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 μM 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.