High basal level of autophagy in high-altitude residents attenuates myocardial ischemia–reperfusion injury

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.