Myocardial protection by interferon-γ late preconditioning during cardiopulmonary bypass-associated myocardial ischemia-reperfusion in pigs

Abstract

The impact of interferon-γ (IFN-γ) late preconditioning on myocardial ischemia-reperfusion injury during cardiopulmonary bypass (CPB) and the underlying mechanism were investigated. Using a porcine model of myocardial ischemia-reperfusion injury during CPB with a 60-min aorta cross-clamp, 20pigs (15±0.5kg) were treated randomly with either a 1-ml (20,000IU/kg) IFN-γ injection (IFN-γ group; n=10) or saline solution (control group; n=10) 24h prior to CPB. Heart rate, blood pressure, left ventricular end-systolic pressure (LVESP), left ventricular end-diastolic pressure (LVEDP), creatine kinase isoenzyme-MB (CK-MB), and cardiac troponin I (cTnI) were measured before CPB, before aortic clamping, and at post-reperfusion intervals of 10, 30, 60 and 120min. Heat shock protein 70 (HSP70), Mn-superoxide dismutase (Mn-SOD) and inducible nitric oxide synthase (iNOS) were measured by immunohistochemical staining in pre-CPB myocardial tissues. Myocardial cell apoptosis TUNEL measurement was assessed in samples obtained 60min following reperfusion. Both groups exhibited no statistical differences in age, weight, gender and preoperative cardiac function, and worsened left ventricular function, and hemodynamic index reductions, and significant cTnI and CK-MB leakage was observed 10 and 30min after reperfusion. At 10, 30 and 60min following reperfusion, ventricular function and leakage of the IFN-γ group were significantly improved, and expression of HSP70, iNOS and Mn-SOD increased and myocardial cell apoptosis decreased. IFN-γ late preconditioning exhibited preventative effects on myocardial tissues in pigs during CPB surgery, likely due to increased HSP70, Mn-SOD and iNOS expression.