Ozone preconditioning protects rabbit heart against global ischemia-reperfusion injury in vitro by up-regulating HIF-1α.

Abstract

Myocardial ischemia-reperfusion injury (MIRI) is a major factor that leads to cardiac dysfunction in cardiovascular surgery during extracorporeal circulation. Recent studies have found that ozone (O3) has protective effect on MIRI caused by the anterior descending branch of the ligated left coronary artery. However, whether O3 preconditioning has the same protective effect on global MIRI and the mechanism underlying this clinical treatment remains elusive. Here, we hypothesized that O3 preconditioning (O3P) could protect rabbit heart against global MIRI in vitro by up-regulating HIF-1α. Rabbits were treated intraperitoneally with O2/O3 mixture with different concentrations and then injected with YC-1 (inhibitor of HIF-1α) before the establishment of the global MIRI model using the Langendorff isolated heart perfusion apparatus. We investigated the effects of O3 preconditioning on cardiac systolic function, myocardial infarction, inflammatory response, mitochondrial function, myocardial pathological changes and arrhythmias. We found that the heart with O3 preconditioning significantly increased HR, LVDP and IL-10 expression, and decreased IL-6 expression, CK-MB, cTnT and cTnI concentration, myocardial infarction area, myocardial pathological injury and the occurrence of ventricular tachycardia and ventricular fibrillation. Meanwhile, the level of HIF-1α was significantly increased. However, after treatment of specific inhibitor of HIF-1α, the protective effect of O3 preconditioning was reversed completely. Our data indicates that O3 preconditioning has protective effect on MIRI and this protective effect is positively associated with dosage of O3. Energy metabolism disorder is the initial stage of MIRI and up-regulation of HIF-1α plays an important role in reducing mitochondrial dysfunction.