Effect of a Class III Antiarrhythmic Drug on the Configuration of Dose Response Curve for Defibrillation

Antiarrhythmic agents with a Class III action are known to increase defibrillation efficacy. We investigated whether a Class III drug simply shifts the dose-response curve for defibrillation or more extensively alters the curve. Forty-five dogs were divided into four groups according to the shock waveform and the presence or absence of treatment with a novel Class III drug, MS-551 (2 mg/kg bolus + 0.02 mg/kg per min). In addition to the conventional transcardiac DFT, dose-response curves were obtained by fitting the results of 40 fibrillation-defibrillation sequences at five shock strengths to a logistic model. MS-551 significantly decreased DFT regardless of the shock waveform (control vs MS-551 = 306 +/- 79 V vs 229 +/- 72 V [monophasic shock, P < 0.05], or 227 +/- 42 V vs 176 +/- 26 V [biphasic shock, P < 0.005]). The dose-response curves in dogs treated with MS-551 had a gentler slope than those without treatment, and the ratio of the voltages corresponding to 50% and 90% defibrillation success (V90/V50) was significantly greater in the MS-551 group (monophasic: 1.21 +/- 0.06 vs. 1.62 +/- 0.42 [P < 0.005], biphasic: 1.20 +/- 0.05 vs 1.37 +/- 0.18 [P < 0.01]). The V90/DFT ratio was also significantly larger in the MS-551 group (monophasic: 1.22 +/- 0.12 vs 1.66 +/- 0.37 [P < 0.001]; biphasic: 1.19 +/- 0.11 vs 1.44 +/- 0.79 [P < 0.005]). Thus, this Class III drug decreased the shock strength corresponding to relatively higher success rate (approximately 90%) less markedly than that for moderate success rate (approximately 50%). These results suggest that a Class III drug does not simply shift the dose response curve in proportion to the change in DFT, but more extensively alters its configuration.