Heart refractory period

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). 

The electrophysiological effects of amiodarone may be a composite of several properties. In addition to prolonging action potential duration and refractory period in ad tissues of the heart, the compound is an effective sodium channel blocker (49), calcium channel blocker (50), and a weak noncompetitive -adrenoceptor blocking agent (51). Amiodarone slows the sinus rate, markedly prolongs the QT interval, and slightly prolongs the QRS duration (1,2). 

Sympathetic (sympatholytic) Heart Sinus node Atrioventricular (AV node) Slowing Increased refractory period Bradycardia Dysrhythmias, conduction block... 

Procainamide (Class IA antiarrhythmic drug) is an effective agent for ventricular tachycardia. Its mechanism of action involves blockade of the fast Na+ channels responsible for phase 0 in the fast response tissue of the ventricles. Therefore, its effect is most pronounced in the Purkinje fibers. The effects of this drug s activity include a decrease in excitability of myocardial cells and in conduction velocity. Therefore, a decrease in the rate of the phase 0 upstroke and a prolonged repolarization are observed. As a result, duration of the action potential and the associated refractory period is prolonged and the heart rate is reduced. These effects are illustrated by an increase in the duration of the QRS complex. 

The quinolinone derivative, OPC-88117 (73), is yet another compound described as possessing both Class I and Class III electrophysiological activities. Studies in guinea-pig papillary muscle showed that OPC-88117 at 30 increased APDgo by about 15% and decreased F ,ax by only 4% however, at 100 /iM APDgo was prolonged by 23 % and was decreased by 23 % [206]. Further experiments in isolated rabbit hearts demonstrated that OPC-88117 increased atrio-His bundle (A-H) and His bundle-ventricle (H-V) conduction times and refractory periods with a profile that was similar to, but more potent than that of lidocaine [207]. 

Drugs used for treating arrhythmia can have an effect on the electrical conduction system of the heart, its excitability, automatism, the size of the effective refractory period, and adrenergic and cholinergic heart innervation. Accordingly, compounds of various chemical classes can restore heart rate disturbances. 

Propranolol slows heart rate, increases the effective refractory period of atrioventricular ganglia, suppresses automatism of heart cells, and reduces excitability and contractibihty of the myocardium. It is used for supraventricular and ventricular arrhythmias. Synonyms of this drug are anaprilin, detensiel, inderal, novapranol, and others. 

Pharmacology Procainamide, a class lA antiarrhythmic, increases the effective refractory period of the atria, and to a lesser extent the bundle of His-Purkinje system and ventricles of the heart. 

Ibutilide causes an increase in the atrial refractory period, an effect seen at rapid heart rates. 

The answer is c. (Hardman, pp 813-814.) Digoxin is used in AF to slow the ventricular rate, not usually the AF itself. Digoxin acts to slow the speed of conduction, increase the atrial and AV nodal maximal diastolic resting membrane potential, and increase the effective refractory period in the AV node, which prevents transmission of all impulses from the atria to the ventricles. It exerts these effects by acting directly on the heart and by indirectly increasing vagal activity. 

Atropine initially decrease the heart rate due to stimulation of vagal centre followed by tachycardia due to peripheral vagal block on SA node. It also shortens effective refractory period of AV node and facilitates AV conduction. In therapeutic doses, atropine completely blocks the peripheral vasodilatation and decrease in blood pressure produced by cholinergic agents. 

Direct effects on the heart are determined largely by Bi receptors, although B2 and to a lesser extent a receptors are also involved, especially in heart failure. Beta-receptor activation results in increased calcium influx in cardiac cells. This has both electrical and mechanical consequences. Pacemaker activity—both normal (sinoatrial node) and abnormal (eg, Purkinje fibers)—is increased (positive chronotropic effect). Conduction velocity in the atrioventricular node is increased (positive dromotropic effect), and the refractory period is decreased. Intrinsic contractility is increased (positive inotropic effect), and relaxation is accelerated. As a result, the twitch response of isolated cardiac muscle is increased in tension but abbreviated in duration. In the intact heart, intraventricular pressure rises and falls more rapidly, and ejection time is decreased. These direct effects are easily demonstrated in the absence of reflexes evoked by changes in blood pressure, eg, in isolated myocardial preparations and in patients with ganglionic blockade. In the presence of normal reflex activity, the direct effects on heart rate may be dominated by a reflex response to blood pressure changes. Physiologic stimulation of the heart by catecholamines tends to increase coronary blood flow. 

Arrhythmias are caused by abnormal pacemaker activity or abnormal impulse propagation. Thus, the aim of therapy of the arrhythmias is to reduce ectopic pacemaker activity and modify conduction or refractoriness in reentry circuits to disable circus movement. The major mechanisms currently available for accomplishing these goals are (1) sodium channel blockade, (2) blockade of sympathetic autonomic effects in the heart, (3) prolongation of the effective refractory period, and (4) calcium channel blockade. 

The excitable membrane of nerve axons, like the membrane of cardiac muscle (see Chapter 14) and neuronal cell bodies (see Chapter 21), maintains a resting transmembrane potential of -90 to -60 mV. During excitation, the sodium channels open, and a fast inward sodium current quickly depolarizes the membrane toward the sodium equilibrium potential (+40 mV). As a result of this depolarization process, the sodium channels close (inactivate) and potassium channels open. The outward flow of potassium repolarizes the membrane toward the potassium equilibrium potential (about -95 mV) repolarization returns the sodium channels to the rested state with a characteristic recovery time that determines the refractory period. The transmembrane ionic gradients are maintained by the sodium pump. These ionic fluxes are similar to, but simpler than, those in heart muscle, and local anesthetics have similar effects in both tissues. 

Bayer BL, Forster W Actions of prostaglandin precursors and other unsaturated fatty acids on conduction time and refractory period in the cat heart. Br J Pharmacol 1979 66 191-195. 

Drugs that block beta-1 receptors on the myocardium are one of the mainstays in arrhythmia treatment. Beta blockers are effective because they decrease the excitatory effects of the sympathetic nervous system and related catecholamines (norepinephrine and epinephrine) on the heart.5,28 This effect typically decreases cardiac automaticity and prolongs the effective refractory period, thus slowing heart rate.5 Beta blockers also slow down conduction through the myocardium, and are especially useful in controlling function of the atrioventricular node.21 Hence, these drugs are most effective in treating atrial tachycardias such as atrial fibrillation.23 Some ventricular arrhythmias may also respond to treatment with beta blockers. 

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