Purkinje fiber

Purity ofthe sugar Purkinje fibers Purolite... 

Automa-ticity. Special cardiac cells, such as SA and AV nodal cells, His-bundle cells, and Purkinje fibers, spontaneously generate an impulse. This is the property of automaticity. Ectopic sites can act as pacemakers if the rate of phase 4 depolarization or resting membrane potential is increased, or the threshold for excitation is reduced. 

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... 

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

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. 

Purkinje fibers Specialized myocardial fibers that conduct impulses from the atrioventricular node to the ventricles. 

Describe the mechanism and physiological significance of rapid electrical conduction through the Purkinje fibers... 

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.

The final portion of the specialized conduction system consists of the Purkinje fibers that extend from the bundle branches. These fibers, which... 

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. 

It is customary today to classify anti arrhythmic drugs according to their mechanism of action. This is best defined by intracellular recordings that yield monophasic action potentials. In the accompanying figure, the monophasic action potentials of (A) slow response fiber (SA node) and (B) fast Purkinje fiber are shown. For each description that follows, choose the appropriate drug with which the change in character of the monophasic action potential is likely to be associated... 

Isolated ventricular Purkinje fibers from dog or sheep. 

Cardiac Action Potential In Vitro Purkinje Fibers. Intracellular recording of action potentials from cardiac Purkinje fibers isolated from dog or sheep ventricle. Measurement of maximum rate of depolarization and action potential duration to detect sodium and potassium channel interactions, respectively, according to recommendations in EM A CPMP Points to Consider document, CPMP 986/96 (1998). 

Purkinje fibers Papillary muscle Isolated cardiac myocytes... 

Recently, Bottino et al. [151] developed mathematical models that use hERG IC50 data and APD results measured from dog Purkinje fibers to predict drug interaction with other cardiac ion currents and dispersion of repolarization in transmural ECG. As regards cardiac Purkinje cells, a recent study suggested that rabbit cells might be more suitable for screening purposes because they possess a lower repolarization reserve than canine cells [152]. 

To ascertain the effects of non-hERG-mediated QT prolongation, test key compounds in relevant ex vivo (e.g. Langendorff [38], dog purkinje fibers [39]) or in vivo [40] models as early as possible. 

Gintant, G.A., Limberis, J.T., McDermott, J.S., Wegner, C.D. and Cox, B.F. (2001) The canine purkinje fiber an in vitro model system for acquired long QT syndrome and drug-induced arrhythmogenesis. Journal of Cardiovascular Pharmacology, 37, 607-618. 

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... 

Pharmacology Therapeutic concentrations of lidocaine attenuate phase 4 diastolic depolarization, decrease automaticity and cause a decrease or no change in excitability and membrane responsiveness. Action potential duration and effective refractory period (ERP) of Purkinje fibers and ventricular muscle are decreased, while the ratio of ERP to action potential duration is increased. Lidocaine raises ventricular fibrillation threshold. AV nodal conduction time is unchanged or shortened. Lidocaine increases the electrical stimulation threshold of the ventricle during diastole. 

Mechanism - Structurally like lidocaine, mexiletine inhibits the inward sodium current, thus reducing the rate of rise of the action potential. Phase 0. Mexiletine decreases the effective refractory period (ERP) in Purkinje fibers. The decrease in ERP is of lesser magnitude than the decrease in action potential duration (APD), with a resulting increase in ERP/APD ratio. 

A. Class la Lengthens duration of action potential (t the refractory period in atrial and ventricular muscle, in SA and AV conduction systems, and Purkinje fibers)... 

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]. 

The antiarrhythmic drugs in class I suppress both normal Purkinje fiber and His bundle automaticity in addition to abnormal automaticity resulting from myocardial damage. Suppression of abnormal automaticity permits the sinoatrial node again to assume the role of the dominant pacemaker. 

Members of class IB have a minimal effect on the rate of depolarization and are characterized by their ability to decrease the duration of action potential and ERP of Purkinje fibers. Members of this class have a minimal effect on conduction velocity in ventricular myocardium and are without apparent effect on refractoriness. 

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