Dorian P, Newman D
Department of Medicine, St. Michael's Hospital, Toronto, Ont., Canada.
Cardiovasc Res. 1997 Feb;33(2):485-94. doi: 10.1016/s0008-6363(96)00214-3.
Drugs which primarily prolong cardiac refractoriness decrease defibrillation voltage and energy requirements in animals and man. The effect of such drugs on ventricular fibrillation itself is not well understood. We hypothesized that tedisamil, an investigational antiarrhythmic drug which blocks Ito and IK repolarizing potassium channels, would increase organization of epicardial electrograms during ventricular fibrillation while it lowered defibrillation energy requirements.
We measured magnitude-squared coherence, a measure of spatial organization, and ventricular fibrillation (VF) cycle length, ventricular effective refractory period (VERP), and monophasic action potential duration (APD90) as well as defibrillation energy threshold (E50) at baseline and after 150 micrograms/kg of tedisamil (n = 13) or saline control (n = 6) in an open chest dog model.
After tedisamil, mean magnitude-squared coherence increased by 132 +/- 133%, from 0.15 +/- 0.08 to 0.31 +/- 0.16 (P < 0.001); VF cycle length increased from 121 +/- 24 to 190 +/- 63 ms (P < 0.001) and became more regular, with the coefficient of variation between adjacent VF intervals decreasing from 14.1 +/- 6.9 to 3.9 +/- 2.2% (P < 0.001). Mean E50 decreased from 8.9 +/- 3.8 to 6.1 +/- 2.7 joules (P < 0.001); VERP increased from 158 +/- 30 to 201 +/- 31 ms (P < 0.001), and APD90 increased from 177 +/- 25 to 244 +/- 45 ms (P < 0.001) after tedisamil. No electrophysiologic parameter was changed after saline infusion.
Tedisamil increases both spatial coherence and temporal regularity of ventricular fibrillation. These effects on 'order' during VF may be in part responsible for the observed reduction in defibrillation energy requirements.
主要延长心脏不应期的药物可降低动物和人类的除颤电压及能量需求。此类药物对室颤本身的影响尚不完全清楚。我们推测，试验性抗心律失常药物替地沙米可阻断Ito和IK复极钾通道，在降低除颤能量需求的同时，会增加室颤期间心外膜电图的规整性。
在开胸犬模型中，我们测量了基线时以及给予150微克/千克替地沙米（n = 13）或生理盐水对照（n = 6）后的心电信号幅度平方相干性（一种空间规整性的测量指标）、室颤（VF）周期长度、心室有效不应期（VERP）、单相动作电位时程（APD90）以及除颤能量阈值（E50）。
给予替地沙米后，平均幅度平方相干性增加了132±133%，从0.15±0.08增至0.31±0.16（P < 0.001）；VF周期长度从121±24毫秒增至190±63毫秒（P < 0.001）且变得更规则，相邻VF间期的变异系数从14.1±6.9%降至3.9±2.2%（P < 0.001）。平均E50从8.9±3.8焦耳降至6.1±2.7焦耳（P < 0.001）；给予替地沙米后，VERP从158±30毫秒增至201±31毫秒（P < 0.001），APD90从177±25毫秒增至244±45毫秒（P < 0.001）。输注生理盐水后，无电生理参数发生改变。
替地沙米增加了室颤的空间相干性和时间规整性。这些对室颤期间“有序性”的影响可能部分解释了所观察到的除颤能量需求降低的现象。
