Carr, Cornelia Sonia; (1997) Ischaemic preconditioning of human atrium: Mechanisms of myocardial protection. Doctoral thesis (Ph.D.), University College London (United Kingdom).

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Abstract

Ischaemic preconditioning, using a brief period of ischaemia and reperfusion, may protect the heart against ischaemic damage. This protection manifests itself in increased resistance to infarction, reperfusion-induced arrhythmias, contractile dysfunction, contracture and conservation of energy. This endogenous protective phenomenon has been shown to exist in all animal species as well as man. The mechanisms underlying ischaemic preconditioning have now been partly characterised in both animals and in the human. It would appear that adenosine receptor activation, protein kinase C mediation, Gi protein mediation and the possible opening of ATP-sensitive potassium (KATP) channels play a role in the protection conferred by ischaemic preconditioning. Therefore investigators are now examining the roles played by the KATP channel and the different adenosine receptor subtypes, which may vary between species. The series of experiments reported in this thesis involved the refining and validation of an isolated human atrial trabeculae model, and further investigation into the mechanisms underlying ischaemic preconditioning of human atrium. The opening of KATP channels had previously been implicated in ischaemic protection in this model; therefore, we conducted further work using a novel KATP channel opener, that does not alter action potential duration, to examine this effect more closely. In addition the effect of an orally administered KATP channel opener was also examined using the isolated atrial trabeculae model. Finally an investigation into the adenosine A1 and A3 receptor subtypes involvement in cardioprotection of human atrium was undertaken. The data presented demonstrate that novel KATP channel openers may provide protection to human atrium, even when administered pre-operatively to patients. The combination of an ischaemic preconditioning protocol and KATP channel opener exposure led to the abolition of the protection normally provided by these interventions when used alone. In addition, and for the first time, we provide evidence for the involvement of both the adenosine A1 and A3 receptor subtypes in cardioprotection of human atrium.

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