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Title: Potassium, acidosis and ventricular repolarisation during ischaemia
Author: Bethell, H. W. L.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 1996
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In the first section the relative severity of the insult produced by low-flow ischaemia was established through a series of experiments monitoring the change in intracellular pH, high energy phosphates and LVDP during zero-flow, low flow (7.5% of the control flow rate) and moderate flow ischaemia (30% of the control flow rate). This established that in terms of mechanical performance and bioenergetic status reducing the flow to 7.5% of the control flow rate produced a significant ischaemic insult. Separate experiments showed that low-flow ischaemia caused action potential duration (APD) shortening which could be prevented by the KATP channel inhibitor glibenclamide, so implicating the KATP channel in the shortening process. In the second section it was established that low-flow ischaemia caused an early increase in 86Rb efflux which was maximal during the phase of APD shortening. Once again glibenclamide abolished APD shortening but only reduced the degree of 86Rb efflux. In the third section the effects of respiratory and metabolic acidosis, both known modulators of channel function, on the APD were investigated to establish whether they caused KATP channel activation in isolation in whole heart. In conclusion, this study has demonstrated that in whole heart low-flow ischaemia causes potassium efflux as a result of KATP channel activation, with the subsequent APD shortening. Intracellular acidosis and increased intracellular lactate, both known modulators of channel function in isolated patches, cause activation of the channel in isolation in whole heart but their main effect is to cause APD lengthening. Hence, these metabolic changes during ischaemia may serve to reduce overall APD shortening.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available