Mechanism of interruption of atrial flutter by moricizine. Electrophysiological and multiplexing studies in the canine sterile pericarditis model of atrial flutter.
Mechanism of interruption of atrial flutter by moricizine. Electrophysiological and multiplexing studies in the canine sterile pericarditis model of atrial flutter.
复制标题
莫雷西嗪阻断心房扑动的机制。
DOI：
10.1161/01.cir.89.6.2860
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发表时间：
1994
期刊：
影响因子：
37.8
通讯作者：
Waldo,AL
中科院分区：
文献类型：
--
作者：
Ortiz,J;Nozaki,A;Shimizu,A;Khrestian,C;Rudy,Y;Waldo,AL
背景：据说莫里西嗪对心脏传导有强有力的影响，但对心脏的难治性影响很小或没有影响。方法与结果观察莫里嗪（2mg /kg IV）对11只犬无菌心包炎后2 ~ 4天心房扑动的影响。研究了清醒非镇静状态下9只犬的10次稳定心房扑动，麻醉开胸状态下6只犬的7次稳定心房扑动。在清醒状态下，通过将心外膜电极置于特定心房位置，记录窦性心律超速起搏过程中，莫西嗪对心房兴奋性、心房有效不应期和房内传导时间的影响。Moricizine延长了所有发作的心房扑动周期长度，从平均133 +/- 9毫秒到172 +/- 27毫秒（P < 0.001），然后终止10次发作中的7次。Moricizine使心房兴奋性阈值从平均2.3 +/- 1.4 mA增加到3.3 +/- 2.2 mA (P < 0.01)，使心房内传导时间（从终末沟到左心房后下段）从平均58 +/- 6毫秒延长到64 +/- 5毫秒（P < 0.005）。心房有效不应期由166 +/- 20毫秒延长至174 +/- 24毫秒（P < 0.05）。在开胸研究中，莫西嗪使心房扑动周期长度从平均150 +/- 15毫秒延长至216 +/- 30毫秒（P < .001），然后在所有7次发作中终止心房扑动。通过对右心房自由壁95个双极点的同时多位点定位显示，心房扑动周期长度的延长要么是由于心房扑动重入回路中一个慢传导区域的传导进一步减慢（5次），要么是由于一个慢传导区域的传导进一步减慢加上第二个慢传导区域的发展（2次）。可重入电路其余部分的传导时间变化可以忽略不计（占总变化的10.9 +/- 8.7%）。在所有7次发作中，最后一次循环再入波阵面阻塞在一个传导缓慢的区域。结论莫替西嗪(1)延长心房扑动周期长度，主要是通过减缓重入回路慢传导区域的传导，(2)通过阻断重入回路慢传导区域的循环重入波前终止心房扑动，(3)有效阻断本犬模型中原本稳定的心房扑动。moricizine产生这些影响的原因并不能通过其对窦性心律期间的心房传导时间和顽固性的影响来解释。慢传导区域的局部传导变化是导致周期长度延长和心房扑动终止的原因，而不是传统的正反相互作用波长概念。
BACKGROUNDMoricizine is said to have potent effects on cardiac conduction but little or no effect on cardiac refractoriness.METHODS AND RESULTSThe effects of moricizine (2 mg/kg IV) on induced atrial flutter were studied 2 to 4 days after the creation of sterile pericarditis in 11 dogs. Ten episodes of stable atrial flutter before and after the administration of moricizine were studied in 9 dogs in the conscious, nonsedated state, and 7 episodes were studied in 6 dogs in the anesthetized, open chest state. In the conscious state, the effects of moricizine on atrial excitability, atrial effective refractory period, and intra-atrial conduction times were studied by recording during overdrive pacing of sinus rhythm from epicardial electrodes placed at selected atrial sites. Moricizine prolonged the atrial flutter cycle length in all the episodes, from a mean of 133 +/- 9 to 172 +/- 27 milliseconds (P < .001), and then terminated 7 of the 10 episodes. Moricizine increased the atrial threshold of excitability from a mean of 2.3 +/- 1.4 to 3.3 +/- 2.2 mA (P < .01) and prolonged intra-atrial conduction times (measured from the sulcus terminalis to the posteroinferior left atrium) from a mean of 58 +/- 6 to 64 +/- 5 milliseconds (P < .005). Prolongation of the atrial effective refractory period from 166 +/- 20 to 174 +/- 24 milliseconds (P < .05) was observed only at the sulcus terminalis site. In the open chest studies, administration of moricizine prolonged the atrial flutter cycle length from a mean of 150 +/- 15 to 216 +/- 30 milliseconds (P < .001) and then terminated the atrial flutter in all 7 episodes. As demonstrated by simultaneous multisite mapping from 95 bipolar sites on the right atrial free wall, the atrial flutter cycle length prolongation was either due to further slowing of conduction in an area of slow conduction in the reentrant circuit of the atrial flutter (5 episodes) or further slowing of conduction in an area of slow conduction plus the development of a second area of slow conduction (2 episodes). The change in conduction times in the rest of the reentrant circuit was negligible (10.9 +/- 8.7% of the total change). In all 7 episodes, the last circulating reentrant wave front blocked in an area of slow conduction.CONCLUSIONSMoricizine (1) prolongs the atrial flutter cycle length, primarily by slowing conduction in an area of slow conduction in the reentrant circuit, (2) terminates atrial flutter by causing block of the circulating reentrant wave front in an area of slow conduction of the reentrant circuit, and (3) effectively interrupts otherwise stable atrial flutter in this canine model. The reason for these effects of moricizine are not readily explained by its effects on global atrial conduction times and refractoriness studied during sinus rhythm. Local changes in conduction in an area(s) of slow conduction are responsible for both cycle length prolongation and atrial flutter termination rather than the traditional wavelength concept of head-tail interaction.