Sinoatrial node, conduction

Cyclic nucleotide-modulated ion channels (Table 6-2) are not K+-selective. Nevertheless, their inward current of Na+ and Ca2+ ions is conducted through a channel that is similar in overall architecture to Shaker K+ channels. This protein family includes the CNG channels, which respond only to cyclic nucleotides, and the HCN channels, which are activated synergistically by hyperpolarization and cyclic nucleotide binding [38,40]. The CNG channels are involved in signaling of visual and olfactory information and serve as cyclic nucleotide-gated Ca2+ channels. In contrast, the HCN channels are required for normal rhythmic electrical discharges by the sinoatrial node in the heart and the pacemaker cells of the thalamus. 

This group consists of j3-adrenergic receptor blockers, the antiarrhythmic activity of which is associated with inhibition of adrenergic innervation action of the circulatory adrenaline on the heart. Because all 8-adrenoblockers reduce stimulatory sympathetic nerve impulses of catecholamines on the heart, reduce transmembrane sodium ion transport, and reduce the speed of conduction of excitation, sinoatrial node and contractibility of the myocardium is reduced, and automatism of sinus nodes is suppressed and atrial and ventricular tachyarrhythmia is inhibited. 

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. 

Transmembrane action potential of a sinoatrial node cell. In contrast to other cardiac cells, there is no phase 2 or plateau. The threshold potential (TP) is -40 mV. The maximum diastolic potential (MDP) is achieved as a result of a gradual decline in the potassium conductance (gK+). Spontaneous phase 4 or diastolic depolarization permits the cell to achieve the TR thereby initiating an action potential (g = transmembrane ion conductance). Stimulation of pacemaker cells within the sinoatrial node decreases the time required to achieve the TR whereas vagal stimulation and the release of acetylcholine decrease the slope of diastolic depolarization. Thus, the positive and negative chronotropic actions of sympathetic and parasympathetic nerve stimulation can be attributed to the effects of the respective neurotransmitters on ion conductance in pacemaker cells of the sinuatrial node. gNa+ = Na+ conductance. 

Myocytes within the sinoatrial node possess the most rapid intrinsic rate of automaticity therefore, the sinoatrial node serves as the normal pacemaker of the heart. Specialized cells within the atria, atrioventricular (A-V) node, and His-Purkinje system are capable of spontaneous depolarization, albeit at a slower rate. The more rapid rate of depolarization of the sinoatrial nodal cells normally suppresses all of the other cells with the potential for automaticity. The other cells will become pacemakers when their own intrinsic rate of depolarization becomes greater than that of the sinoatrial node or when the pacemaker cells within the sinoatrial node are depressed. When impulses fail to conduct across the A-V node to excite the ventricular myocardium (heart... 

II Propranolol Metoprolol Nadolol Acebutolol Atenolol Pindolol Timolol Sotalol EsmoloF 3-Adrenoceptor antagonist, cardiac membrane stabilization, indirect effect on sinoatrial node to decrease rate of spontaneous diastolic depolarization. Indirect effect on A-V node to decrease conduction velocity and prolong ERR... 

Historically and romantically, the heartbeat is recognized as the quintessential hallmark of life. Normally, the heart beats at 60-100 beats per minute (bpm), with each beat yielding a ventricular contraction that ejects blood out to the body. Each heartbeat is an electrical event that originates from a collection of electrically excitable cells within the heart called the sinoatrial node (SA), anatomically located at the upper pole of the heart. The sinoatrial node is the primary pacemaker of the heart. The electrical impulse generated in the sinoatrial node spreads rapidly downward from the atria chambers of the heart and reaches the atrioventricular node (AV), a collection of electrically excitable cells that constitutes the electrical interface between the atria and ventricles of the heart. Erom the AV node, the impulse propagates throughout the ventricles via an electrical conduction system referred to as the His-Purkinje system. The electrical transmission... 

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. 

Cardiac muscle is highly dependent on calcium influx for normal function. Impulse generation in the sinoatrial node and conduction in the atrioventricular node—so-called slow-response, or calcium-dependent, action potentials—may be reduced or blocked by all of the calcium channel blockers. Excitation-contraction coupling in all cardiac cells requires calcium influx, so these drugs reduce cardiac contractility in a dose-dependent fashion. In some cases, cardiac output may also decrease. This reduction in cardiac mechanical function is another mechanism by which the calcium channel blockers can reduce the oxygen requirement in patients with angina. 

Lidocaine is one of the least cardiotoxic of the currently used sodium channel blockers. Proarrhythmic effects, including sinoatrial node arrest, worsening of impaired conduction, and ventricular arrhythmias, are uncommon with lidocaine use. In large doses, especially in patients with preexisting heart failure, lidocaine may cause hypotension—partly by depressing myocardial contractility. 

Verapamil blocks both activated and inactivated L-type calcium channels. Thus, its effect is more marked in tissues that fire frequently, those that are less completely polarized at rest, and those in which activation depends exclusively on the calcium current, such as the sinoatrial and atrioventricular nodes. Atrioventricular nodal conduction time and effective refractory period are invariably prolonged by therapeutic concentrations. Verapamil usually slows the sinoatrial node by its direct action, but its hypotensive action may occasionally result in a small reflex increase of sinoatrial nodal rate. 

Adenosine is a nucleoside that occurs naturally throughout the body. Its half-life in the blood is less than 10 seconds. Its mechanism of action involves activation of an inward rectifier K+ current and inhibition of calcium current. The results of these actions are marked hyperpolarization and suppression of calcium-dependent action potentials. When given as a bolus dose, adenosine directly inhibits atrioventricular nodal conduction and increases the atrioventricular nodal refractory period but has lesser effects on the sinoatrial node. Adenosine is currently the drug of choice for prompt conversion of paroxysmal supraventricular tachycardia to sinus rhythm because of its high efficacy (90-95%) and very short duration of action. It is usually given in a bolus dose of 6 mg followed, if necessary, by a dose of 12 mg. An uncommon variant of ventricular tachycardia is adenosine-sensitive. The drug is less effective in the presence of adenosine receptor blockers such as theophylline or caffeine, and its effects are potentiated by adenosine uptake inhibitors such as dipyridamole. 

FIGURE 23-2 Schematic representation of the conduction system of the heart. Conduction normally follows the pathways indicated by the dashed lines. Impulses originate in the sinoatrial node and are transmitted to the atrioventricular node. Impulses are then conducted from the atrioventricular node to the ventricles by the bundle of His and bundle branches. 

Schematic representation of the heart and normal cardiac electrical activity (intracellular recordings from areas indicated and ECG). Sinoatrial node, atrioventricular node, and Purkinje cells display pacemaker activity (phase 4 depolarization). The ECG is the body surface manifestation of the depolarization and repolarization waves of the heart. The P wave is generated by atrial depolarization, the QRS by ventricular muscle depolarization, and the T wave by ventricular repolarization. Thus, the PR interval is a measure of conduction time from atrium to ventricle, and the QRS duration indicates the time required for all of the ventricular cells to be activated (ie, the intraventricular conduction time). The QT interval reflects the duration of the ventricular action potential.

Figure 5.8. The conduction system of the heart, a Anatomy, b Electrical rhythm in the sinoatrial node (top), atrioventricular node (center), and the heart muscle (bottom). The dotted line inb (center) represents the own rhythm of the AV node that normally gets overridden by the faster sinoatrial rhythm (solid line).

It has long been believed that cardiac arrhythmias result from changes in the conducting properties and/or automaticity of the myocardium. Normally, each cardiac impulse arises in the sinoatrial node in the right atrium and then is rapidly transmitted throughout the atria and via the atrioventricular node, His bundle, bundle branches and specialized conduction fibers (Purkinje fibers) to all regions of the ventricles to assure coordinated activation and contraction. 

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