Lee S D, Newman D, Ham M, Dorian P
Division of Cardiology, St. Michael's Hospital, Toronto, Ontario, Canada.
J Am Coll Cardiol. 1997 Jan;29(1):100-5. doi: 10.1016/s0735-1097(96)00423-8.
We sought to determine the electrophysiologic mechanisms explaining the efficacy of combination therapy with DL-sotalol and a type Ia drug in the treatment of ventricular tachycardia (VT).
Combination antiarrhythmic drug therapy with low dose DL-sotalol plus a type Ia antiarrhythmic agent has been shown to prevent spontaneous and induced VT. The mechanisms underlying the efficacy of this drug combination have not been fully elucidated.
We studied 32 patients with spontaneous sustained VT by using programmed electrical stimulation in the drug-free condition and after treatment with DL-sotalol (average dose [mean +/- SE] 151 +/- 8 mg/day) and a class Ia agent (quinidine, 1,337 +/- 59 mg/day, or procainamide, 2,083 +/- 327 mg/day). Sustained VT was induced in all patients at baseline study, and induction was reattempted during drug therapy. Monophasic action potential duration at 90% repolarization (APD90) and ventricular effective refractory period (ERP) were recorded with use of a contact electrode.
Ventricular ERP increased from 258 +/- 4 ms at baseline to 310 +/- 6 ms at a 600-ms drive cycle length (DCL600) with treatment (p < 0.001). APD90 increased from 288 +/- 6 ms by +10.1% at DCL600 and from 267 +/- 7 ms by +13.3% at a 400-ms drive cycle length (DCL400) (p < 0.001). Paced QRS duration increased from 141 +/- 3 to 158 +/- 6 ms at DCL400 (p < 0.05). At baseline, the shortest achieved coupling interval between successive propagated extrastimuli decreased progressively with respect to the first extrastimulus, following double and triple extrastimuli, at both DCL600 (-14.0% and -20.0%, respectively) and at DCL400 (-16.4% and -22.4%, respectively). This "peeling back" of refractoriness was attenuated on therapy with sotalol plus a class Ia antiarrhythmic agent to -6.7% and -10.5% (DCL600, p < 0.05), and -8.1%, -9.5% (DCL400, p < 0.05), for double and triple extrastimuli, respectively. The absolute prolongation of functional refractory periods by the drug combination increased with successive extrastimuli, from 55 +/- 6 ms for the V1V2 interval to 75 +/- 6 ms for V2V3 and 67 +/- 6 ms for V3V4 at DCL600, and from 51 +/- 5 ms for V1V2 to 69 +/- 6 ms for V2V3 and 74 +/- 7 ms for V3V4 at DCL400 (p < 0.001).
The combination of low dose sotalol and a class Ia agent greatly prolongs refractoriness. The magnitude of the effect increases at shorter coupling intervals.
我们试图确定解释DL - 索他洛尔与I a类药物联合治疗室性心动过速（VT）疗效的电生理机制。
低剂量DL - 索他洛尔联合I a类抗心律失常药物的联合抗心律失常药物治疗已被证明可预防自发性和诱发性VT。这种药物联合疗效的潜在机制尚未完全阐明。
我们通过在无药物状态下以及用DL - 索他洛尔（平均剂量[均值±标准误]151±8mg/天）和I a类药物（奎尼丁，1337±59mg/天，或普鲁卡因胺，2083±327mg/天）治疗后，使用程序电刺激研究了32例自发性持续性VT患者。在基线研究时所有患者均诱发出持续性VT，并在药物治疗期间再次尝试诱发。使用接触电极记录90%复极化时的单相动作电位持续时间（APD90）和心室有效不应期（ERP）。
治疗后，心室ERP在600ms驱动周期长度（DCL600）时从基线的258±4ms增加到310±6ms（p<0.001）。APD90在DCL600时从288±6ms增加了10.1%，在400ms驱动周期长度（DCL400）时从267±7ms增加了13.3%（p<0.001）。在DCL400时，起搏QRS波持续时间从141±3ms增加到158±6ms（p<0.05）。在基线时，在DCL600（分别为-14.0%和-20.0%）和DCL400（分别为-16.4%和-22.4%）时，连续传导的额外刺激之间达到的最短耦合间期相对于第一个额外刺激随着双额外刺激和三额外刺激逐渐缩短。索他洛尔联合I a类抗心律失常药物治疗后，这种不应期的“剥脱”在双额外刺激和三额外刺激时分别减弱至-6.7%和-10.5%（DCL600，p<0.05），以及-8.1%，-9.5%（DCL400，p<0.05）。药物联合使功能性不应期的绝对延长随着连续额外刺激而增加，在DCL600时，V1V2间期从55±6ms增加到V2V3的75±6ms和V3V4的67±6ms，在DCL400时，V1V2从51±5ms增加到V2V3的69±6ms和V3V4的74±7ms（p<0.001）。
低剂量索他洛尔与I a类药物联合可显著延长不应期。在较短耦合间期时，这种效应的幅度增加。
