Heart Purkinje fibers

Sheep heart Purkinje fibers closed end, recessed up—all-glass microelectrode Na- 7.3mM 147)... 

The Cardiac Cycle. The heart (Eig. lb) performs its function as a pump as a result of a rhythmical spread of a wave of excitation (depolarization) that excites the atrial and ventricular muscle masses to contract sequentially. Maximum pump efficiency occurs when the atrial or ventricular muscle masses contract synchronously (see Eig. 1). The wave of excitation begins with the generation of electrical impulses within the SA node and spreads through the atria. The SA node is referred to as the pacemaker of the heart and exhibits automaticity, ie, it depolarizes and repolarizes spontaneously. The wave then excites sequentially the AV node the bundle of His, ie, the penetrating portion of the AV node the bundle branches, ie, the branching portions of the AV node the terminal Purkinje fibers and finally the ventricular myocardium. After the wave of excitation depolarizes these various stmetures of the heart, repolarization occurs so that each of the stmetures is ready for the next wave of excitation. Until repolarization occurs the stmetures are said to be refractory to excitation. During repolarization of the atria and ventricles, the muscles relax, allowing the chambers of the heart to fill with blood that is to be expelled with the next wave of excitation and resultant contraction. This process repeats itself 60—100 times or beats per minute... 

The cardiotonics affect the transmission of electrical impulses along the pathway of the conduction system of tiie heart. The conduction system of die heart is a group of specialized nerve fibers consisting of die SA node, die AV node, the bundle of His, and die branches of Purkinje (Fig. 39-2). Each heartbeat (or contraction of tiie ventricles) is tiie result of an electrical impulse tiiat normally starts in tiie SA node, is tiien received by die AV node, and travels down die bundle of His and through tiie Purkinje fibers (see Fig. 39-2). The heartbeat can be felt as a pulse at the wrist and otiier areas of die body where an artery is close to the surface or lies near a bone When the electrical impulse reaches the... 

Abnormal initiation of electrical impulses occurs as a result of abnormal automaticity. If the automaticity of the SA node increases, this results in an increased rate of generation of impulses and a rapid heart rate (sinus tachycardia). If other cardiac fibers become abnormally automatic, such that the rate of initiation of spontaneous impulses exceeds that of the SA node, other types of tachyarrhythmias may occur. Many cardiac fibers possess the capability for automaticity, including the atrial tissue, the AV node, the Purkinje fibers, and the ventricular tissue. In addition, fibers with the capability of initiating and conducting electrical impulses are present in the pulmonary veins. Abnormal atrial automaticity may result in premature atrial contractions or may precipitate atrial tachycardia or atrial fibrillation (AF) abnormal AV nodal automaticity may result in junctional tachycardia (the AV node is also sometimes referred to as the AV junction). Abnormal automaticity in the ventricles may result in ventricular premature depolarizations (VPDs) or may precipitate ventricular tachycardia (VT) or ventricular fibrillation (VF). In addition, abnormal automaticity originating from the pulmonary veins is a precipitant of AF. 

Figure 13.3 Route of excitation and conduction in the heart. The heart beat is initiated in the sinoatrial (SA) node, or the pacemaker, in the right atrium of the heart. The electrical impulse is transmitted to the left atrium through the interatrial conduction pathway and to the atrioventricular (AV) node through the intemodal pathway. From the AV node, the electrical impulse enters the ventricles and is conducted through the AV bundle, the left and right bundle branches, and, finally, the Purkinje fibers, which terminate on the true cardiac muscle cells of the ventricles.

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 electrical impulse for contraction (propagated action potential p. 136) originates in pacemaker cells of the sinoatrial node and spreads through the atria, atrioventricular (AV) node, and adjoining parts of the His-Purkinje fiber system to the ventricles (A). Irregularities of heart rhythm can interfere dangerously with cardiac pumping func-tioa... 

C. Class Ic Greater sodium current depression (blocks the fast inward Na current in heart muscle and Purkinje fibers, and slows the rate of t of phase 0 of the action potential)... 

A next-level assay is usually an isolated heart/cardiac tissue preparation. The canine Purkinje fiber assay (GLP) measures several action potential parameters, like resting membrane potential, upstroke velocity, action potential duration and shape, but also if a drug acts reverse-use dependently [72]. Based on changes of the action potential shape it is possible to conclude which ion channels are modulated (e.g., L-type calcium channel block would abolish the plateau phase). The papillary muscle assay (e.g., guinea pigs) determines similar parameters [73]. 

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. 

Cx40 was found in sinus node cells, atrium, AV node, AV bundle and bundle branches and Purkinje fibers. Cx45 was expressed at low levels in Purkinje fibers and ventricles of the canine heart [Kanter et al., 1993a, b, ]. 

Purkinje fibers obtained from 4 different dogs isolated from dog hearts and placed in a recording chamber and perfused with Tyrode s solution at... 

Purkinje fibers are excised from the isolated heart and placed in a superfusion chamber with warmed (37 °C) Tyrode s solution containing 4mM potassium and a flow rate of 8-10ml/min. The fibers are stimulated using platinum electrodes at 2 times threshold for 1-2 ms using a biphasic wave form. The fibers are then... 

CRITICAL ASSESSMENT OF THE METHOD The Purkinje fiber is a non-contractile tissue, which facilitates electrode positioning and stability. In comparison to the papillary muscle or the monophasic action potential in the intact heart, drug-induced effects on the action potential duration are considerably larger. Whereas this is not necessarily a disadvantage, the model has been viewed as possibly being too sensitive for drug-induced effects on repolarization. 

The heart is mediated by an electrical system that is easily disturbed by toxicants changing the timing, flow, and magnitude of the electrical pulses and thus interfering with the required pumping action. The activity of the heart is myogenic, i.e. the activity is initiated by the heart itself Various components of the heart, the sinoatrial (SA) node, atrioventricular (AV) node, and the Purkinje fibers are capable of pacemaker activity. Healthy atrial and ventricular tissue does not engage in pacemaker activity. The primary pacemaker is the SA node, but in diseased or affected states the secondary pacemakers take over. 

The sinoatrial node (SA), consisting of spindle-shaped cells, initiates the electrical activity of the heart. From its location in the right atrium in proximity to the superior vena cava, the electrical activity spreads to the atria whose cells are larger than those of the SA. The pulse from the atria spreads to the atrioventricular node (AV), the gateway to the ventricles. The atria and the ventricles are electrically isolated. The AV node also slows down the electrical activity giving the atria time to fill. The bundle of His is the upper end of the electrical path, which through the Purkinje fibers allows the electrical signal to activate the ventricles and thus to pump the blood. 

The heart depends on the synchronous integration of electrical impulse transmission and myocardial tissue rcsponsc to cany exit its function as a pump. When the impulse is released from the SA node, excitation of the heart tis.sue takes place in an orderly manner by a spread of the impulse ihmughout the specialised autontatic fibers in the atria, the AV node, and the Purkinje fiber network in the ventricles. This spreading of impulses produces a characteristic clectro-atdiographic pattern that cun be equated to predictable myo-caidial cell membrane potentials and Nu and K fluxes In and out of the cell. 

Mexiletine hydrochloride, like cla.ss I antiarrhythmic agents, blocks the fast Na channel in cardiac cells. It is especially effective on the Purkinje fibers in the heart. The drug increases the threshold of excitability of myocardial cells by reducing the rale of rise and amplitude of the action potential and decreases aulomaliciiy. 

The normal orderly sequence of events in cardiac contraction is initiated by a primary pacemaker, the sinoatrial (SA) node,21 which is located near the surface at the junction of the right atrium and the superior vena cava. One of its properties is automaticity. The normal firing frequency is 60-100 impulses/minute. The established rhythm is conducted to the atrioventricular (AV) node. This node serves to slow the beat somewhat so that atrial contraction can occur before the ventricle is stimulated. The AV node is in the septum (dividing wall) between the atria. The impulse is conducted from the AV node to a common bundle of fibers (Bundle of His) that cross the right atrium to the left ventricle. From there a division of fibers directs impulses along the septum dividing the ventricles, down to the lateral walls and the apex of the heart. The branching of the common bundle leads into the Purkinje fibers that innervate the heart musculature of the ventricles. 

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