Cardiac conduction system potentials

Figure 4.11. Generation of spontaneous action potentials in the cardiac conduction system. Depolarization starts as a slowly ascending prepotential that is due to the Caj. channel. Once the corresponding threshold is reached, the Ca channel opens, and the action potential is triggered. It is terminated by inactivation of the Ca chaimels, and by the opening of Ky chaimels (which have the same role here as in the skeletal muscle and nerves).

The cardiac cycle is tightly controlled by the cardiac conducting system, which initiates electrical impulses and carries them, via a specialized conducting system, to the myocardium. The surface electrocardiogram (EGG) records changes in potential and is a graphic tracing of the variations in electrical potential caused by the excitation of the heart muscle and detected at the body surface. Clinically, the EGG is used to identify (1) anatomic, (2) metabolic, (3)... 

Stimulation or inhibition of autonomic effector cells by ACh results from interaction of ACh with muscarinic ACh receptors. In this case, the effector is coupled to the receptor by a G protein (see Chapter 1). In contrast to skeletal muscle and neurons, smooth muscle and the cardiac conduction system (sinoatrial [SA] node, atrium, atrioventricular [AV] node, and the His-Purkinje system) normally exhibit intrinsic activity, both electrical and mechanical, that is modulated but not initiated by nerve impulses. At some smooth muscle, ACh causes a decrease in the resting potential (i.e., the membrane potential becomes less negative) and an increase in the frequency of spike production, accompanied by a rise in tension. A primary action of ACh in initiating these effects through muscarinic receptors is probably partial depolarization of the cell membrane brought about by an increase in Na and, in some instances, Ca conductance activation of muscarinic receptors can also activate the G -PLC-IP pathway leading to the mobilization of stored Ccf. Hence, ACh stimulates ion fluxes across membranes and/or mobilizes intracellular Ca to cause contraction. 

FIGURE 19.2 Cardiac action potential. Computed with the DiFrancesco-Noble membrane model for the cardiac conduction system (membrane patch). B, baseline E, excitation R, recovery (repolarization). 

As with the normal cardiac conducting system and its propagation of impulses through the His Purkinje network, electrostimulation by an artificial cardiac pacemaker depends on the depolarization of a single or a group of myocyte cell membranes which can then act as pacemaker cells. In order for these cells to depolarize, the electric field of the applied artificial pacemaker stimulus must exceed a threshold voltage. This initiates a complex cascade of ionic currents both in and out of the cell membrane referred to as the action potential. The impulse or wave of depolarization then propagates away from the site of stimulation from cell to cell across gap junctions or intercalated disks, which with normal cells provide very low resistance to depolarization. 

Six helpful appendices are included Quick guide to cardiac arrhythmias summarizes the details of 20 arrhythmias Cardiac drug overview covers commonly used cardiac drugs Best monitoring leads shows the most beneficial leads to monitor for the most challenging arrhythmias Depolarization-repolarization cycle explains the five phases of this cardiac cycle Action potential curves reviews the cellular changes that occur during the depolarization-repolarization cycle and Cardiac conduction system reviews how electrical impulses affect heart function. 

General definitions relating to action potentials are given in Section 9. This section deals specifically with action potentials within the cardiac pacemaker cells and conducting system. 

Conduction system abnormalities are common in chronic heart failure, occurring in 15-30% of the population with low left ventricular ejection fraction (LVEF) [1-3]. The prevalence in ischemic heart disease is roughly similar to that seen in other forms of dilated cardiomyopathy. Conduction system disease can occur both at the time of an acute myocardial infarction as well as slowly progressing in chronic ischemic heart disease. Intraventricular conduction delays are associated with a poor prognosis in heart failure, with up to a 70% increase in the risk of death, and are also more prevalent in patients with advanced symptoms [2,4]. In ischemic heart disease, all components of the conduction system are at risk of ischemic injury, from the sinoatrial node to the His-Pukinje system. These conduction system abnormalities have the potential to impair cardiac function by a number of mechanisms. Since conduction abnormalities impair cardiac function, it is logical that pacing therapies to correct or improve these conduction abnormalities may improve cardiac function. 

The cardiac safety of nomlfensin was established by measurements of cardiac conduction in depressed patients receiving therapeutic doses over 3 weeks, and it was less toxic than doxepin or amitriptyline In Isolated hearts. 3 Nomlfensin Inhibited NA uptake in the same way as TCA but its principal actions may be on dopaminergic (DA) systems, both as an uptake inhibitor and as an agonist.5 The metabolites (, Ri=0H, R2=H 2c, Ri= OCH3, R2=0H Ri=0H, R2=OCH3) Inhibit the uptake of DA and 5-HT, but another potential metabolite, the catechol (2e, Rx=R2=0H) is a potent DA agonist in behavioral and neurochemical studies. 5 However, the beneficial effects of 7 in parkinsonism may be due to its improvement of depressive s3nnptoms. 6... 

The basic rhythm of heart rate is maintained by a part of the heart known as the pacemaker or sinoatrial (SA) node. This is a group of cardiac muscle cells in the right atrium that depolarize spontaneously. Depolarization of cardiac muscle cells brings about contraction. The pacemaker forms part of a conduction system that transmits electrical activity through the heart by means of action potentials so that contractions are coordinated and the heart can function as an efficient pump. The conduction pathway of electrical activity goes from the SA node to the atrioventricular (AV) node between atria and ventricles, then down the septum between the two ventricles to the apex of the heart and finally round the ventricles themselves. The conduction pathway in the heart is shown in Figure 4.2. 

Figure 24.7 shows an example of a His bundle recording. The top two traces are leads II and Vq of the EGG and the bottom trace is the voltage difference from two electrodes on the indwelling electrode catheter. This internal view of cardiac activation combined with the His bundle electrogram has been referred to as His bundle electrocardiography [20]. Atrial activation on the catheter recording is called the A deflection and ventricular activation called the V deflection. The His bundle potential is the central H deflection. Since the catheter is located very close to the His bundle and AV node, it is assumed that the A deflection arises from atrial muscle tissue close to the AV node. When combined with the surface lead information a number of new intervals can be obtained. These are the PA, AH, and HV intervals. The PA interval is a measure of atrial muscle activation time, the AH interval is a measure of AV nodal activation time, and the HV interval is a measure of the ventricular conduction system activation time. 

The electrocardiographic picture of excitatory processes in the heart recorded from the surface of the body results from the superposition of the potentials of individual cardiac fibres The amplitude and time parameters of the electrocardiographic potentials depend upon the amplitude, the sequence of the local waves of excitation and the velocity at which they travel along special conducting systems and the contractile heart musculature. 

Because of the potential arrythmogenic properties of clomipramine, it is usually not employed as a first-line agent in uncomplicated OCD. Its use mandates an evaluation of the pediatric patient s medical condition and cardiac status in particular. Baseline evaluation should include a systems review and inquiry regarding a personal or family history of heart disease. A history of nonfebrile seizures should also be noted but is not an absolute contraindication to clomipramine. If in doubt, a general pediatric examination to include auscultation of the heart and measurement of pulse and blood pressure is indicated. A baseline (pretreatment) electrocardiogram (EKG) should be requested. While changes in conduction intervals and heart rate may occur, these are rarely of clinical significance. The prudent practitioner will evaluate and document EKG parameters. 

Cardiovascular System. Atropine is sometimes used to block the effects of the vagus nerve (cranial nerve X) on the myocardium. Release of acetylcholine from vagal efferent fibers slows heart rate and the conduction of the cardiac action potential throughout the myocardium. Atropine reverses the effects of excessive vagal discharge and is used to treat the symptomatic bradycardia that may accompany myocardial infarction.4 Atropine may also be useful in treating other cardiac arrhythmias such as atrioventricular nodal block and ventricular asystole. 

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