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ORIGINAL RESEARCH ARTICLE

Hyperbaric Oxygen Preconditioning Alleviates Myocardial Ischemic Injury in Rats

Cuihong Han^*,,1, Li Lin^,1, Weidong Zhang^*, Li Zhang^*, Shijun Lv^*, Qiang Sun, Hengyi Tao, John H. Zhang and Xuejun Sun^,2

^* Department of Pathology, Weifang Medical College, Shandong 261042, People’s Republic of China; Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, People’s Republic of China; Department of Physiology, Second Military Medical University, Shanghai 200433, People’s Republic of China; and Department of Neurosurgery, Loma Linda University, Loma Linda, California 92354

To whom requests for reprints should be addressed at ² Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, People’s Republic of China. E-mail address: sunxjk{at}hotmail.com

It has been shown that after ischemia-reperfusion, application of hyperbaric oxygen (HBO) reduces cardiac injury. In this study we tested the hypothesis that HBO preconditioning reduces injury to the ischemic myocardium. One hundred and eight adult male Sprague-Dawley rats (250–280 g) were randomly divided into four groups: normoxia + sham surgery (CS), normoxia + permanent occlusion of the left anterior descending (LAD) coronary artery (CMI), HBO preconditioning + sham surgery (HS), and HBO preconditioning + permanent LAD occlusion (HMI). Rats receiving HBO preconditioning were intermittently exposed to 100% O₂ at 2.5 atmosphere absolute (ATA) for 60 min, twice daily for 2 days followed by 12 hrs of recovery in room air prior to the myocardial ischemic insult induced by LAD ligation. Rats in the normoxia group were time-matched with the HBO group and maintained under normoxic conditions prior to LAD occlusion. At 3 and 7 days after LAD occlusion, heart function parameters were measured by inserting a catheter into the left ventricle, infarct size was calculated using the method of TTC staining, myocardial capillary density was determined by immunohistochemical staining with a monoclonal anti-CD₃₁/PECAM-1 antibody, and VEGF protein level was determined by Western blot analysis. At 3 days after LAD ligation, the infarct size of the HMI group was significantly smaller than that of the CMI group (26 ± 2.5% vs. 38 ± 3%, P < 0.05). The heart function parameters including left ventricular systolic pressure (LVSP), +dP/dt_max and –dP/dt_max were significantly improved in the HMI group compared to the CMI group at 3 and 7 days after LAD occlusion. Capillary density and VEGF protein levels were significantly increased in the ischemic myocardium pre-exposed to HBO. We conclude that HBO preconditioning alleviates myocardial ischemia in rat model.

Key Words: myocardial infarction • angiogenesis • hyperbaric oxygen preconditioning • VEGF