The role of mitochondrial K ATP channels in antiarrhythmic effects of ischaemic preconditioning in dogs

In the canine a single brief (5 min) coronary artery occlusion protects the myocardium against the severe ventricular arrhythmias and reduces the ischaemic changes that result from a subsequent, more prolonged (25 min) occlusion. The main purpose of the present study was to examine whether mitochondrial K ATP channels are involved in this protection. In chloralose‐urethane anaesthetized dogs, preconditioning (PC) was induced by a single 5 min period occlusion of the left anterior descending (LAD) coronary artery, 20 min prior to a 25 min occlusion of the same artery. In some of these PC dogs 5‐hydroxydecanoate (5‐HD; 150 μg kg −1 min −1 by intracoronary infusion) was given over a period of 30 min either before, or after PC. In other dogs the mitochondrial K ATP channel opener diazoxide (1 mg kg −1 ; i.c.) was given, either alone or in the presence of 5‐HD. Control dogs (infused with saline) were simply subjected to a 25 min occlusion and reperfusion. Compared to controls, both PC and diazoxide significantly reduced the number of ventricular premature beats (VPBs; 295±67 to 89±28 and 19±11, respectively; P <0.05), the number of episodes of ventricular tachycardia (VT; 8.3±4.2 to 1.6±0.9 and 0.2±0.1; P <0.05) and the incidences of VT (100 to 43 and 33%; P <0.05) and ventricular fibrilation (VF; 60 to 0 and 17%; P <0.05) during the 25 min occlusion of the LAD. Further, 43% of the PC dogs and 58% of the diazoxide treated dogs survived the combined ischaemia‐reperfusion insult (cp. 0% in the controls; P <0.05). The protection afforded by PC and diazoxide was abolished by 5‐HD, especially when it was given prior to the PC occlusion. In the presence of 5‐HD, three out of 10 dogs fibrillated during the PC occlusion and another three dogs died following reperfusion. Furthermore, there were no survivors in this group from the prolonged ischaemia/reperfusion insult. 5‐HD given after PC only attenuated the antiarrhythmic protection. Opening of mitoK ATP channels prior to ischaemia by preconditioning and diazoxide protects the myocardium against ischaemia and reperfusion‐induced arrhythmias. This protection is abolished if the opening of these channels is prevented by the prior administration of 5‐HD but only attenuated if 5‐HD is given after preconditioning. The results indicate that opening of mitoK ATP channels prior to ischaemia is mandatory for protection against ischaemia and reperfusion‐induced arrhythmias.British Journal of Pharmacology (2002) 137 , 1107–1115. doi: 10.1038/sj.bjp.0704966