Hyperbilirubinemia modulates myocardial function, aortic ejection and ischemic stress-resistance in the Gunn rat

Autoren:Bakrania, Bhavisha (Griffith University); Du Toit, Eugene Francois (Griffith University); Ashton, Kevin J (Bond University); Kiessling, Can J (Bond University); Wagner, Karl-Heinz; Headrick, John P (Griffith University); Bulmer, Andrew Cameron (Griffith University)

Mildly elevated circulating unconjugated bilirubin (UCB) is associated with protection against hypertension and ischemic heart disease. We assessed whether endogenously elevated bilirubin in Gunn rats modifies cardiovascular function and resistance to ischemic insult. Hearts were assessed ex vivo (Langendorff perfusion) and in vivo (Millar catheterization, echocardiography), and left ventricular myocardial gene expression was measured via quantitative real time PCR (RT-qPCR). Ex vivo analysis revealed reduced intrinsic contractility in Gunn myocardium (+dP/dt, 1976±622 vs. 2907±334 mmHg/s, P<0.01; -dP/dt, -1435±372 vs. -2234±478, P<0.01), which correlated positively with myocardial [UCB] (P<0.05). In vivo analyses showed no changes in left ventricular contractile parameters and ejection (fractional shortening, ejection fraction). However, Gunn rats exhibited reductions in rate of aortic pressure development (3008±461 vs. 4452±644 mmHg/s,P<0.02), mean aortic velocity (439±64 vs. 644±62 ml/s, P<0.01) and the aortic volume time integral pressure gradient (2.32±0.65 vs. 5.72±0.74 mmHg, P<0.01), in association with significant aortic dilatation (12-24% increase in aortic diameter, P<0.05). Ex vivo Gunn hearts exhibited improved ventricular function after 90 mins of reperfusion, following 35 min ischemia (63±14 vs. 35±12%, P<0.01). These effects were accompanied by increased glutathione peroxidase and reduced superoxide dismutase and phospholamban gene expression in Gunn myocardium (P<0.05). These data collectively indicate that hyperbilirubinemia in Gunn rats: i) reduces intrinsic cardiac contractility, which is compensated for in vivo; ii) induces aortic dilatation that may beneficially influence aortic ejection velocities and pressures; and iii) may improve myocardial stress-resistance in association with beneficial transcriptional changes. These effects may contribute to protection from CVD with elevated bilirubin.

Journaltitel:American Journal of Physiology. Heart and Circulatory Physiology
Peer reviewed:true
Digital Object Identifier (DOI):http://dx.doi.org/10.1152/ajpheart.00001.2014
Bibliographische Notiz:Copyright © 2014, American Journal of Physiology - Heart and Circulatory Physiology.