PHARMACOLOGICAL STUDIES OF K+ LOSS FROM ISCHEMIC MYOCARDIUM INVITRO - ROLES OF ATP-DEPENDENT K+ CHANNELS AND LACTATE-COUPLED EFFLUX

Perfused guinea-pig hearts were rendered ischaemic by 95% reductions in coronary flow. K+ and lactate release over the first 6 min of ischaemia were reduced by glibenclamide (described as a K(ATP)+ channel blocker), 2-deoxyglucose (inhibitor of lactate synthesis) and alpha-cyano-4-hydroxycinnamic acid (inhibitor of lactate transport). Glibenclamide did not selectively reduce K+ loss without affecting lactate release, as would be expected for a selective K(ATP)+ channel blocker. During a single 30 min period of ischaemia, a secondary release of K+ was observed corresponding to the onset of ventricular fibrillation, with no associated increase in lactate efflux, which appeared sensitive to glibenclamide. In conclusion, glibenclamide failed to reduce K+ loss in early ischaemia without reducing lactate release as would be expected for a selective K(ATP)+ channel blocker. Caution should be exercised when using glibenclamide as a specific blocker of K(ATP)+, channels in the absence of measurements of metabolic parameters.