{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:57:46Z","timestamp":1785419866537,"version":"3.56.0"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,3,14]],"date-time":"2017-03-14T00:00:00Z","timestamp":1489449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["P 21162\u2010B11"],"award-info":[{"award-number":["P 21162\u2010B11"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Bilirubin is associated with reduced risk of cardiovascular disease, as evidenced in conditions of mild hyperbilirubinaemia (Gilbert's Syndrome). Little is known regarding myocardial stress resistance in hyperbilirubinaemic conditions or whether life\u2010long exposure modifies cardiac function, which might contribute to protection from cardiovascular disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Hyperbilirubinaemic rats and littermate controls underwent echocardiography at 3, 6 and 12 months of age, with hearts subsequently assessed for resistance to 30 min of ischaemia. Heart tissue was then collected for assessment of bilirubin content.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>No difference in baseline cardiac function was evident until 6 months onwards, where Gunn rats demonstrated aortic dilatation and reduced peak ejection velocities. Additionally, duration of ventricular ejection increased progressively, indicating a negative inotropic effect of bilirubin <jats:italic>in vivo<\/jats:italic>. <jats:italic>Ex vivo<\/jats:italic> analysis of baseline function revealed reduced left ventricular pressure development (<jats:styled-content style=\"fixed-case\">LVDP<\/jats:styled-content>) and contractility in hyperbilirubinaemic rats. Furthermore, stress resistance was improved in Gunn hearts: post\u2010ischaemic recoveries of <jats:styled-content style=\"fixed-case\">LVDP<\/jats:styled-content> (76 \u00b1 22% vs. 29 \u00b1 17% Control, <jats:italic>P<\/jats:italic> &lt; 0.01) and coronary flow (96 \u00b1 9% vs. 86 \u00b1 16% Control, <jats:italic>P<\/jats:italic> &lt; 0.01) were improved in Gunn hearts, accompanied by reduced infarct area (21 \u00b1 5% vs. 47 \u00b1 15% Control, <jats:italic>P<\/jats:italic> &lt; 0.01), and ventricular malondialdehyde and protein carbonyl content. Expression of myocardial nitric oxide\u2010regulating genes including <jats:italic>Nos1<\/jats:italic> and <jats:italic>Noa1<\/jats:italic> were not significantly different.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data reveal life\u2010long hyperbilirubinaemia induces age\u2010dependent hypocontractility in male Gunn rats, and improved stress resistance. In addition, bilirubin exerts sex\u2010independent effects on vascular structure, myocardial function and ischaemic tolerance, the latter likely mediated via bilirubin's antioxidant properties.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.12858","type":"journal-article","created":{"date-parts":[[2017,2,16]],"date-time":"2017-02-16T17:46:44Z","timestamp":1487267204000},"page":"461-470","source":"Crossref","is-referenced-by-count":24,"title":["Chronically elevated bilirubin protects from cardiac reperfusion injury in the male Gunn rat"],"prefix":"10.1111","volume":"220","author":[{"given":"B.","family":"Bakrania","sequence":"first","affiliation":[{"name":"Heart Foundation Research Centre Menzies Health Institute Queensland Griffith University Gold Coast Qld Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. 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