B. H. Neely

Quantitative effects of sympathetic and vagal nerve stimulations on sinus and AV junctional rhythms

Responses of the sinus node and atrioventricular (AV) junctional pacemakers to autonomic denervation and to individual stimulations of the right and left stellate and both vagi were studied in 33 anesthetized dogs. Autonomic denervation depressed sinus node automaticity by only 18% from control, whilst AV junctional automaticity was reduced by 48.5% from control. Sympathetic and parasympathetic stimulation frequency-response curves (0.25, 0.5, 1, 2, 4, 8, 16 and 32 Hz) were obtained. In the sinus node the chronotropic responses to sympathetic stimulations reflect a bilaterally asymmetrical innervation with a right sided preponderance. In contrast, sinus slowing in response to either right or left vagal stimulations were indistinguishable when lower frequencies of stimulation were used. At 4 Hz and higher frequencies there is a right vagal preponderance. The AV junctional chronotropic responses suggest that this major subsidiary pacemaker receives a bilaterally symmetrical autonomic innervation. The chronotropic responses to individual nerve stimulations expressed as percent changes in sinus rate and AV junctional rate from their respective controls after autonomic denervation show that the AV junction is far more responsive than the sinus node to both sympathetic and parasympathetic stimulations. To allow for more meaningful comparisons the data were normalized using the respective maximum increase and maximum decrease of sinus node and AV junctional rates to left and right sympathetic and parasympathetic stimulations as the 100% reference. These normalized curves show that 50% of the maximal chronotropic responses were always achieved at a lower stimulus frequency in the AV junction than in the sinus node; shift of the AV junctional response curves to the left of the sinus node response curves by a 0.2 (sympathetic) and 0.3 (parasympathetic) log units was observed. These studies further showed that sympathetic activity in the AV junction is an absolute prerequisite to maintain regular AV junctional rhythms especially during the bradycardic episodes evoked in the study of vagal stimulus frequency-response curves.

Differences in the determinants of overdrive suppression between sinus rhythm and slow atrioventricular junctional rhythm.

Sinus node recovery time was compared to the recovery time of a slow atrioventricular junctional rhythm in each of the same seven pentobarbital anesthetized dogs. Recovery time and the first five cardiac cycles were examined after pacing atria and ventricles for 20, 40, and 60 seconds at four or more pacing cycle lengths. Data relating recovery times and return to control conditions to prepacing cycle length, pacing cycle length, duration of pacing, site of pacing, and origin of rhythms were analyzed by covariance analysis. From the analyses, the relative contribution of the determinants are: the prepacing cycle length 73%, the site of paring 3.5%, the pacing cycle length 2%, and the interaction of the site of paring and paring cycle length 1% for sinus node recovery time; and for slow atrioventricular junctional rhythm recovery time, the duration of pacing 40%, the interactions between the duration of pacing and the pacing cycle length 27%, and the prepacing cycle length 9%. A modified exponential decay model predicted 8 beats for return to prepacing conditions during sinus rhythm and 66–100 beats during atrioventricular junctional rhythm. We conclude that the single most important determinant of sinus node recovery time is the prepacing cycle length. Pacing cycle length and site of pacing have a significant but small influence on sinus node recovery time and duration of paring, beyond 20 seconds, has no significant influence. In contrast, duration of paring is the most important determinant of slow atrioventricular junctional recovery time. Another major determinant of slow atrioventricular junctional recovery time is the interactions between pacing cycle length and duration of paring. Preparing cycle length has a minor influence, and site of pacing has no influence, on slow atrioventricular junctional recovery time.

Differential interaction of adrenergic and cholinergic effects on AV junctional automaticity and AV conduction

The effects of postsynaptic autonomic interactions on atrioventricular (AV) junctional automaticity and AV conduction were studied in six canine heart in situ using direct injections of norepinephrine (NE) and physostigmine (PSM) into the AV node artery. Injection of NE (0.05 microgram/ml, 2 ml) caused an AV junctional rhythm (AVJR) in every dog. After injection of PSM (10 micrograms/ml, 2 ml), the responses of AVJR to NE were virtually identical to those observed before cholinesterase inhibition (160 +/- 13 vs 162 +/- 12 bpm). In contrast, this moderate cholinesterase inhibition still had a readily demonstrable negative dromotropic effect. In any given dog, depressed AV conduction was characterized by one of two types (I and II) of retrograde atrial capture during AVJR. Before PSM in the AV junction, onset of atrial depolarization during AVJR preceded the onset of ventricular depolarization in both type I and type II responses. After PSM, atrial depolarization occurred later with respect to ventricular depolarization (i.e., during or mostly after ventricular activation) in type I, whereas in the type II responses atrial depolarizations began much earlier than before PSM, thus being completed long before the onset of ventricular activation. Because of such differential responsiveness of AV junctional automaticity and AV conduction and because of the two types of intranodal conduction observed after administration of PSM into the AV junction, we can postulate that under appropriate autonomic imbalance retrograde or antegrade AV block could readily develop in spite of preserved AV junctional automaticity.

Atrioventricular junctional tachycardia during heart block

The response of the atrioventricular (AV) junction to brief intense adrenergic stimulation applied during episodes of second degree heart block achieved by acetylcholinesterase paralysis in the AV junction was examined in six dogs. Despite profound depression of AV conduction due to enhanced cholinergic activity, strong local adrenergic stimulation still readily elicited AV junctional tachycardia. Increase in cholinomimetic influences in the AV junction did not prolong transatrial or His bundle-ventricular conduction times. During AV junctional rhythm and retrograde atrial capture (n = 4), neither the sequence of retrograde atrial activation nor the atrial electrogram configurations were altered. In the two remaining dogs the AV junctional tachycardia was associated with AV dissociation. These findings suggest that the acetylcholine-induced depression of AV conduction is located in the AV node region exclusively. More important, however, is the demonstration that retrograde atrial activation originating from a pacemaker located in the AV node or immediate vicinity could actually precede the inscription of the H spike by a considerable amount of time, further suggesting that anterograde conduction from the pacemaker site to the bundle of His is far more depressed by acetylcholine than is the concomitant retrograde conduction from the pacemaker site to the atrium. Thus, inference of the origin of a subsidiary pacemaker from the P wave configuration or the relation of the A wave to the His bundle electrogram, or both, may lead to erroneous conclusions.

The effects of negative chronotropic interventions on sinus node recovery time

SummaryThe effects of multiple increases in sinus cycle length on sinus node recovery time (SNRT) were examined in 5 dogs. Pacing was performed from the left atrial appendage for 30 and 60 seconds using at least 4 different pacing cycle lengths selected between 230 and 620 msec. Each dog received propranolol (1 mg/kg, IV) prior to any measurements. The effects of increases in sinus cycle length on SNRT were first assessed during 2 levels (4 and 8 Hz) of continuous vagal stimulation. From a control cycle length of 439±28 msec (mean±SE), the vagal stimulations lengthened the sinus cycle lengths to 604±10 msec and 758±16 msec respectively. Sinus cycle length was then prolonged by combined muscarinic and beta-receptor blockade resulting in a sinus cycle length of 549±9 msec. Autonomic blockade plus verapamil (3–10 mg IV) resulted in sinus cycle lengths of 612±14 and 721±18 msec respectively, which were not significantly different from those obtained with vagal stimulation. Data relating SNRT to the sinus cycle length, pacing cycle length, duration of pacing and the negative chronotropic interventions used to achieve the changes in the sinus cycle length were analyzed via covariance analysis. The results demonstrate that the single most important determinant of SNRT is the sinus cycle length. Furthermore, equivalent increases in sinus cycle length whether obtained by vagal stimulation, autonomic blockade or intravenous verapamil results in SNRTs that are not significantly different. Therefore, in the sinus node, changes in the rate of pacemaker activity, regardless of how they are achieved, will largely determine the changes in SNRT.

Differential effects of sympathetic activity on AV junctional automaticity and AV conduction

SummaryRapid ventricular response during episodes of supraventricular tachycardia are often followed, on abrupt cessation of the tachycardia, by prolonged pauses terminated by a sluggish and sometimes erratic escape of a supraventricular pacemaker. Such chronotropic-dromotropic paradoxes are readily reproduced in the animal laboratory following elimination of the sinus node and bilateral decentralization of the stellate ganglia and vagi. This study examined whether left stellate stimulation (0.5, 1, 2, 4, 8 and 16 Hz) or lack thereof differentially affected AV junctional automaticity and AV conduction. In the absence of any sympathetic neural activity (maximal sympathetic deficit), the AV junctional rate averaged a mere 22±2 percent of its peak performance, whereas under the same conditions, anterograde AV conduction averaged 73±5 percent and retrograde VA conduction 56 ±13 percent of their respective peak performances. On comparing the response curve (normalized responses) for AV junctional automaticity with that obtained for anterograde AV conduction the differences were significant at all frequencies between 0 and 4 Hz. Retrograde VA conduction (as assessed by the fastest ventricular pacing rate still conducted 1∶1 to the atria) was always significantly less than anterograde AV conduction (as assessed by the fastest atrial pacing still conducted 1∶1 to the ventricles). These results indicate that AV junctional automaticity is considerably more affected by sympathetic deficit than are either anterograde or retrograde AV conduction. In other words, AV junctional automaticity is far more dependent upon sympathetic input than AV conduction. While sympathetic influence is critical to the escape and maintenance of AV junctional automaticity both anterograde and retrograde AV conduction are remarkably resilient even under conditions of severe sympathetic deficit.

Influence of atrial mechanoreceptors upon the sympathetic efferent activity elicited during a cardiogenic chemoreflex in the dog

Two different cardiogenic reflexes were studied for their effects upon the activity recorded from the thoracic cardiac nerves of 7 chloralose-anesthetized dogs. Sympathetic efferent activity in 5 right and 7 left anterior ansa multifiber preparations was quantitatively analyzed. A cardiogenic hypertensive chemoreflex was induced by administration of serotonin (100 micrograms/ml, 2 ml) into the left atrium before, during and after inflation of balloons in the right and/or left atrial appendages. Balloon inflations alone resulted in heart rate increases of 5-20 bpm but arterial blood pressure, pulse pressure and end diastolic pressure were not significantly affected. Control serotonin-induced efferent discharges were 174 +/- 10% (mean +/- S.E.M.) of resting activity with a duration of 5.2 +/- 0.4 s. During inflation of both atrial balloons, the serotonin-induced efferent discharges were 165 +/- 14% (N.S.) of resting activity with a duration of 7.8 +/- 0.7 s (P less than 0.01). Following release of the balloons, the serotonin-induced discharges were 152 +/- 17% (N.S.) of resting activity with a duration of 4.9 +/- 0.4 s (N.S.). These results suggest that afferent signals from atrial mechanoreceptors can act to increase the duration but not the total intensity of the efferent sympathetic discharges elicited during a cardiogenic chemoreflex.