• Yijie Hu, Qi Sun, Zhiping Li, Jianming Chen, Cheng Shen, Yi Song, and Qianjin Zhong.
• Department of Cardiovascular Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
• J. Thorac. Cardiovasc. Surg.. 2014 Oct 1;148(4):1674-80.

ObjectiveHypoxia can induce autophagy, which plays an important role in cardioprotection. The present study tested the hypothesis that patients with congenital heart disease living at a high altitude could resist ischemia-reperfusion injury better than those at a low altitude, through elevated basal autophagy by chronic hypoxia.MethodsTwelve Tibetan patients residing at a high altitude of >3000 m and 12 Han patients residing at a low altitude of <500 m with simple atrial or ventricular septal defects were prospectively recruited. All patients underwent cardiopulmonary bypass, maintaining a flow rate of approximately 2.4 to 2.8 L/min/m2 and mean arterial pressure of ≥40 to 60 mm Hg. Myocardial ischemia-reperfusion injury between the 2 groups was compared using cardiac troponin I, brain natriuretic peptide, hematoxylin eosin staining, and the terminal deoxynucleotidyl transferase dUTP nick end labeling test. Autophagy-related proteins microtubule-associated protein 1 light chain 3 II (LC3II), Beclin1, and lysosomal-associated membrane protein 2 (LAMP2) and their upstream protein BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 (Bnip3) were evaluated with Western blotting.ResultsThe maximal cardiac troponin I concentration and increasing x-fold of brain natriuretic peptide in the high-altitude group were obviously lower than those in the low-altitude group (3.10±0.77 vs 7.10±2.28 ng/mL and 2.51±0.94 vs 14.66±6.83, respectively). The preoperative and postoperative levels of LC3II, LAMP2, and upstream Bnip3 in the high-altitude group were obviously greater. No difference was found in the Beclin1 level between the 2 groups at baseline or ischemia-reperfusion.ConclusionsPatients living at a high altitude with congenital heart disease resisted ischemia-reperfusion injury during cardiac surgery better than those at a low altitude, possibly through elevated basal autophagy induced by chronic hypoxia.Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

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