Arrhythmia mechanism

Manning, A.S. and Hearse, D.J. (1984). Reperfusion-induced arrhythmias mechanisms and prevention. J. Mol. Cell. Cardiol. 16, 497-518. 

Make a firm diagnosis. A firm arrhythmia diagnosis should be established. For example, the misuse of verapamil in patients with ventricular tachycardia mistakenly diagnosed as supraventricular tachycardia can lead to catastrophic hypotension and cardiac arrest. As increasingly sophisticated methods to characterize underlying arrhythmia mechanisms become available and are validated, it may be possible to direct certain drugs toward specific arrhythmia mechanisms. 

The anticipated outcome from this change in paradigm is the development of a non-clinical, standardised in vitro assay that determines the effects of drugs on the major cardiac ion channels and provide an assessment of the potential to precipitate clinical proarrhythmia, obviate conduct of the clinical TQT study and facilitate more efficient drug discovery efforts. In order to understand the fundamentals of this novel paradigm, it is important to review fundamental cardiac electrophysiology including basic ion channel biophysics as well as review some fundamental cardiac arrhythmia mechanisms to achieve this alternate approach. 

Cardiac arrhythmias are an important cause of morbidity and mortality approximately 400,000 people per year die from myocardial infarctions (MI) in the United States alone. Individuals with MI exhibit some form of dysrhythmia within 48 h. Post-mortem examinations of MI victims indicate that many die in spite of the fact that the mass of ventricular muscle deprived of its blood supply is often quite small. These data suggest that the cause of death is ventricular fibrillation and that the immediate availability of a safe and efficacious antiarrhythmic agent could have prolonged a number of Hves. The goals of antiarrhythmic therapy are to reduce the incidence of sudden death and to alleviate the symptoms of arrhythmias, such as palpitations and syncope. Several excellent reviews of the mechanisms of arrhythmias and the pharmacology of antiarrhythmic agents have been pubflshed (1,2). 

Facilitates GI transit/mechanical intestinal allodynia Cardiac arrhythmia... 

A cell may produce early afterdepolarizations that are depolarization during incomplete repolarization. This is possible if the action potential is considerably prolonged. This is the typical mechanism for elicitation of Torsade de Pointes arrhythmia, a typical complication of class III antiarrhythmics and many other drugs. 

Intravenous administration of magnesium sulfate (1-5 g) is used for the termination of torsade de pointes arrhythmia. The underlying electrophysiological mechanism is not well understood. It includes changes of the current-voltage relationship of Iki and Ca2+ channel blockade. 

One eritical factor that has been neglected in considering mechanisms of cardiac fatalities is the timeframe for various types of toxicities. For example, a majority of cocaine-related fatalities and near fatalities reported from emergency rooms are attributed to one or more types of cardiac ischemic or hypertensive episodes (Isner et al. 1986). Thus, these studies may discount the cocaine-induced arrhythmias and conduction defects as important direct causes of fatalities. Yet, if coroner reports are used as data sources (Virmani et al. 1988 Wetli and Wright 1979 Mittleman and Wetli 1984), there are great numbers of deaths in which pulmonary effusion and lack of evidence for coronary occlusion, acute myocardial infarction, or... 

The mechanism of abnormal impulse conduction is traditionally referred to as reentry. Reentry is often initiated as a result of an abnormal premature electrical impulse (abnormal automaticity) therefore, in these situations, the mechanism of the arrhythmia is both abnormal impulse formation (automaticity) and abnormal impulse conduction (reentry). In order for reentry to occur, three conditions must be present. There must be (1) at least two pathways down which an electrical impulse may... 

Reentry Circular movement of electrical impulses a mechanism of many arrhythmias. 

---