Introduction: Previous rodent studies indicated aldehyde dehydrogenase-2 (ALDH2) activation conferred cardioprotection. About 40% East Asians carry an ALDH2*2 allele to result in a reduced ALDH2 activity. The influence of ALDH2*2 on human cardioprotection after cardioplegia has not been studied, and we hypothesized that ALDH2*2 allele could have an effect on it.
Methods: A prospective cohort of East Asians with a diagnosis of Tetralogy of Fallot (n=80) undergoing elective surgical repair were genotyped. All subjects followed the same operation and ICU protocol. Myocardium samples were dissected after cardioplegic arrest and detailed clinical information were collected. Myocardium ALDH2 activity, 4-hydroxy-2-nonenal (4-HNE) adducts and glutathione (GSH) levels, and expressions of ALDH2 and activating transcription factor-4 (ATF4), a key transcriptional regulator for GSH formation, were determined by spectrophotography, ELISA, and western blotting respectively. All the experimental and clinical results were compared between ALDH2*2 carriers and non-carriers.
Results: ALDH2*2 allele presented in 38.75% of the patients. Myocardium ALDH2 enzyme activity difference among ALDH2*2 carriers and non-carriers disappeared during cardioplegia. ALDH2*2 carriers expressed less ALDH2 and more ATF4, and they got lower 4-HNE adducts levels and higher GSH levels. A lower postoperative inotropic score and troponin I level, and shorter length of hospital stay were observed in ALDH2*2 carriers (Table).
Conclusions: In order to antagonize oxidative stress, ALDH2*2 carriers developed a compensatory larger myocardium GSH pool through ATF4 activation. When ALDH2 activity was impaired during cardioplegia, this larger GSH pool leaded to unexpectedly better cardioprotection results on ALDH2*2 carriers. ALDH2 genotype might be served as a genetic predictor for cardioprotection, and new cardioprotective strategies for ALDH2*2 non- carriers should be developed.
- © 2011 by American Heart Association, Inc.