Effects of Endogenously and Exogenously Elevated Bilirubin on Myocardial Ischaemia Reperfusion Injury

Abstract

Cardiovascular disease is the world's greatest killer; additional therapies for targeted prevention/treatment are clearly required. Whether elevated endogenous or exogenous bilirubin attenuates cardiac ischaemia reperfusion injury is currently unknown. Echocardiography did not reveal significant differences (P<0.05) in cardiac structural measures in hyperbilirubinemic Gunn rats, however, showed reduced stroke volume (W‐T, 132 ± 29.2 μL, Gunn, 101 ± 12.8 μL, P=0.049) and peak aortic blood flow velocity (W‐T, 1225 ± 115 mm/s, Gunn, 712 ± 13.9 mm/s, P<0.01) leaving the left ventricle in Gunn rats, which could indicate that bilirubin reduces contractility of the heart. Langendorff perfused Gunn and bilirubin pretreated wild‐type hearts recovered moreso after an ischemic insult versus control hearts. Recovery was most pronounced at 90 minutes of reperfusion (W‐T, 38.5 ± 9.1 %, Gunn, 58.3 ± 11.3 %, P=0.04; Control, 33.5 ± 12.5, Pretreated, 56.3 ± 12.3 %, P=0.036). Tissue unconjugated bilirubin correlated positively with percent recovery in left ventricular developed pressure after ischaemia (r=0.69, P<0.01). These data suggest that the Gunn phenotype (analogous to Gilbert's syndrome in humans) or bilirubin ditaurate pretreatment induces cardioprotection by 1) reducing cardiac contractility at rest and/or 2) protecting from free radical mediated damage during ischaemia reperfusion.