{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T20:38:25Z","timestamp":1776976705973,"version":"3.51.4"},"reference-count":40,"publisher":"American Physiological Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2014,10,15]]},"abstract":"<jats:p>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 and echocardiography), and left ventricular myocardial gene expression was measured via quantitative real-time PCR. Ex vivo analysis revealed reduced intrinsic contractility in the Gunn myocardium (+dP\/d t: 1,976 \u00b1 622 vs. 2,907 \u00b1 334 mmHg\/s, P &lt; 0.01; \u2212dP\/d t: \u22121,435 \u00b1 372 vs. \u22122,234 \u00b1 478 mmHg\/s, P &lt; 0.01), which correlated positively with myocardial UCB concentration ( P &lt; 0.05). In vivo analyses showed no changes in left ventricular contractile parameters and ejection (fractional shortening and ejection fraction). However, Gunn rats exhibited reductions in the rate of aortic pressure development (3,008 \u00b1 461 vs. 4,452 \u00b1 644 mmHg\/s, P &lt; 0.02), mean aortic velocity (439 \u00b1 64 vs. 644 \u00b1 62 mm\/s, P &lt; 0.01), and aortic volume time integral pressure gradient (2.32 \u00b1 0.65 vs. 5.72 \u00b1 0.74 mmHg, P &lt; 0.01), in association with significant aortic dilatation (12\u201324% increase in aortic diameter, P &lt; 0.05). Ex vivo Gunn hearts exhibited improved ventricular function after 35 min of ischemia and 90 min of reperfusion (63 \u00b1 14 vs. 35 \u00b1 12%, P &lt; 0.01). These effects were accompanied by increased glutathione peroxidase and reduced superoxide dismutase and phospholamban gene expression in Gunn rat myocardium ( P &lt; 0.05). These data collectively indicate that hyperbilirubinemia in Gunn rats 1) reduces intrinsic cardiac contractility, which is compensated for in vivo; 2) induces aortic dilatation, which may beneficially influence aortic ejection velocities and pressures; and 3) may improve myocardial stress resistance in association with beneficial transcriptional changes. These effects may contribute to protection from cardiovascular disease with elevated bilirubin.<\/jats:p>","DOI":"10.1152\/ajpheart.00001.2014","type":"journal-article","created":{"date-parts":[[2014,8,16]],"date-time":"2014-08-16T01:35:34Z","timestamp":1408152934000},"page":"H1142-H1149","source":"Crossref","is-referenced-by-count":24,"title":["Hyperbilirubinemia modulates myocardial function, aortic ejection, and ischemic stress resistance in the Gunn rat"],"prefix":"10.1152","volume":"307","author":[{"given":"Bhavisha","family":"Bakrania","sequence":"first","affiliation":[{"name":"Heart Foundation Research Centre, Griffith Health Institute, Griffith University, Gold Coast, Queensland, Australia;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugene F.","family":"Du Toit","sequence":"additional","affiliation":[{"name":"Heart Foundation Research Centre, Griffith Health Institute, Griffith University, Gold Coast, Queensland, 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