Anatomy and Blood Supply

The AV system of specialized myocytes is the only muscular bridge through the insulating fibro-fatty tissue plane that separates the atrial myocardial masses from the ventricular myocardial masses. The AV system begins with the atrioventricular node at its atrial end. The compact node is recognizable, when seen in cross-sections, as a half-oval shaped structure adjacent to the central fibrous body in the young (Figure 40-1, A).¹⁸ With increasing age, the shape changes to become spindle-like.¹⁹ When traced inferiorly, toward the base of Koch’s triangle, the compact area diverges into two prongs, usually with the artery supplying the node running in between. The extent of the prongs varies from heart to heart; the right extension increases with age.²⁰ Interposing between the compact node and the working atrial myocardium is a zone of transitional cells. These cells are histologically distinct from the cells of the compact node as well as the working cells but are not insulated from the surrounding myocardium. They approach the compact node superiorly, inferiorly, and from the left and right sides of the atrial septum. In the vestibular area of the right atrium, an overlay of ordinary myocytes is present in the subendocardium from the atrial wall in front of the oval fossa that streams over the zone of transitional cells. The transitional cells, therefore, provide the crucial proximal bridge between the ordinary and the specialized myocardium. Fibro-fatty tissue increases with age in this region, and the transitional cell zone becomes wider.¹⁹ When the conduction system is traced into the penetrating bundle of His, little difference is seen in the cellular composition of the two areas (see Figure 40-1, B). The specialized myocardial cells themselves, however, become aligned in a more parallel fashion distally into the AV conduction bundle. The AV node, therefore, is an integral part of the atrial musculature (see Figure 40-1, A), in contrast to the atrioventricular bundle, which, in passing through the central fibrous body, is insulated from the adjacent myocardium (see Figure 40-1, B). The His bundle, approximately 2 mm in cross-sectional diameter, is the only bridge of myocardial continuity between the atria and the ventricles. The common AV bundle and its continuation, the branching bundle, and bundle branches are also ensheathed in fibrous tissue. In the normal heart, the AV-branching bundle is sandwiched between the membranous septum and the muscular ventricular septum, usually a little to the left of the septal crest, giving origin to the left and right bundle branches (see Figures 40-1, C to E). The AV bundle lies in the subendocardium of the left ventricle beneath the commissure between the right-coronary and noncoronary leaflets of the aortic valve. In most hearts, the right bundle branch passes through the septal crest to emerge subendocardially in the septal aspect of the right ventricle (see Figure 40-1, E). Distally, the bundle branches divide into increasingly finer branches. Eventually, they ramify into the so-called Purkinje network and lose the fibrous sheaths at the interface with the ordinary ventricular myocardium.¹⁸

Figure 40-1 Histologic sections from children showing the normal configuration of the atrioventricular (AV) node (A), penetrating bundle of His (B), branching AV bundle (C), left bundle branch (D), and right bundle branch (E). All the sections are perpendicular to the plane of the cardiac septum with the left heart displayed superiorly and right heart inferiorly. Asterisks mark the conduction tissues. trs, Zone of transitional cells (trichrome stain: myocardium in red; fibrous tissue in green-blue).

Most frequently, the arterial supply to the AV node is a branch from the right coronary artery, whereas it is a branch from the circumflex artery in nearly 20%. When the dominant right coronary artery extends beyond the cardiac crux, the nodal artery originates distal to the U loop of the dominant artery.^20,21 In most hearts, the penetrating bundle and AV conduction bundle are supplied by a branch from the posterior descending coronary artery. The right bundle branch is supplied by the first septal perforating artery arising from the anterior descending coronary artery, which also supplies the AV conduction bundle in some hearts.^22,23

Acquired Complete Atrioventricular Block

Complete AV block can be categorized into four major pathologic groups and a further group with miscellaneous conditions.³⁷ An autopsy series of hearts from 200 patients who had AV block of more than 1-month duration found idiopathic bilateral bundle branch fibrosis in 38%, coronary artery disease in 17.5%, cardiomyopathy in 13%, calcific AV block in 11%, and other causes in 20.5%.³⁷

Idiopathic Bilateral Bundle Branch Fibrosis

The crest of the muscular ventricular septum undergoes degenerative changes, including fibrosis, fatty infiltration, and focal microscopic dystrophic calcification with advancing age. The normal aging process begins in the fourth decade of life but may be accelerated by coronary artery disease, diabetes mellitus, and hypertensive heart disease. Since the branching AV bundle and the beginning of the main bundle branches are located in this area, they are susceptible to being disrupted (Figure 40-3). Two forms of bundle branch fibrosis, focal and diffuse—dubbed Lev disease and Lenègres disease, respectively—are recognized, but they probably represent extreme ends of a pathologic spectrum.^38,39 In both groups the mean ages are reported to be in the sixth and seventh decades. Damage to the distal branches is minimal in the focal form, whereas damage in the diffuse form can extend to the middle and distal portions of both left and right bundle branches.

Figure 40-3 Histologic sections from a young adult showing loss of more conduction tissues than anticipated. A, Deficient atrial input to the atrioventricular node (asterisk). B, A narrow origin of the left bundle branch and loss of continuity (open arrow) with the branching bundle [trichrome stain: myocardium in red; fibrous tissue in green-blue].

Surgical and Interventional

Complete AV block may be a consequence of interventional procedures to correct congenital heart malformation. Damage may be caused by sutures or incisions into the musculature containing the conduction bundles, AV node, or their arterial supply. Although surgically induced iatrogenic block is rare nowadays, the shift toward trans-catheter device closure for ventricular septal defects has again put the spotlight on the potential risk to the AV conduction system.^47,48 AV block may also be a complication following isolated myectomy or alcohol ablation for hypertrophic obstructive cardiomyopathy.^49,50

The Compact Atrioventricular Node

Within the central compact node are cells with distinct electrophysiological characteristics. These characteristics of the prototypical AV nodal cells manifested by intracellular recordings in multicellular preparations have been replicated in cells isolated from the AV node, allowing determination of the activities of specific currents, pumps, and exchangers.^52,53 The amplitudes of resting potentials (–60 mV), APs (–85 mV), and upstroke velocities (<10 V/sec) are reduced. These cells manifest diastolic depolarization, a high total transmembrane (input) resistance, and relative insensitivity to changes in extracellular K⁺. They have post-repolarization refractoriness; the absolute refractory period outlasts the AP. The relative refractory period, during which relatively diminished, more slowly conducting APs are generated, is prolonged well into diastole. The amplitudes and upstroke velocities of APs and conduction velocity are strongly modulated by autonomic activity, increasing with adrenergic (sympathetic) stimulation and decreasing with cholinergic (vagal) stimulation. The AV junction is richly innervated with vagal and sympathetic fibers, but recent observations with high-resolution staining for neural tissues indicate that innervation of the compact node may be more sparse than that of the transitional fibers or the nodal extensions.^53,54

Important features of the transmembrane potentials can be explained by the array and activities of specific ionic currents. Like sinoatrial nodal cells, AV nodal cells lack the ionic current I_K1. These potassium ion (K⁺) channels in atrial and ventricular cells are open at strongly negative membrane potentials, providing the dominant K⁺ permeability that maintains the transmembrane potential near the K⁺ equilibrium potential. The absence of these channels in AV nodal cells is responsible for the relatively reduced resting potential positive to the K⁺ equilibrium potential, the insensitivity to extracellular K⁺ concentration, and the high membrane resistance of these cells.

AV nodal cells, like sinoatrial nodal cells, lack sodium (Na⁺) channels, which provide the excitatory current for atrial and ventricular cells; some cells may have channels that are inactivated at the low resting potentials.^55,56 The excitatory current for AV nodal cells is I_CaL, a calcium current that generates a slow upstroke because it is slower and less intense than the Na⁺ current. L-type calcium ion (Ca²⁺) channels require a relatively long period to recover from inactivation, hence the post-repolarization refractoriness of the AV node. The potent actions of autonomic stimulation on AV nodal conduction are largely due to the modulation of I_CaL by adrenergic and cholinergic stimulation via specific receptors and transduction systems. This current is enhanced, and its kinetics of activation, inactivation, and recovery are accelerated by adrenergic stimulation; it is conversely affected by cholinergic stimulation.

T-type Ca²⁺ current (I_CaT) has been shown recently to be important in AV conduction in mice. Genetically modified mice lacking these channels manifest slow conduction within the AV node as well as reduced rates of AV nodal pacemakers.⁵⁷ A study has reported congenital heart block and sinus bradycardia in children exposed to maternal antibodies that reduce both L-type and T-type channels, indicating a possible role of T-type channels in human AV nodal conduction.⁵⁸

On the one hand, AV nodal cells contain the pacemaker current I_f, which may contribute to the automaticity of AV nodal cells. On the other hand, the current I_to, a rapidly activating and inactivating K⁺ current that produces the notch of the AP (phase I) and is prominent in atrial cells, is sparse or absent in AV nodal cells. The repolarizing K⁺ current I_Kr is present and probably a major factor in the repolarization of AV nodal cells. The repolarizing current I_Ks, a contributor to repolarization in atrial, ventricular, and His–Purkinje cells, appears to be absent in AV nodal cells.

Ca²⁺-activated K⁺ channels (K_Ca) have been demonstrated in the activation of K_Ca in human atrial myocytes and has been shown to increase the rate of AV nodal pacemakers and accelerate repolarization.^59,60

The K⁺ current I_Ach,Ado is prominent in sinoatrial nodal cells and atrial cells but not in ventricular cells. It is also present in AV nodal cells. Activation of this current by acetylcholine or adenosine drives the resting potential to more negative values, suppresses automaticity, and diminishes the AP, thus slowing AV conduction.

Gap junctions appear to be sparse and smaller in the central AV node than in the atrial and ventricular myocardium.⁶¹ The gap junctions in the node are composed predominantly of connexin40 rather than connexin43, which is dominant in the ventricular myocardium. The relatively poor intercellular communication in the AV node is probably the result of these gap junction properties as well as a relative increase in the volume of extracellular space surrounding AV nodal cells, compared with the atrial and ventricular myocardium.