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Effects of consecutive use of isoproterenol/adenosine on ischaemia-reperfusion injury and cardioprotection in rat heart

A Al-Ahmadi, FC Howarth, I Khaliulin, S Suleiman
Published in : HAMDAN MEDICAL JOURNAL ; Vol 8, No 4 (2015): Supplement Issue
DOI : 10.7707/hmj.533

Abstract


Introduction: Ischaemia of the heart can arise from narrowing of coronary arteries by atherosclerosis or during cardiac surgery when blood is diverted away from the heart. Reperfusion of the heart after a relatively long period of ischaemia results in cardiomyocyte death, which may be caused by the generation of free radicals. Consecutive activation of protein kinase A (PKA) and protein kinase C (PKC) using isoproterenol/adenosine is a novel intervention but has been validated using only non-physiological concentrations of isoproterenol.

Objectives: To investigate the effects of the consecutive use of clinically relevant concentrations of isoproterenol/adenosine on the recovery of hearts following global ischaemia in rat heart.

Materials and methods: Hearts (≈ 0.75g) from male Wistar rats (250– 260g) were rapidly removed and mounted on a Langendorff perfusion apparatus. Hearts were perfused under constant pressure (55mmHg) at 37°C with Krebs– Henseleit solution. Haemodynamic function was recorded on a PowerLab data acquisition system (ADInstruments, Bella Vista, Australia) using a latex balloon placed in the left ventricle. After 33 minutes pre-ischaemia, global normothermic ischaemia (37°C) was induced for 30 minutes by switching off the pump followed by 120 minutes normothermic reperfusion (control group). In a second group (intervention), hearts were perfused with 5nM isoproterenol for 3 minutes followed by 5 minutes perfusion with 30μM adenosine following 25 minutes equilibration period. At the end of reperfusion, each heart was perfused with triphenyl tetrazolium chloride for 2 minutes to stain for viable tissue.

Results: During reperfusion, the isoproterenol/ adenosine group significantly improved recovery and considerably reduced infarction size compared with control.

Conclusions: The consecutive activation of PKA and PKC, induced by clinically relevant isoproterenol and adenosine, is protective against myocardial injury induced by 30-minute global ischaemia.

Acknowledgements: Professor Chris Howarth and Professor Saadeh Suleiman for supervising this project.

 


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