Pharmacological studies of K+ loss from ischaemic myocardium in vitro: 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.