The local intracoronary administration of methylene blue prevents the pronounced antiarrhythmic effect of ischaemic preconditioning.

Short periods of coronary artery occlusion (2 x 5 min) markedly reduce the severity of arrhythmias and the changes in ST-segment elevation and in the degree of inhomogeneity of conduction during a subsequent 25 min occlusion of the left anterior descending coronary artery in anaesthetized dogs. These changes were completely reversed if methylene blue (5 mg min-1) was infused into a side branch of the coronary artery throughout both the preconditioning and prolonged occlusions. These results suggest that the pronounced antiarrhythmic effects of preconditioning result from activation of guanylyl cyclase and result in increased levels of guanosine 3':5'-cyclic monophosphate.