Chronically elevated bilirubin protects from cardiac reperfusion injury in the male Gunn rat

Abstract

These data reveal life-long hyperbilirubinaemia induces age-dependent hypocontractility in male Gunn rats, and improved stress resistance. In addition, bilirubin exerts sex-independent effects on vascular structure, myocardial function and ischaemic tolerance, the latter likely mediated via bilirubin's antioxidant properties.

Bilirubin protects the ageing heart

“…The anti-inflammatory role of bilirubin in cellular aging has been demonstrated in Gunn rats as they have lower serum levels of proinflammatory cytokines including TNFα, IL1β and IL18 as well as decreased expression of senescence markers. These anti-inflammatory effects of hyperbilirubinemia might have contributed to the reduced levels of oxidation and improvement cardiac function observed after ischemia-reperfusion injury in aged male rat hearts in the present study 1 .…”

“…These effects of bilirubin on cardiac function were observed in both aged males and females suggesting that this is not a sex-dependent phenomenon. More importantly, plasma hyperbilirubinemia protected hearts in both males and females from ischemia-reperfusion injury 1, 4 . In the aged male hearts, this protection was evident in the form of reduced infarct size and improvement in cardiac performance following ischemia-reperfusion injury 1 .…”

“…, examined the effects of hyperbilirubinemia on the aging male heart under basal conditions and after ischemic injury 1 . Heart disease is a significant problem for the aging population in general and males in particular.…”

“…The Bulmer group has used this model to determine the effect of hyperbilirubinemia on cardiac function in aged males and females 1, 4 . Plasma hyperbilirubinemia in the Gunn rat resulted in negative inotropic effect on the heart in the form of reductions in the rate of aortic pressure development, mean aortic velocity, aortic volume time integral pressure gradient in association with significant aortic dilatation 1, 4 . These effects of bilirubin on cardiac function were observed in both aged males and females suggesting that this is not a sex-dependent phenomenon.…”

Current matters of the heart

“…Bilirubin had until recently been considered to be a cytotoxic waste product. Very surprisingly at first, recent studies have shown bilirubin to have cardioprotective effects, potentially exerted through its antioxidant, anti‐inflammatory, vasodilatory, antiapoptotic and antiproliferative properties …”