The electrophysiological and mechanical effects of 2,3-butane-dione monoxime and cytochalasin-D in the Langendorff perfused rabbit heart
The electrophysiological and mechanical effects of 2,3-butane-dione monoxime and cytochalasin-D in the Langendorff perfused rabbit heart
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DOI：
10.1113/expphysiol.2003.026732
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发表时间：
2004-03-01
影响因子：
2.7
通讯作者：
Smith, GL
中科院分区：
文献类型：
--
作者：
Kettlewell, S;Walker, NL;Smith, GL
减少收缩的程序用于促进膜电位的光学测量，但尚不清楚它们在多大程度上影响心脏的兴奋性。本研究检测了一系列细胞外[Ca ~（2+）]（0.7-2.5 mmol ~（-1））、2，3-丁二酮单肟（BDM; 1-20 mmol ~（-1））和细胞松弛素D（CytoD; 1-5 mumol ~（-1））的电生理后果。方法.在离体兔心记录左心室基底心外膜表面的单相动作电位（MAP）。测量传导延迟（CD）和单相动作电位（MAPD（90））90%复极化的时间。在[Ca 2 +]为1.9 mmol-1时，研究了BDM和Cyto-D对恢复的影响。使用标准S1-S2方案生成MAPD 90的呼吸曲线。结果所有操作均降低左心室发展压（LVDP）：0.7 mmol 1（-1）Ca 2+至对照值的74.0 +/-6.1%，20 mmol 1（-1）BDM至对照值的4.5 +/-1.0%，5 mumol 1（-1）Cyto-D至对照值的12.8 +/- 3.5%。CD从对照值（33.3 +/- 1.0 ms，n = 16）降至0.7 mumol 1（-1）Ca 2+中的93.0 +/- 2.2%，但在20 mmol 1（-1）BDM中增至133.7 +/- 10.5%，在5 mmol 1（-1）Cyto-D中增至127.4 +/- 10.6%。在350 ms起搏周期长度时，MAPD（90）（对照组= 119.6 +/- 1.7 ms n = 16）因细胞外[Ca 2 +]减少而延长。在控制起搏频率下，BDM对MAPD 90无影响。Cyto-D在研究的最高浓度（5 μ mol 1（-1））下引起显著延长（至对照的115.0 +/- 3.0%，n = 6）。BDM（20 mmol 1（-1））和Cyto-D（3 mumol 1（-1））均使恢复曲线变平，但两种药物均未改变最大MAPD 90。结论. 1.9 mmol 1（-1）的细胞外[Ca 2 +]与中等剂量的Cyto-D（3 mumol 1（-1））联合使用可降低收缩性，对固定起搏周期长度下的动作电位持续时间和传导的影响最小。然而，BDM和Cyto-D都对电恢复有显著影响。
Procedures that reduce contraction are used to facilitate optical measurements of membrane potential, but it is unclear to what extent they affect the excitability of the heart. This study has examined the electrophysiological consequences of a range of extracellular [Ca2+] (0.7-2.5 mmol 1(-1)), 2,3-butane-dione monoxime (BDM; 1-20 mmol 1(-1)) and cytochalasin-D (CytoD; 1-5 mumol 1(-1)). Methods. Monophasic action potentials (MAPs) were recorded from the basal epicardial surface of the left ventricle of isolated rabbit hearts. Conduction delay (CD) and time to 90% repolarisation of the monophasic action potential (MAPD(90)) were measured. The effects of BDM and Cyto-D on restitution were studied at a [Ca2+] of 1.9 mmol 1(-1). Restitution curves for MAPD90 were generated using a standard S1-S2 protocol. Results. All manoeuvres decreased left ventricular developed pressure (LVDP): 0.7 mmol 1(-1) Ca2+ to 74.0 +/- 6.1%, 20 mmol 1(-1) BDM to 4.5 +/- 1.0%, and 5 mumol 1(-1) Cyto-D to 12.8 +/- 3.5% of control value. CD decreased from a control value (33.3 +/- 1.0 ms, n = 16) to 93.0 +/- 2.2% in 0.7 mumol 1(-1) Ca2+, but increased to 133.7 +/- 10.5% in 20 mmol 1(-1) BDM and 127.4 +/- 10.6% in 5 mmol 1(-1) Cyto-D. At 350 ms pacing cycle length, MAPD(90) (control = 119.6 +/- 1.7 ms n = 16) was prolonged by reduced extracellular [Ca2+]. BDM had no effects on MAPD90 at control pacing rates. Cyto-D caused a significant prolongation (to 115.0 +/- 3.0% of control, n = 6) at the highest concentration studied (5 mumol 1(-1)). Both BDM (20 mmol 1(-1)) and Cyto-D (3 mumol 1(-1)) flattened the restitution curves but neither agent altered maximum MAPD90. Conclusions. Extracellular [Ca2+] of 1.9 mmol 1(-1) in conjunction with a moderate dose of Cyto-D (3 mumol 1(-1)) reduced contractility with minimal effects on action potential duration and conduction at a fixed pacing cycle length. However, both BDM and Cyto-D had pronounced effects on electrical restitution.