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Effects of Cardiac Denervation on Atrioventricular Nodal Accommodation and Hysteresis Bryan E. Fuhs, MD, and Kenneth A. Ellenbogen, MD

Conduction through the atrioventricular (AV) node is significantly altered by changes in autonomic tone. AV nodal accommodation (time-dependent changes in AV nodal conduction after a sudden change in atrial cycle length) and AV nodal hysteresis (asymmetry of AV nodal accommodation after directionally opposite atrial pacing cycle length changes) have been characterized in humans. Studies in dogs after cardiac transplantation suggest that the rapid phase of AV nodal accommodation is altered following ablation of neural input to the AV node. To determine if cardiac denervation alters AV nodal accommodation and hysteresis in humans, 13 patients after orthotopic cardiac transplantation and 12 control patients with normal AV nodal function were studied. Atrial pacing was performed for 1 minute at different pacing cycle lengths and AH or AV intervals were measured after cycle length changes. The rapid phase of accommodation is defined as the time required for the AV interval to reach 75% of the final AV interval. During abrupt changes from long to short pacing cycle lengths, the rapid phase of accommodation took 3.2 f 1.0 and 4.3 f 1.0 beats in control subjects and transplant patients, respectively (p = not significant [NS]). When going from short to long pacing cycle lengths, the rapid phase of accommodation took 1.7 f 1.2 and 2.1 f 1.8 beats in control subjects and transplant patients, respectively (p = NS). Hysteresis of 1.5 f 1.3 and 2.1 f 1.4 beats was noted in the control and transplant groups, respectively (p = NS). Transplant patients and control subjects behaved in a similar fashion during changes in atri-

From the Division of Cardiology, Department of Medicine, McGuire Veterans Administration Medical Center, and the Medical College of Virginia, Richmond, Virginia. This study was supported by funds from the Veterans Administration, Richmond, Virginia. Manuscript received March 21, 1991; revised manuscript received and accepted July 3 1, 1991. Address for reprints: Kenneth A. Ellenbogen, MD, Box 53, MCV Station, Medical College of Virginia, Richmond, Virginia 23298. 1458

THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 68

al pacing cycle length, suggesting that neural influences at rest do not play a major role in determining AV nodal accommodation and hysteresis. (Am J Cardiol 1991;6&1458-1464)

trioventricular (AV) nodal accommodation is the adaptation of AV nodal conduction after an abrupt change in atria1 pacing cycle length. The AV nodal responseto alterations in pacing cycle length is biphasic with most of the final AV interval change occurring within the first several beats.im5This early responseis termed the rapid phase of accommodation and may be defined as the time required to achieve75% of the final AV interval. The slow phaseof accommodation follows and is responsiblefor the last 25% of the final AV interval change. The rapid phase of AV nodal accommodation responds differently to asymmetric changesin pacing cycle length.6s7This differencein responseis termed hysteresisand is presentin both animals and humans. Several investigators have demonstratedthat AV nodal conduction is mediated by sympathetic and parasympathetic input, but the effect of autonomic input on AV node accommodation has not been well characterized in humans. Tuna et al8 studied AV nodal accommodation and hysteresis in dogs after cardiac transplantation. After cardiac denervation, the rapid phase of AV nodal accommodation is altered and no hysteresiswas observed. Basedon thesefindings, the investigatorssuggestedthat hysteresis(and the rapid phaseof AV nodal accommodation) results primarily from extrinsic (neural) modification of AV nodal conduction.8 In humans, initial observationsof AV nodal accommodation have been made after suddenchangesin atrial rate, but did not include systematicevaluation of accommodation using identical protocols to those used in animal studies.g-l1 We prospectively studied human AV nodal accommodation during symmetric (and opposite) atria1 pacing cycle length changes in a control group of subjects referred for electrophysiology study and a group of patients after orthotopic cardiac transplantation. We sought to describe accommodation and hysteresis following orthotopic cardiac transplantation

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and compare that with control subjectsundergoing the same pacing protocol. METHODS Two groups of male patients were prospectively studied after informed written consent was obtained. The protocol was approved by the institutional review boards of the McGuire Veterans Administration Medical Center and the Medical College of Virginia. All cardiac medications that affect sinus node or AV nodal conduction (e.g., digoxin, p blockers, calcium antagonists, and type la antiarrhythmic drugs) were discontinued for at least 4 to 5 half-lives before the study. The control group consisted of 12 men (mean age 54 f 9 years [range 36 to 691)referred for electrophysiologic study to evaluate documentedor suspectedcardiac arrhythmias. All patients were in normal sinus rhythm and had no evidenceof sinus or AV nodal disease during electrophysiologic testing. Three patients had no structural heart disease,and 7 patients had angiographically documented coronary artery disease. The second group consisted of 13 patients (mean age 50 f 8 years [range 34 to 613) who were studied 1 to 84 months (mean 33 f 10) after orthotopic cardiac transplantation. Thirteen patients were taking cyclosporin A, 11 patients were taking azathioprine and 4 patients were taking prednisone. Seven patients were taking furosemide and most were treated with angiotensin-converting enzyme inhibitors for hypertension. Ten patients had a normal 1Zlead electrocardiogram with normal PR, QRS and QT intervals, and 3 patients had a QRS interval of 120 ms. Cardiac transplant patients were studied in the resting supine state 15 minutes after endomyocardial biopsy. Electrophysidogic study: Studies were performed in the fasting, nonsedatedstate in all patients. In the control patients, 2 or 3 quadripolar catheters were introduced through the right femoral vein and positioned in the right atria1 appendage,acrossthe tricuspid valve to record a His bundle, and in the right ventricular apex. In the cardiac transplant patients, a hexapolar catheter was advancedfrom the right internal jugular vein to the right atrium where a donor atria1 electrogram and farfield ventricular electrogram were recorded. Intracardiac electrograms were filtered at 30 to 500 Hz and simultaneously displayed with 3 surface electrocardiographic leads on a multichannel recorder (Electronics for Medicine, VR-16, Pleasantville, New York). Pacing was performed at twice diastolic threshold (40 ms longer than the Wenckebach cycle length. After 1 minute of atria1 pacing at the shorter cycle length, the atria1 pacing cycle length was then rapidly switched to the original (longer) atria1 pacing cycle length. The total change in AV interval was measured and the time interval (and number of beats) required to achieve75% of the final AV interval was measured,and designated the rapid phase of accommodation. Hysteresis was measuredas the difference in the number of beats (and time) between accommodation in 1 direction and accommodation in the opposite direction. AV nodal conduction was measured continuously by recording the AH or AV interval, or both, in control patients and the AV interval in transplant patients. In control (n = 12) and transplant (n = 2) patients where AH and AV intervals were simultaneously measured, AH intervals paralleled AV intervals. AH and AV intervals were recorded at a paper speedof 100 mm/s and measurable to f 5 ms. AH or AV intervals, or both, were measured during the 10 secondsbefore rapid change.To be considered stable the measured intervals did not vary by >5 ms. hdidtiOllS:

ATRIOVENTRICULAR

NODAL ACCOMMODA-

The time-dependentchange in AV nodal conduction after a sudden change in atria1 cycle length. RAPIDPHASEOFACCOMMODATION: Thetimeperiodrequired for 75% of the final AV interval to be obtained. HYSTERESIS: Asymmetry of AV nodal accommodation to rapid changes (in opposite directions) in atria1 pacing cycle length. SHORT PACING CYCLE LENGTH: The shortest cycle length that consistent 1:1 AV conduction could be verified in a l-step protocol (generally 140 ms above Wenckebach cycle length).

TION:

NODAL ACCOMMODATION AFTER CARDIAC TRANSPLANTATION

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CYCLE LENGTH: A PaCiIlg CyCk 20 t0 50 faster than the patient’s sinus cycle length at rest. Statistics: Both intragroup and intergroup statistical comparisonswere performed. Statistical comparison of the AV nodal responsein each group to symmetric pacing cycle length changes(short versuslong pacing cycle length) was performed with paired t testing using the Bonferonni correction for multiple comparisons.A corrected p value

Effects of cardiac denervation on atrioventricular nodal accommodation and hysteresis.

Conduction through the atrioventricular (AV) node is significantly altered by changes in autonomic tone. AV nodal accommodation (time-dependent change...
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