Pro-fibrillatory Effects of KATP Channel Opener and the Action Potential Duration Restitution Kinetics in Isolated Swine Right Ventricle

ABSTRACT

BACKGROUND AND OBJECTIVES: It remains to be defined how K[ATP] Channel Opener facilitates to induce ventricular arrhythmias. The purposes of this study are to assess the effects of K[ARP] Channel Opener, PCO400, on the action potential duration (APD) and APD restitution (APDR) kinetics, and their relationship with induction of ventricular tachycardia (VT)/fibrillation (VF), pro-fibrillatory effects. MATERALS AND METHODS: We recorded transmembrane potentials (TMPs) by microelectrode technique to explore the effects of PCO400 in ninetecn isolated perfused swine right ventricles. TMPs were recorded on the endoeardial side at the concentrations 0 micrometer, 1 micrometer, 2.5 micrometer, 5 micrometer, 10 micrometer, and washed-out period (1 hour). Ventricular refractory periods were measured while scanning djastole with premature ventricular beats during pacing at the cycle length of 600 ms at each concentration. The maximal slopes (Smax) of APDR were calculated with the data of S1S2 pacing and VF. RESULTS: PCO400 reduced APD90 (208+/-76 ms to 41+/-9 ms during S1, p<0.001, 111+/-32 ms to 54+/-28 ms during VF, p<0.001). While PCO400 tended to increase Smax of APDR at the concentration of 1 micrometer (0.6 to 0.7 by S1S2, 2.3 to 3.0 during VF), it reduced Smax at higher concentrations (-0.01 by S1-S2, p<0.05;-1.1 during VF, p<0.01). The increment of PCO400 concentration was associated with facilitated VT/VF induction (24.4% to 100%, p<0.001). Spontaneous VF induction rate was the highest at 1 micrometer (38.5%) which resulted in the highest Smax. CONCLUSION: PCO400 shows pro-fibrillatory effect by APD reduction and dynamic changes of Smax, Smax is closely related to spontancous induction of VT/VF, and APD90 shortening below 70 ms is critical for the maintenance of VT/VF.