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Chapter-21 Antiarrhythmics

BOOK TITLE: Drug Screening Methods

Author
1. Mohanty Ipseeta
ISBN
9788180613975
DOI
10.5005/jp/books/10243_21
Edition
1/e
Publishing Year
2004
Pages
14
Author Affiliations
1. MGM Medical College, Sector-16, Kamothe, Navi Mumbai 410 705, Maharashtra (India), All India Institute of Medical Sciences, New Delhi, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110029, India
Chapter keywords
arrhythmia, myocardium, ventricular extrasystole, ventricular tachycardia, ventricular fibrillation, cell culture technique, ventricular arrhythmias, torsade de pointes, isolated ventricular myocytes, isolated guinea pig papillary muscle, electrical stimulation, intracellular action potential, ventricular guinea pig papillary muscle, retrograde direction, aorta, oxygenated saline solutions, acetylcholine, potassium-induced arrhythmia, antiarrhythmic drugs, chemically induced arrhythmia, aconitine antagonism in rats

Abstract

Arrhythmia is the disturbance in the rhythm of myocardium. It may result because of abnormal automaticity or impaired conduction or both. Arrhythmia is manifested as ventricular extrasystole, ventricular tachycardia, and ventricular fibrillation. Cell culture technique is discussed. Ventricular arrhythmias, especially torsade de pointes, can be evaluated using isolated ventricular myocytes. In vitro models are discussed. Isolated guinea pig papillary muscle is explained. Action potential and refractory period in isolated guinea pig papillary muscle is discussed. Following the electrical stimulation, intracellular action potential in the left ventricular guinea pig papillary muscle is recorded. The basic principle involved in Lagendorff technique is that heart is perfused in a retrograde direction from the aorta either at constant pressure or constant flow with oxygenated saline solutions. Acetylcholine and potassium-induced arrhythmia is explained. In vivo models used to screen antiarrhythmic drugs can be divided into five groups. Chemically induced arrhythmia, aconitine antagonism in rats, digoxin-induced arrhythmia in guinea pigs, strophanthin or ouabain-induced arrhythmia, adrenaline-induced arrhythmia, calcium-induced arrhythmia, electrically induced arrhythmia, ventricular fibrillation electrical threshold, and programmed electrical stimulation-induced arrhythmia are described. Exercise-induced ventricular fibrillation is discussed. Tests combining coronary constriction with physical exercise may resemble most closely the situation in coronary patients. Sudden coronary death is one of the leading causes of death in developed countries. The trachea is cannulated and the animals are maintained on artificial respiration. The jugular vein is cannulated for the administration of test drug or saline. Arrhythmias can be induced directly by ischemia or by reperfusion. By ischemia-induced infarction or by coronary ligation, several phases of arrhythmia can be studied. Mortality in dogs after coronary occlusion with a two-stage ligation procedure is lower than one-stage ligation method. Genetically induced arrhythmia explains genetic arrhythmia. Antiarrhythmic drugs exert their effects largely by modulating conduction velocity, or refractory period duration, or both.

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