Pre- or post-ischemic bilirubin ditaurate treatment reduces oxidative tissue damage and improves cardiac function

Background: Unconjugated bilirubin (UCB), an endogenous antioxidant, may protect the heart against ischemia-reperfusion (I-R) injury. However, the 'cardioprotective' potential of bilirubin therapy remains unclear. We tested whether pre- or post-ischemic treatment of ex vivo perfused hearts with bilirubin ditaurate (BRT) improves post-ischemic functional outcomes and myocardial oxidative damage. Methods: Isolated Langendorff perfused hearts (male, Wistar rats) were treated with 50 mu M BRT for 30 min before (Pre) or after (Post) 30 min of zero-flow ischemia. Functional outcomes were monitored, with myocardial damage estimated from creatine kinase efflux, infarct size, and left ventricular lipid/protein oxidation assessed by measuring malondialdehyde and protein carbonyls. Ischemia induced contractile dysfunction and cellular injury, with both BRT treatments improving I-R outcomes. Results: Final post-ischemic recoveries for left ventricular diastolic/developed pressures were significantly enhanced in treated groups: end-diastolic pressure (Control, 78 +/- 14, Pre, 51 +/- 15*, Post, 51 +/- 13 mm Hg*); left ventricular developed pressure, (LVDP; Control 44 +/- 15, Pre, 71 +/- 19*, Post, 84 +/- 13 mm Hg*). Myocardial injury/infarction (MI) was also significantly reduced with BRT treatment: post-ischemic creatine kinase efflux (Control, 1.24 +/- 0.41, Pre, 0.86 +/- 0.31*, Post, 0.51 +/- 0.29 U/g/mL*; infarct size, Control, 67 +/- 17, Pre, 39 +/- 15*, Post, 22 +/- 11%*). These changes were accompanied by significantly reduced malondialdehyde and protein carbonyl content in Pre and Post treated hearts (*P < 0.05 vs. Control). Conclusions: These data collectively reveal significant cardioprotection upon BRT treatment, with post-treatment being particularly effective. Significant reductions in infarct size and lipid and protein oxidation indicate a mechanism related to protection from oxidative damage and indicate the potential utility of this molecule as a post-MI treatment. (C) 2015 Elsevier Ireland Ltd. All rights reserved.