Pell, Theresa Jane; (1999) The involvement of ATP-sensitive potassium channels in novel forms of myocardial protection. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Introduction. Ischaemic heart disease is the main cause of mortality and disability in the United Kingdom. Current treatments are not wholly successful, therefore, new therapies are required. One area of research that may provide such a treatment is ischaemic preconditioning, in which transient myocardial ischaemia results in acute and delayed protection against sustained ischaemia. The aims of this study were to investigate one aspect of the underlying mechanism, namely the role of ATP-sensitive potassium (KATP) channels, in novel forms of myocardial protection. Methods. In vivo rabbit models of myocardial infarction, 30 minutes coronary artery occlusion followed by two hours reperfusion, were used. channels were studied in delayed protection afforded by heat stress (15 minutes at 42 °C) or ischaemic preconditioning (four cycles of five minutes myocardial ischaemia each separated by 10 minutes reperfusion), and, in addition, acute and delayed protection afforded by transient ischaemia of the kidney (10 minutes renal artery occlusion). The effects of ischaemic preconditioning and heat stress on mRNA expression of the KATP channel subunit Kir6.2 were also determined. Results. Blockade of KATP channels prevented delayed myocardial protection afforded by heat stress at 24 hours and acute protection induced by transient renal ischaemia. Ischaemic preconditioning and transient renal ischaemia failed to elicit a delayed phase of protection at 48 hours in this study. Neither heat stress nor ischaemic preconditioning resulted in changes in Kir6.2 mRNA expression at one, three or 24 hours. Conclusions. KATP channels, perhaps located in the mitochondria, appear to be involved in delayed protection afforded by heat stress and acute myocardial protection induced by transient renal ischaemia. It seems that protection does not occur via increased expression of Kir6.2 containing KATP channels.

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