通道开通剂在与延迟复极化相关的节律异常中具有抗节律作用
L Carlsson1, C Abrahamsson, L Drews
1Department of Cardiovascular Pharmacology, Astra Hässle AB, Mölndal, Sweden.
Circulation
|April 1, 1992
概括
通道开放剂皮纳西迪尔及其类似物P1075和P1188在子中减少了药物诱导的多态心室动脉节律失常症 (PVTs). 这些化合物还消除了早期的脱极化后和触发活动,这表明某些心律失常的治疗潜力.
科学领域:
- 心血管药理学心血管药理学
- 电力生理学 电力生理学
- 离子通道调制 离子通道调制
背景情况:
- 重极化延迟药物可以诱导多态心室动脉节律失常症 (PVTs),一种Torsade de pointes的类型.
- 通道开放剂对PVTs的抗心律失常潜力需要研究.
研究的目的:
- 评估皮纳西迪尔及其皮里迪尔基亚诺瓜尼丁类同类 (P1075,P1188) 对克洛菲诱导的PVTs的抗失常作用.
- 研究这些化合物对早期脱极化后 (EAD) 和心脏电生理学中触发活动的影响.
主要方法:
- 在子体内使用克洛菲和甲索来诱导PVTs的实体研究,先处理皮纳西迪尔,P1075或P1188.8.
- 从子普金尼叶纤维和心室肌肉细胞进行体外电生理学记录,以评估动作潜力的持续时间,EAD和触发活动.
- 用glibenclamide进行药理封锁,以探索ATP敏感通道的作用.
主要成果:
- 皮纳西迪尔,P1075和P1188剂量取决于降低了由克洛菲诱导的PVTs的发生率.
- P1075和P1188表现出显著的抗心律失常作用,高剂量完全阻止了PVTs.
- 在实验室中,P1075消除了克洛菲诱导的EDS,并触发了Purkinje纤维的活性,这种效应被glibenclamide逆转.
- 迪尔提亚并没有减轻PVT的发生,而不是像pyridylcyanoguanidines.
结论:
- 对ATP敏感的通道激活剂在预防和治疗PVTs方面表现有前途.
- 这些发现表明,pyridylcyanoguanidines在管理与复极异常相关的心律失常方面具有治疗作用.
相关概念视频
Mechanism of Cardiac Arrhythmias
Arrhythmias are irregular heart rhythms occurring when the heart's electrical impulses become abnormal. These disturbances can lead to various symptoms, depending on their severity and the underlying cause. Some common factors contributing to arrhythmias include hypoxia, ischemia, electrolyte imbalances, excessive catecholamine exposure, drug toxicity, and muscle overstretching. Arrhythmias can be classified into two main types based on the rate and site of origin of abnormal heart rhythms.
Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers
Class I antiarrhythmic drugs are used to treat various types of arrhythmias or irregular heart rhythms. These drugs block the sodium (Na+) channels in the cardiac cells, thereby affecting the movement of electrical impulses across the heart. Class I antiarrhythmic drugs are divided into three subgroups: Class IA, Class IB, and Class IC, each with distinct mechanisms of action and effects on the heart.
Class 1A Antiarrhythmic Drugs: These drugs work by moderately blocking sodium channels,...
Class 1A Antiarrhythmic Drugs: These drugs work by moderately blocking sodium channels,...
Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers
Adrenergic stimulation generally impacts cardiac rate and rhythm. Specifically, stimulation of the β-adrenoceptors triggers an increase in intracellular calcium ion influx and pacemaker currents, which may cause arrhythmias. Catecholamines like adrenaline also demonstrate β2-adrenoceptor-mediated hypokalemia, impacting cardiac action potential and disrupting the normal cardiac rhythm. Class II antiarrhythmic drugs are β-adrenoceptor antagonists or β-blockers, which indirectly block calcium...
Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers
Class III antiarrhythmic drugs are a group of medications that can prolong action potentials in the heart. They achieve this by blocking potassium channels or enhancing inward currents from sodium channels. However, these drugs have a unique property of "reverse use-dependence," which is most pronounced at slower heart rates and can lead to torsades de pointes—a specific type of arrhythmia. However, it is essential to note that excessive QT interval prolongation—a measure of the heart's...
Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers
Class IV antiarrhythmic drugs, such as verapamil and diltiazem, block calcium channels. They primarily affect the heart, slowing the conduction in calcium-dependent tissues like the SA and AV nodes. These drugs manage reentrant supraventricular tachycardia (SVT) and reduce ventricular rate in atrial flutter/fibrillation.
Verapamil, a calcium channel blocker, inhibits calcium movement across myocardial cell membranes and vascular smooth muscle. This results in the dilation of coronary and...
Verapamil, a calcium channel blocker, inhibits calcium movement across myocardial cell membranes and vascular smooth muscle. This results in the dilation of coronary and...
Antiepileptic Drugs: Potassium Channel Activators
Ezocgabine or retigabine, an antiepileptic drug of remarkable efficacy, has revolutionized the management of seizures. It is a potassium channel activator, explicitly targeting the family of Q subtype potassium channels. It enhances the transmembrane potassium currents, regulating neuronal excitability. This action stabilizes the resting membrane potential, a pivotal factor in mitigating the hyperexcitability that characterizes epilepsy.
Ezogabine has gained approval as an adjunctive treatment...
Ezogabine has gained approval as an adjunctive treatment...


