DOSE-DEPENDENT INHIBITION OF STRETCH-INDUCED ARRHYTHMIAS BY GADOLINIUM IN ISOLATED CANINE VENTRICLES - EVIDENCE FOR A UNIQUE MODE OF ANTIARRHYTHMIC ACTION
DOSE-DEPENDENT INHIBITION OF STRETCH-INDUCED ARRHYTHMIAS BY GADOLINIUM IN ISOLATED CANINE VENTRICLES - EVIDENCE FOR A UNIQUE MODE OF ANTIARRHYTHMIC ACTION
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DOI：
10.1161/01.res.69.3.820
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发表时间：
1991-09-01
影响因子：
20.1
通讯作者：
TAYLOR, LK
中科院分区：
文献类型：
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作者：
HANSEN, DE;BORGANELLI, M;TAYLOR, LK
离体犬左心室的短暂舒张期扩张可预测心律失常。为了验证这一假设，这种心律失常可能介导的肌膜牵张激活的通道，我们试图抑制牵张诱导的心律失常与钆（Gd 3+），一个强大的牵张激活的通道阻滞剂。在实验中与6个孤立的犬心脏，左心室容积增加50毫秒，在早期的心脏，然后返回到初始体积的计算机伺服泵。在用Gd 3+治疗之前，调整牵张体积以产生95 +/- 2%的牵张诱导心律失常的概率。当给予Gd 3+（1-10 μ M）时，观察到牵张诱导的心律失常的剂量依赖性抑制。使用10 μ M Gd 3+时，牵张诱导心律失常的概率降低至13 +/- 10%（p < 0.05）。Gd 3+的洗脱完全逆转了这种效应。由于Gd 3+是一种钙通道拮抗剂，我们比较了Gd 3+与维拉帕米和硝苯地平对牵张性心律失常的影响。这些钙通道阻滞剂在显著抑制左心室压力发展的浓度（1 μ M）下给药时，对牵张诱导的心律失常没有明显的抑制作用。因此，我们的研究结果间接牵连牵张激活通道的起源牵张诱导的心律失常和抗心律失常药物作用的一种潜在的新模式，牵张激活通道的封锁提供了初步的证据。
Transient diastolic dilatation of the isolated canine left ventricle predictably elicits arrhythmias. To test the hypothesis that such arrhythmias may be mediated by sarcolemmal stretch-activated channels, we attempted to inhibit stretch-induced arrhythmias with gadolinium (Gd3+), a potent stretch-activated channel blocker. In experiments with six isolated canine hearts, left ventricular volume was increased for 50 msec during early diastole and then returned to initial volume by a computerized servopump. The stretch volume was adjusted to yield a probability of eliciting a stretch-induced arrhythmia of 95 +/- 2% before treatment with Gd3+. When Gd3+ (1-10-mu-M) was administered, dose-dependent suppression of stretch-induced arrhythmias was observed. The probability of a stretch-induced arrhythmia was reduced to 13 +/- 10% (p < 0.05) with 10-mu-M Gd3+. Washout of Gd3+ completely reversed this effect. Since Gd3+ is known to be a calcium channel antagonist, we compared the effect of Gd3+ on stretch-induced arrhythmias with that of verapamil and nifedipine. These calcium channel blockers produced no demonstrable inhibition of stretch-induced arrhythmias when administered at concentrations (1-mu-M) that substantially depressed left ventricular pressure development. Thus, our results indirectly implicate stretch-activated channels in the genesis of stretch-induced arrhythmias and provide preliminary evidence for a potential new mode of antiarrhythmic drug action-blockade of stretch-activated channels.