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Int J Cardiol. 2016 Jan 1;202:27-33. doi: 10.1016/j.ijcard.2015.08.192. Epub 2015 Sep 1.

Pre- or post-ischemic bilirubin ditaurate treatment reduces oxidative tissue damage and improves cardiac function.

Author information

1
Heart Foundation Research Centre, Griffith Health Institute, Griffith University, Gold Coast, Australia.
2
Heart Foundation Research Centre, Griffith Health Institute, Griffith University, Gold Coast, Australia; Department of Nutritional Science, University of Vienna, Vienna, Austria.
3
Heart Foundation Research Centre, Griffith Health Institute, Griffith University, Gold Coast, Australia. Electronic address: a.bulmer@griffith.edu.au.

Abstract

BACKGROUND:

Unconjugated bilirubin (UCB), an endogenous antioxidant, may protect the heart against ischemia-reperfusion (I-R) injury. However, the 'cardioprotective' potential of bilirubin therapy remains unclear. We tested whether pre- or post-ischemic treatment of ex vivo perfused hearts with bilirubin ditaurate (BRT) improves post-ischemic functional outcomes and myocardial oxidative damage.

METHODS:

Isolated Langendorff perfused hearts (male, Wistar rats) were treated with 50 μM BRT for 30 min before (Pre) or after (Post) 30 min of zero-flow ischemia. Functional outcomes were monitored, with myocardial damage estimated from creatine kinase efflux, infarct size, and left ventricular lipid/protein oxidation assessed by measuring malondialdehyde and protein carbonyls. Ischemia induced contractile dysfunction and cellular injury, with both BRT treatments improving I-R outcomes.

RESULTS:

Final post-ischemic recoveries for left ventricular diastolic/developed pressures were significantly enhanced in treated groups: end-diastolic pressure (Control, 78±14, Pre, 51±15*, Post, 51±13 mm Hg*); left ventricular developed pressure, (LVDP; Control 44±15, Pre, 71±19*, Post, 84±13 mm Hg*). Myocardial injury/infarction (MI) was also significantly reduced with BRT treatment: post-ischemic creatine kinase efflux (Control, 1.24±0.41, Pre, 0.86±0.31*, Post, 0.51±0.29 U/g/mL*; infarct size, Control, 67±17, Pre, 39±15*, Post, 22±11%*). These changes were accompanied by significantly reduced malondialdehyde and protein carbonyl content in Pre and Post treated hearts (*P<0.05 vs. Control).

CONCLUSIONS:

These data collectively reveal significant cardioprotection upon BRT treatment, with post-treatment being particularly effective. Significant reductions in infarct size and lipid and protein oxidation indicate a mechanism related to protection from oxidative damage and indicate the potential utility of this molecule as a post-MI treatment.

KEYWORDS:

Antioxidant; Gilbert's syndrome; Heme oxygenase; Myocardial ischemia–reperfusion; Oxidative stress

PMID:
26386915
DOI:
10.1016/j.ijcard.2015.08.192
[Indexed for MEDLINE]

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