Heart cardiac electrophysiological effects

Wit, A. L., Hoffman, B. F. and Rosen, M. R.(1975) Electrophysiology and pharmacology of cardiac arrhythmias. IX. Cardiac electrophysiology effects of beta adrenergic receptor stimuiation and biockade. Part B. Amer. Heart J., 90, 665. 

The Class I agents decrease excitability, slow conduction velocity, inhibit diastoHc depolarization (decrease automaticity), and prolong the refractory period of cardiac tissues (1,2). These agents have anticholinergic effects that may contribute to the observed electrophysiologic effects. Heart rates may become faster by increasing phase 4 diastoHc depolarization in SA and AV nodal cells. This results from inhibition of the action of vagaHy released acetylcholine [S1-84-3] which, allows sympathetically released norepinephrine [51-41-2] (NE) to act on these stmctures (1,2). 

Cardiac glycosides exert electrophysiologic effects on the heart (via PANS) that include central vagal stimulation, facilitation of muscarinic activity, and sensitization of baroreceptors. These effects occur at conventional doses and in the absence of heart failure lead to a decrease in CO... 

Ca + CHANNEL BLOCK The major electrophysiological effects resulting from block of cardiac Ca + channels are in slow-response tissues, the sinus and AV nodes. Dihydropyridines such as nifedipine, which are used commonly in angina and hypertension, preferentially block Ca + channels in vascular smooth muscle their cardiac effects, such as heart rate acceleration, result principally from reflex sympathetic activation secondary to peripheral vasodilation. Only verapamil, diltiazem, and bepridil block Ca + channels in cardiac cells at clinically used doses. These drugs generally slow heart rate, although hypotension can cause reflex sympathetic activation and tachycardia. The velocity of AV nodal conduction decreases, so the PR interval increases. AV nodal block occurs as a result of decremental conduction and increased AV nodal refractoriness, which form the basis for the use of channel blockers in reentrant arrhythmias whose circuit involves the AV node, such as AV reentrant tachycardia. 

Liu T, Traebert M, Ju H, Suter W, Guo D, Hoffmann P, Kowey PR, Yan GX (Oct 2012). Differentiating electrophysiological effects and cardiac safety of drugs based on the electrocardiogram a blinded validation. Heart Rhythm 9(10) 1706-1715. 

Kenneback G, Bergfeldt L, ValUn H, Tomson T, Edhag O. Electrophysiologic effects and clinical hazards of carbamaze-pine treatment for neurologic disorders in patients with abnormahties of the cardiac conduction system. Am Heart J 1991 121 (5) 1421-9. 

Zipes DP, Miyazaki T. The autonomic nervous system and the heart basis for understanding interaction and effects on arrhythmia development. In Zipes DP, Jalife J, eds. Cardiac Electrophysiology From Cell to Bedside. Philadelphia WB Saunders, 1990. 

The general cardiodynamic effects of cardiac glycosides are quite complex because of the combination of their direct action on the heart and indirect action, which changes the electrophysiological properties of the heart (automatism, conductivity, and excitability). 

The side-effects of cardiac glycosides are mostly caused by electrophysiological/neuronal phenomena. Gastro-intestinal adverse reactions are probably triggered by effects on the central nervous system. Various types of cardiac arrhythmias are caused by the influence of the drugs on nodal tissues in the heart. The risk of arrhythmia is strongly enhanced by low plasma potassium concentrations. 

Ventricular fibrillation is electrical anarchy of the ventricle resulting in no cardiac output and cardiovascular collapse. Death wiU ensue rapidly if effective treatment measures are not taken. Patients who die abruptly (within 1 hour of initial symptoms) and unexpectedly (i.e., sudden death) usually have ventricular fibrillation recorded at the time of death. Sudden cardiac death accounts for about 400,000 deaths per year or 1000 deaths per day in the United States. Sudden cardiac death occurs most commonly in patients with ischemic heart disease and primary myocardial disease associated with LV dysfunction, less commonly in those with WPW syndrome and mitral valve prolapse, and occasionally, in those without associated heart disease (e.g., Brugada syndrome). Patients who have sudden cardiac death (not associated with acute MI) but survive because of appropriate CPR often have inducible sustained ventricular tachycardia and/or ventricular fibrillation during electrophysiologic studies. These individuals are at high risk for the recurrence of ventricular tachycardia and/or ventricular fibrillation. 

The mechanism whereby cardiac glycosides cause a positive inotropic effect and electrophysiological changes is still not completely known despite years of active investigation. Several mechanisms have been proposed, but the most widely accepted mechanism involves the ability of cardiac glycosides to inhibit the membrane-bound Na /K -adenosine triphosphatase (Na /K -ATPase) pump responsible for sodium/potassium exchange. To understand better the correlation between the pump and the mechanism of action of cardiac glycosides on the heart muscle contraction, one has to consider the sequence of events associated with cardiac action potential that ultimately leads to muscular contraction. The process of membrane depolarization/repolarization is controlled mainly by the movement of the three ions, Na", K", Ca ", in and out of the cell. 

Cardiovascular Intravenous procainamide had a prodysrhythmic effect when it was given as a single 1000 mg bolus during an electrophysiological study in a patient with myotonic dystrophy type 1 [SO J. During ventricular pacing, ventricular tachycardia and fibrillation occurred and required DC cardioversion. By slowing cardiac conduction, procainamide, as do other sodium channel blockers, worsens abnormalities already present in the hearts of patients with myotonic dystrophy t)q)e 1. 

Indoramine (XII, Wy 21901) abolishes epinephrine- and ouabain-induced cardiac arrythmias by a combination of a-adrenoreceptor blockade and membrane stabilization. These effects have also been studied electrophysiologically. Indoramine has a pA2 of 7 as a competitive a-blocker on aortic strip, and a pA2 of 8.2 as an antihistamine on guinea pig ileum.The blood pressure of cats and conscious renal hypertensive rats is lowered by indoramine at 20-40 mg/kg (p.o.) several analogs are also active but rather toxic.50 a dose-related reduction in blood pressure accompanied by an increase in heart rate after administration of indoramine has been observed in man.51... 

Electrophysiology and pharmacology of cardiac arrhythmias. IV. Cardiac antiarrhythmic and toxic effects of digitalis. Amer. Heart J., 89, 391. 

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