Potassium, acidosis and ventricular repolarisation during ischaemia

• Main Author: Bethell, H. W. L.
• Published: University of Cambridge 1996
• Subjects: 616.1
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.596607

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 K<SUB>ATP</SUB> channel inhibitor glibenclamide, so implicating the K<SUB>ATP</SUB> channel in the shortening process. In the second section it was established that low-flow ischaemia caused an early increase in <SUP>86</SUP>Rb efflux which was maximal during the phase of APD shortening. Once again glibenclamide abolished APD shortening but only reduced the degree of <SUP>86</SUP>Rb 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 K<SUB>ATP</SUB> 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 K<SUB>ATP</SUB> 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.