Chronically elevated bilirubin protects from cardiac reperfusion injury in the male Gunn rat
Author(s)
Bakrania, B
Du Toit, EF
Ashton, KJ
Wagner, K-H
Headrick, JP
Bulmer, AC
Year published
2017
Metadata
Show full item recordAbstract
Aims: Bilirubin is associated with reduced risk of cardiovascular disease,as evidenced in conditions of mild hyperbilirubinaemia (Gilbert’s Syn-drome). Little is known regarding myocardial stress resistance in hyper-bilirubinaemic conditions or whether life-long exposure modifies cardiacfunction, which might contribute to protection from cardiovascular dis-ease.Methods: Hyperbilirubinaemic rats and littermate controls underwentechocardiography at 3, 6 and 12 months of age, with hearts subsequentlyassessed for resistance to 30 min of ischaemia. Hear t tissue was then col-lected for assessment of bilirubin content.Results: No ...
View more >Aims: Bilirubin is associated with reduced risk of cardiovascular disease,as evidenced in conditions of mild hyperbilirubinaemia (Gilbert’s Syn-drome). Little is known regarding myocardial stress resistance in hyper-bilirubinaemic conditions or whether life-long exposure modifies cardiacfunction, which might contribute to protection from cardiovascular dis-ease.Methods: Hyperbilirubinaemic rats and littermate controls underwentechocardiography at 3, 6 and 12 months of age, with hearts subsequentlyassessed for resistance to 30 min of ischaemia. Hear t tissue was then col-lected for assessment of bilirubin content.Results: No difference in baseline cardiac function was evident until6 months onwards, where Gunn rats demonstrated aortic dilatation andreduced peak ejection velocities. Additionally, duration of ventricular ejec-tion increased progressively, indicating a negative inotropic effect of biliru-bin in v ivo. Ex vivo analysis of baseline function revealed reduced leftventricular pressure development (LVDP) and contractility in hyperbiliru-binaemic rats. Furthermore, stress resistance was improved in Gunn hearts:post-ischaemic recoveries of LVDP (76 22% vs. 29 17% Control,P < 0.01) and coronary flow (96 9% vs. 86 16% Control, P < 0.01)were improved in Gunn hearts, accompanied by reduced infarct area(21 5% vs. 47 15% Control, P < 0.01), and ventricular malondialde-hyde and protein carbonyl content. Expression of myocardial nitric oxide-regulating genes including Nos1 and Noa1 were not significantly different.Conclusions: These data reveal life-long hyperbilirubinaemia induces age-dependent hypocontractility in male Gunn rats, and improved stress resis-tance. In addition, bilirubi n exerts sex-independent effects on vascularstructure, myocardial function and ischaemic tolerance, the latter likelymediated via bilirubin’s antioxidant properties.Keywords bilirubin, cardiovascular disease, Gilbert’s syndrome, hemeoxygenase-1, ischaemia–reperfusion injury.
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View more >Aims: Bilirubin is associated with reduced risk of cardiovascular disease,as evidenced in conditions of mild hyperbilirubinaemia (Gilbert’s Syn-drome). Little is known regarding myocardial stress resistance in hyper-bilirubinaemic conditions or whether life-long exposure modifies cardiacfunction, which might contribute to protection from cardiovascular dis-ease.Methods: Hyperbilirubinaemic rats and littermate controls underwentechocardiography at 3, 6 and 12 months of age, with hearts subsequentlyassessed for resistance to 30 min of ischaemia. Hear t tissue was then col-lected for assessment of bilirubin content.Results: No difference in baseline cardiac function was evident until6 months onwards, where Gunn rats demonstrated aortic dilatation andreduced peak ejection velocities. Additionally, duration of ventricular ejec-tion increased progressively, indicating a negative inotropic effect of biliru-bin in v ivo. Ex vivo analysis of baseline function revealed reduced leftventricular pressure development (LVDP) and contractility in hyperbiliru-binaemic rats. Furthermore, stress resistance was improved in Gunn hearts:post-ischaemic recoveries of LVDP (76 22% vs. 29 17% Control,P < 0.01) and coronary flow (96 9% vs. 86 16% Control, P < 0.01)were improved in Gunn hearts, accompanied by reduced infarct area(21 5% vs. 47 15% Control, P < 0.01), and ventricular malondialde-hyde and protein carbonyl content. Expression of myocardial nitric oxide-regulating genes including Nos1 and Noa1 were not significantly different.Conclusions: These data reveal life-long hyperbilirubinaemia induces age-dependent hypocontractility in male Gunn rats, and improved stress resis-tance. In addition, bilirubi n exerts sex-independent effects on vascularstructure, myocardial function and ischaemic tolerance, the latter likelymediated via bilirubin’s antioxidant properties.Keywords bilirubin, cardiovascular disease, Gilbert’s syndrome, hemeoxygenase-1, ischaemia–reperfusion injury.
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Journal Title
Acta Physiologica
Volume
220
Issue
4
Subject
Sports science and exercise
Medical physiology
Medical physiology not elsewhere classified