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2,3-丁二酮单肟和 blebbistatin 对 Langendorff 灌流兔心机械电反馈的影响。

Modifications of mechanoelectric feedback induced by 2,3-butanedione monoxime and Blebbistatin in Langendorff-perfused rabbit hearts.

机构信息

Department of Medicine, Valencia University, Estudi General, Valencia, Spain.

出版信息

Acta Physiol (Oxf). 2012 Sep;206(1):29-41. doi: 10.1111/j.1748-1716.2012.02441.x. Epub 2012 May 16.

DOI:10.1111/j.1748-1716.2012.02441.x
PMID:22497862
Abstract

AIM

Myocardial stretching is an arrhythmogenic factor. Optical techniques and mechanical uncouplers are used to study the mechanoelectric feedback. The aim of this study is to determine whether the mechanical uncouplers 2,3-butanedione monoxime and Blebbistatin hinder or modify the electrophysiological effects of acute mechanical stretch.

METHODS

The ventricular fibrillation (VF) modifications induced by acute mechanical stretch were studied in 27 Langendorff-perfused rabbit hearts using epicardial multiple electrodes and mapping techniques under control conditions (n = 9) and during the perfusion of 2,3-butanedione monoxime (15 mM) (n = 9) or Blebbistatin (10 μm) (n = 9).

RESULTS

In the control series, myocardial stretch increased the complexity of the activation maps and the dominant frequency (DF) of VF from 13.1 ± 2.0 Hz to 19.1 ± 3.1 Hz (P < 0.001, 46% increment). At baseline, the activation maps showed less complexity in both the 2,3-butanedione monoxime and Blebbistatin series, and the DF was lower in the 2,3-butanedione monoxime series (11.4 ± 1.2 Hz; P < 0.05). The accelerating effect of mechanical stretch was abolished under 2,3-butanedione monoxime (maximum DF = 11.7 ± 2.4 Hz, 5% increment, ns vs baseline, P < 0.0001 vs. control series) and reduced under Blebbistatin (maximum DF = 12.9 ± 0.7 Hz, 8% increment, P < 0.01 vs. baseline, P < 0.0001 vs. control series). The variations in complexity of the activation maps under stretch were not significant in the 2,3-butanedione monoxime series and were significantly attenuated under Blebbistatin.

CONCLUSION

The accelerating effect and increased complexity of myocardial activation during VF induced by acute mechanical stretch are abolished under the action of 2,3-butanedione monoxime and reduced under the action of Blebbistatin.

摘要

目的

心肌牵张是一种致心律失常因素。光学技术和机械解偶联剂被用于研究力学电反馈。本研究的目的是确定机械解偶联剂 2,3-丁二酮单肟和 Blebbistatin 是否会阻碍或改变急性机械牵张的电生理效应。

方法

在 27 只 Langendorff 灌注兔心的心脏中,使用心外膜多电极和映射技术,在对照条件下(n=9)和在灌注 2,3-丁二酮单肟(15mM)(n=9)或 Blebbistatin(10μm)(n=9)的情况下,研究急性机械牵张引起的心室颤动(VF)的变化。

结果

在对照系列中,心肌牵张增加了激活图的复杂性和 VF 的主导频率(DF),从 13.1±2.0Hz 增加到 19.1±3.1Hz(P<0.001,增加 46%)。在基线时,2,3-丁二酮单肟和 Blebbistatin 系列的激活图复杂性较低,2,3-丁二酮单肟系列的 DF 较低(11.4±1.2Hz;P<0.05)。在 2,3-丁二酮单肟作用下,机械牵张的加速作用被消除(最大 DF=11.7±2.4Hz,增加 5%,与基线相比无统计学意义,与对照系列相比 P<0.0001),在 Blebbistatin 作用下,这种作用被减弱(最大 DF=12.9±0.7Hz,增加 8%,与基线相比 P<0.01,与对照系列相比 P<0.0001)。在 2,3-丁二酮单肟系列中,牵张引起的激活图复杂性的变化不显著,而在 Blebbistatin 作用下,这种变化显著减弱。

结论

急性机械牵张引起的 VF 期间心肌激活的加速作用和复杂性增加,在 2,3-丁二酮单肟的作用下被消除,在 Blebbistatin 的作用下被减弱。

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