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 defibri llation efficacy. We investigated whether a Class III drug simply shifts th e dose-response curve for defibrillation or more extensively alters the cur ve. Forty-five dogs were divided into four groups according to the shock wa veform 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 convent ional transcardiac DFT, dose-response curves were obtained by fitting the r esults of 40 fibrillation-defibrillation sequences at five shock strengths to a logistic model. MS-551 significantly decreased DFT regardless of the s hock 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 <. 0.0 05]). The dose-response curves in dogs treated with MS-551 had a gentler sl ope than those without treatment, and the ratio of the voltages correspondi ng to 50% and 90% defibrillation success (V90/V50) was significantly greate r in the MS-551 group (monophasic: 1.21 +/- 0.06 vs 1.62 +/- 0.42 [P < 0.00 5], 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 corresp onding to relatively higher success rate (similar to 90%) less markedly tha n that for moderate success rate (similar to 50%). These results suggest th at a Class III drug does not simply shift the dose response curve in propor tion to the change in DFT, but more extensively alters its configuration.