Identification and role of the adenosine A3 receptor in the recovery of cardiac tissue from ischaemia.

James, Sian Elizabeth 2007. Identification and role of the adenosine A3 receptor in the recovery of cardiac tissue from ischaemia. PhD Thesis, Cardiff University.

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Abstract

The adenosine A3 receptor is one of the suspected effectors of intrinsic preconditioning. Its intrinsic ligand, adenosine is produced by ischaemic tissue, where it acts to cause a preconditioning effect, rendering the tissue resistant to damage by any subsequent ischaemia. Adenosine A3 receptor stimulation has previously been shown mediate the recovery of the heart following ischaemia. It is thought to be involved in alleviating temporary stunning and modulating infarction by the mechanisms by which it evokes preconditioning. Using a variety of cardiac ischaemia models from rat tissue, we investigated the effect of a selective A3 receptor agonist on ischaemic cardiac tissues and whether it is possible to evoke a cardioprotective effect by stimulation of adenosine A3 receptor alone. The administration of selective A3 receptor agonist alleviated post-ischaemic contractile dysfunction in the isolated left atria. No effect was found in right ventricle strips, while in the Langendorff heart it was found that there was a pro-infarct effect, with no observed effect of contractility. Attempts to classify the effects as being adenosine A3 receptor -mediated or another adenosine subtype by use of selective antagonists was difficult for reasons discussed. Using immunological methods is was possible to identify a protein specific for the adenosine A3 receptor in membrane fractions obtained from both normoxic and ischaemic rat left atria. This strengthens the claim that the effect reported in this thesis are adenosine A3 receptor mediated. In summary it is recommended that A3 receptor manipulation and its effect on post-ischaemic recovery remains a viable route of further investigation. The work in this field is required to form new strategies for the treatment coronary heart disease and other cardiac conditions.

Item Type:	Thesis (PhD)
Status:	Unpublished
Schools:	Pharmacy
Subjects:	R Medicine > RM Therapeutics. Pharmacology
ISBN:	9781303182570
Funders:	British Heart Foundation
Date of First Compliant Deposit:	30 March 2016
Last Modified:	19 Mar 2016 23:33
URI:	https://orca.cardiff.ac.uk/id/eprint/55726

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