Bhavisha Bakrania1, Eugene F Du Toit1, Karl-Heinz Wagner2, John P Headrick1, Andrew C Bulmer3. 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.
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.
Authors: Bhavisha A Bakrania; Frank T Spradley; Simon C Satchell; David E Stec; John M Rimoldi; Rama S V Gadepalli; Joey P Granger Journal: Am J Physiol Regul Integr Comp Physiol Date: 2017-12-06 Impact factor: 3.619
Authors: Sean M Riordan; Douglas C Bittel; Jean-Baptiste Le Pichon; Silvia Gazzin; Claudio Tiribelli; Jon F Watchko; Richard P Wennberg; Steven M Shapiro Journal: Front Neurosci Date: 2016-08-18 Impact factor: 4.677
Authors: Ryan G Shiels; Josif Vidimce; Andrew G Pearson; Ben Matthews; Karl-Heinz Wagner; Andrew R Battle; Harry Sakellaris; Andrew C Bulmer Journal: Sci Rep Date: 2019-02-27 Impact factor: 4.379