Initiation & Conduction of the Cardiac Impulse

INITIATION & CONDUCTION OF THE CARDIAC IMPULSE

The cardiac impulse normally originates in the sino-atrial (SA) node, a group of specialized pacemaker cells in the sulcus terminalis, located posteriorly at the junction of the right atrium and the superior vena cava. These cells seem to have an outer mem-brane that leaks Na ⁺ (and possibly Ca²⁺). The slow influx of Na⁺, which results in a less negative rest-ing membrane potential (–50 to –60 mV), has three important consequences: near constant inactivation of voltage-gated sodium channels, an action poten-tial with a threshold of –40 mV that is primarily due to ion movement across the slow calcium channels, and regular spontaneous depolarizations. During each cycle, intracellular leakage of Na ⁺ causes the cell membrane to become progressively less nega-tive; when the threshold potential is reached, cal-cium channels open, K⁺ permeability decreases, and an action potential develops. Restoration of normal K⁺ permeability returns the cells in the SA node to their normal resting membrane potential.

The impulse generated at the SA node is nor-mally rapidly conducted across the atria and to the AV node. Specialized atrial fibers may speed up conduction to both the left atrium and the AV node. The AV node, which is located in the septal wall of the right atrium, just anterior to the opening of the coronary sinus and above the insertion of the septal leaflet of the tricuspid valve, is actually made up of three distinct areas: an upper junctional (AN) region, a middle nodal (N) region, and a lower junc-tional (NH) region. Although the N region does not possess intrinsic spontaneous activity (automatic-ity), both junctional areas do. The normally slower rate of spontaneous depolarization in AV junctional areas (40–60 times/min) allows the faster SA node to control heart rate. Any factor that decreases the rate of SA node depolarization or increases the auto-maticity of AV junctional areas allows the junctional areas to function as the pacemaker for the heart.

Impulses from the SA node normally reach the AV node aft er about 0.04 sec, but leave after another 0.11 sec. This delay is the result of the slowly con-ducting small myocardial fibers within the AV node, which depend on slow calcium channels for propa-gation of the action potential. In contrast, conduc-tion of the impulse between adjoining cells in the atria and in the ventricles is due primarily to activa-tion of sodium channels. The lower fibers of the AV node combine to form the common bundle of His. This specialized group of fibers passes into th interventricular septum before dividing into left and right branches to form the complex network of Pur-kinje fibers that depolarizes both ventricles. In sharp contrast to AV nodal tissue, His–Purkinje fibers have the fastest conduction velocities in the heart, resulting in nearly simultaneous depolarization of the entire endocardium of both ventricles (normally within 0.03 s). Synchronized depolarization of the lateral and septal walls of the left ventricle promotes effective ventricular contraction. The spread of the impulse from the endocardium to the epicardium through ventricular muscle requires an additional 0.03 sec. Thus, an impulse arising from the SA node normally requires less than 0.2 sec to depolarize the entire heart.

Potent inhaled anesthetics depress SA node automaticity. These agents seem to have onlymodest direct effects on the AV node, prolonging conduction time and increasing refractoriness. This combination of effects likely explains the occur-rence of junctional tachycardia when an anticholin-ergic is administered for sinus bradycardia during inhalation anesthesia; junctional pacemakers are accelerated more than those in the SA node. The electrophysiological effects of volatile agents on Pur-kinje fibers and ventricular muscle are complex due to autonomic interactions. Both antiarrhythmic and arrhythmogenic properties are described. The for-mer may be due to direct depression of Ca²⁺ influxes,whereas the latter generally involves potentiation of catecholamines, especially with halothane. The arrhythmogenic effect requires activation of both α₁- and β-adrenergic receptors. Intravenous induc-tion agents have limited electrophysiological effects in usual clinical doses. Opioids, particularly fentanyl and sufentanil, can depress cardiac conduction, increasing AV node conduction and the refractory period and prolonging the duration of the Purkinje fiber action potential.

Local anesthetics have important electrophysi-ological effects on the heart at blood concentrations that are generally associated with systemic toxicity. In the case of lidocaine, electrophysiological effects at low blood concentrations can be therapeutic. At high blood concentrations, local anesthetics depress con-duction by binding to sodium channels; at extremely high concentrations, they also depress the SA node. The most potent local anesthetics—bupivacaine, eti-docaine, and to a lesser degree, ropivacaine—seem to have the most potent effects on the heart, particu-larly on Purkinje fibers and ventricular muscle. Bupi-vacaine binds open or inactivated sodium channels and dissociates from them slowly. It can cause pro-found sinus bradycardia and sinus node arrest and malignant ventricular arrhythmias; furthermore, it can depress left ventricular contractility. Twenty percent lipid emulsions have been used to treat local anesthetic cardiac toxicity. The mechanisms of action of this therapy are unclear, although possibilities include serving as a lipid reservoir and decreasing lipophilic toxic local anesthetics in the myocardium.

Calcium channel blockers are organic com-pounds that block Ca²⁺ influx through L-type but not T-type channels. Dihydropyridine blockers, such as nifedipine, simply plug the channel, whereas other agents, such as verapamil, and to a lesser extent, dil-tiazem, preferentially bind the channel in its depo-larized inactivated state (use-dependent blockade).