Sinus Node Recovery Time Research Articles

A gastroesophageal electrode for electrophysiological studies.

A novel gastroesophageal electrode has been developed capable of atrial and ventricular pacing. We performed electrophysiological studies using the gastroesophageal electrode (Esothoracic) and compared the results with the standard endocardial approach. The flexible polythene gastroesophageal electrode was passed into the stomach under light sedation. Five ring electrodes, now positioned in the lower esophagus were used for bipolar atrial pacing and recording. Ventricular pacing was performed using a cathodic point source on the gastroesophageal electrode tip; the indifferent electrode (anode) was a high impedance chest pad. Parameters of sinus and AV nodal function were obtained by atrial pacing. Programmed ventricular stimulation was performed using a standard protocol. These electrophysiological parameters were subsequently determined using the endocardial approach. There was close correlation between measurements of sinus and AV node function using the two approaches in 48 subjects: sinus node recovery time (SNRT) r2 = 0.70, corrected sinus node recovery time (CSNRT) r2 = 0.87, AV Wenckebach cycle length (AVWCL) r2 = 0.97. The degree of agreement between the two approaches was estimated by the mean difference delta and standard deviation of the difference sigma (SNRT delta = 40 ms, sigma = 257 ms; CSNRT sigma = 14 ms, delta = 164 ms; AVWCL sigma = 7 ms, delta = 16 ms). Programmed ventricular stimulation was performed in 15 of 48 subjects with known or suspected ventricular tachyarrhythmias. Seven had ventricular tachycardia induced using both esothoracic and endocardial programmed ventricular stimulation. One subject was noninducible using esothoracic programmed ventricular stimulation, but inducible at endocardial electrophysiological studies. Another subject was inducible at esothoracic electrophysiological studies, but noninducible using endocardial programmed ventricular stimulation. Six subjects were noninducible using both endocardial and esothoracic programmed ventricular stimulation. The gastroesophageal electrode permits reliable atrial and ventricular pacing without transvenous catheterization or fluoroscopy. Electrophysiological parameters determined using this electrode are similar to those obtained using endocardial stimulation.

Propofol does not affect the canine cardiac conduction system under autonomic blockade.

To determine the effects of propofol on the cardiac conduction system in dogs with pharmacological autonomic blockade. In eight mongrel dogs receiving 6 mg.kg-1.hr-1 propofol and vecuronium under pharmacological autonomic blockade with atropine and propranolol the infusion rates of propofol were increased from 6, (baseline), to 12, 18 and 24 mg.kg-1.hr-1 at 60-min intervals. An electrophysiological study assessed sinus rate, sinus node recovery time, corrected sinus node recovery time, intraatrial conduction time, AV nodal effective refractory period, Wenckebach cycle length and AV conduction times. Electrocardiographical variables and arterial pressures were also measured. All measurements were repeated at 30 min after the beginning of each infusion of propofol. Propofol did not produce direct effects on the electrophysiological or electrocardiographical variables at any infusion rates. Heart rates did not change at higher infusion rates in the presence of decreases in arterial pressures. Propofol did not affect the cardiac conduction system in the presence of autonomic blockade. Thus, the direct cardiac effects of propofol do not play a causative role in the genesis of propofol-associated bradyarrhythmias.

Heterogeneous Changes in Electrophysiologic Properties in the Paroxysmal and Chronically Fibrillating Human Atrium

The regional changes in atrial electrophysiologic properties related to atrial fibrillation (AF) in patients with paroxysmal AF (PAF) and chronic AF (CAF) remain unclear. The purpose of this study was to investigate the regional changes in atrial electrophysiology in patients with AF. We evaluated the atrial electrophysiology at different sites (high right atrium, low right atrium [LRA], and distal coronary sinus [DCS]) in 11 patients with CAF, 8 patients with PAF, and 10 controls. Patients with CAF had significantly prolonged interatrial conduction and corrected sinus node recovery time, and shortened atrial effective refractory period (ERP) with loss of rate-related adaptation in the DCS, but had paradoxic prolongation of atrial ERP in the LRA, as compared with patients with PAF and the controls. As a result, the spatial distribution of atrial ERP that was observed in the controls and in patients with PAF was reversed in patients with CAF, without an increase in the dispersion of atrial refractoriness. Patients with PAF showed intermediate changes in atrial conduction times and atrial refractoriness as compared with patients with CAF and controls. There was a regional heterogeneity on the changes of atrial electrophysiology in different parts of the atrium, and the "normal" spatial distribution of atrial refractoriness was reversed in patients with CAF. The electrophysiologic changes observed in patients with PAF appear to behave as if in transition from the control state to CAF, suggesting progressive changes in atrial electrophysiologic properties.

Possible contribution of alpha-adrenergic abnormalities to cerebral ischemia in the patients with sinus bradycardia. Analysis by pharmacologic autonomic nervous test

Syncope of patients with bradyarrhythmia is perceived as severe sign of low cardiac output caused by bradycardia and as a major criteria for pacemaker implantation (PMI). However, it has been reported that PMI can not always prevent syncope; it has been suggested that not bradycardia but an abnormality of the autonomic nervous system plays a part in syncope. To investigate the relation between autonomic nervous dysfunction and syncope in cases of sinus bradycardia (SB). Thirty-nine patients with SB were divided into two groups according to the presence (group S, n = 16, 46.9 +/- 20.0 years) or absence (group N, n = 23, 40.4 +/- 17.6 years) of syncope or presyncope. Corrected sinus node recovery time (CSNRT) was measured by electrophysiologic study. Pharmacologic autonomic nervous tests were performed as follows in a quiet room. Increased HR by application of 0.04 mg/kg atropine (para-tone), and by 0.004 microgram/kg/min isoproterenol divided by 0.004 (beta-sens) were evaluated, beta-tone was obtained by subtracting HR after application of propranolol (0.2 mg/kg) from that of atropine. Basal beta-sympathetic activity was evaluated by beta-sec that was obtained by beta-tone/beta-sens. Increased SBP by application of 0.4 microgram/kg/min phenylephrine divided by 0.4 (alpha-sens) was evaluated. alpha-tone was obtained by subtracting minimum SBP after 0.2 mg/kg phentolamine from SBP after application of propranolol. Basal alpha-sympathetic activity was evaluated by alpha-sec, that was obtained by alpha-tone/alpha-sens. There were no significant differences in basal clinical characteristics (age, sex, cardiac function) between the groups. The parameters of the functions of parasympathetic and beta-sympathetic receptors (para-tone, beta-sens, beta-tone, beta-sec) showed no significant differences between the groups, alpha-sens was attenuated (P < 0.01) and alpha-sec was augmented (P < 0.0001) significantly in group S. It was suggested that syncope or presyncope in SB patients could be attributed to failure of vasoconstriction mediated by alpha-sympathetic receptor but to severity of sinus node dysfunction.

Alterations of sinus node recovery time after radiofrequency catheter ablation of the incessant atrioventricular nodal reentrant tachycardia

Alterations of sinus node recovery time after radiofrequency catheter ablation of the incessant atrioventricular nodal reentrant tachycardia

Cardiac electrophysiologic effects of norepinephrine in human beings

Background: The electrophysiologic effects of norepinephrine (NE) in human beings have not been previously described. Methods: The electrophysiologic effects of NE infused at a rate of 25 ng/kg/min were determined in 21 patients with a mean age of 41 ± 11 years and without structural heart disease who underwent an electrophysiology procedure. In a subgroup of 10 patients electrophysiologic parameters were measured at baseline, after the infusion of NE, and after administration of β-blockade while in continuous NE infusion. Results: The baseline NE plasma concentration of 298 ± 153 pg/ml increased to 708 ± 419 pg/ml after the infusion of NE. NE significantly increased the mean blood pressure, sinus cycle length, corrected sinus node recovery time, ventriculoatrial block cycle length, and the atrial and ventricular effective refractory periods. In a subset of 10 patients 0.2 mg/kg propranolol administered during continued infusion of NE resulted in a further increase in sinus cycle length, atrial-His interval, and ventricular refractoriness. Conclusion: A physiologic elevation in the plasma NE concentration results in a depression of sinus node function and atrioventricular conduction and in prolongation of atrial and ventricular refractoriness. Some of NE's effects are partially offset by β-adrenergic stimulation. (Am Heart J 1998;135:945-51.)

Benign prognosis of early sinus node dysfunction after orthotopic cardiac transplantation.

Previous reports raised concern about the prognosis of patients with sinus node (SN) dysfunction after cardiac transplantation and led to a low threshold for permanent pacemaker (PM) placement at most institutions. The present study addresses the survival in patients with normal and impaired post operative SN function and the effect of permanent pacing with respect to overall and cardiac mortality. There were 120 patients with normal (corrected SN recovery time < 520 ms, group I) and 47 patients with imparied SN function (corrected SN recovery time > 520 ms and/or sinus arrest +/- escape rhythms). Pacing support was deemed unnecessary in 23 of 47 patients with SN dysfunction (group II; asymptomatic SN bradycardia and corrected SN recovery time 3,812 +/- 5,800 ms) while a total of 24 patients had PM placement a mean of 29 +/- 44 days after transplantation (symptomatic bradycardia or absence of sinus rhythm at discharge, group III). Patients were followed for a mean of 46.7 months. Thirty-five deaths occurred during the study period. Sixteen deaths were cardiac but none were causally related to the SN dysfunction (graft failure due to rejection or atheropathy n = 14; myocardial infarction n = 2). Four of these cardiac deaths were sudden and all occurred in the presence of widespread structural abnormalities (rejection/vasculopathy/myocardial infarction). SN dysfunction was not related to overall (P = 0.25) or cardiac mortality (P = 0.33). Regarding either endpoint, patients who had permanent PM placement did no better than their unpaced counterparts in group II (P = 0.53 and P = 0.33, overall and cardiac mortality, respectively). Likewise, survival did not differ between groups I and III for either endpoint (P = 0.77, P = 0.65, respectively). These data suggest that patients with mild SN abnormality, who are in sinus rhythm at the time of discharge, can be followed by observation without specific therapy.

Correlation between initial potentials on a signal-averaged P-wave and indice of electrophysiologic measurements in the right atrium.

The aim of this study was to determine whether initial potentials of the P-wave on a signal-averaged electrocardiogram (SAE) during sinus rhythm reflect indices of electrophysiologic measurements in the high lateral right atrium. A total of 67 patients underwent P-wave signal averaging during electrophysiologic testing. The correlation between root mean square voltages for the initial 10 and 20 msec of the P-wave on the SAE and indices of electrophysiologic measurements, sinus node recovery time (SRT) and sinoatrial conduction time (SACT), obtained from programmed stimuli, was evaluated. It was found that the initial potentials of the P-wave on the SAE correlated negatively with SRT and SACT (-0.37 < or = r < or = -0.30). It was concluded that the initial potentials correlated with indices of electrophysiologic measurements, although the statistical significance was weak.

Radiofrequency catheter ablation of the atria eliminates pacing-induced sustained atrial fibrillation and reduces connexin 43 in dogs.

We assessed the effects of radiofrequency catheter ablation (RFCA) of the atrial epicardium on pacing-induced sustained atrial fibrillation (AF) and the expression and distribution of the intercellular gap junction protein connexin 43 (Cx43) in dogs. In 12 mongrel dogs, after creation of complete AV block and implantation of a ventricular inhibited pacemaker, a high-rate pulse generator (20 to 30 Hz to induce AF) was implanted in the neck, connected to a right atrial endocardial pacing lead, and used to pace the atrium for 10 to 14 weeks. In group 1 (n=9 dogs), corrected sinus node recovery time (CSNRT), P-wave duration, 24-hour Holter ECG, maximal heart rate (MHR) in response to isoproterenol, and intrinsic heart rate (IHR) after atropine (0.04 mg/kg) and propranolol were measured before and after atrial pacing and RFCA. Group 2 dogs were used to assess the effect of chronic AF alone on Cx43 expression and distribution. All group 1 dogs developed sustained (>24 hours) AF. Right-sided RFCA of the atria eliminated the sustained AF in 5 dogs, but both right and left atrial RFCA was required to abolish sustained AF in the other 4 dogs. After RFCA restored sinus rhythm, CSNRT and P-wave duration were prolonged and MHR and IHR were decreased. Chronic rapid atrial pacing (group 2) increased the expression of Cx43, which was absent in ablated areas and markedly depressed in viable atrial myocytes near the ablation zones (group 1). Rapid atrial pacing for long time periods induced sustained AF that can be eliminated by linear right and left atrial lesions created with RFCA, with preservation of sinus rhythm and atrial contractile function. Chronic AF increased the expression and distribution of gap junction protein Cx43, which became reduced in ablated and nearby nonablated areas.

Serial Measures of Sinoatrial and Atrioventricular Nodal Function in Ambulatory Patients

We hypothesized that the outpatient assessment of SA and AV nodal (SAN, AVN) function could be a useful tool to determine the effectiveness of drugs and other treatments. We sought to examine the reproducibility, safety and ease of acquiring serial measurements of these parameters. Ten patients with permanent pacemakers underwent low current chest wall stimulation while their device was programmed to unipolar atrial triggered mode. Measurements at multiple conditioning drive train frequencies were obtained for: sinus nodal recovery time (SNRT); corrected sinus nodal recovery time (CSNRT); SA conduction time (SACT); AVN block cycle length (AVNBCL); and AVN effective refractory period (AVNERP). AVN function curves were also constructed. All studies were repeated after 2 weeks. Measures of sinus nodal and AVN function did not show significant differences between the two studies. The following co-efficients of correlation were obtained: SNRT800, r = 0.79; CSNRT800, r = 0.71; SNRT600, r = 0.71; CSNRT600, r = 0.44; SACT, r = 0.75; AVNBCL, r = 0.98; AVNERP800, r = 0.55; and AVNERP600, r = 0.99. AVN function curves did not significantly differ between week 1 versus week 2 at conditioning drive trains of either 800 ms or 600 ms. These data suggest that serial noninvasive electrophysiological measures of AVN and SAN function are reproducible over 2 weeks. Using data in this study, estimates of the sample size necessary for the evaluation of the effects of investigational drugs on the SAN and AVN in future studies are possible.

Investigations to characterize the antiarrhythmic action of bergamottine, a furocoumarin isolated from bergamot oil

Bergamottine is a furocoumarin isolated from the non-volatile essential oil of Citrus bergamia Risso (Bergamot, Rutaceae) with antiarrhythmic properties. We investigated and classified its mechanism of action according to Vaughan Williams. We have found that bergamottine at a concentration range of 5-20 μg/mL (14.7-59 μM) decreased the frequency and the force of the contraction in spontaneously beating guinea-pig right atria and electrically paced left atria in a concentration-dependent manner. Furthermore this furocoumarin caused a parallel shift of the dose-response curve to CaCl 2 similar to that of verapamil in the electrically driven left atrium, indicating a possible Ca-antagonistic property. Bergamottine (1 mg/kg i.v.) significantly prolonged the atrioventricular conduction time, the corrected sinus-node recovery time and the corrected sinus-atrial conduction time in anaesthetized rabbits. Bergamottine did not inhibit isoprenaline-induced positive chronotropic responses in atrial muscle, indicating that it has no β-blocking activity, and did not show significant local-anaesthetic property in the guinea-pig intradermal wheal test. These results demonstrate that bergamottine seems to be an antiarrhythmic drug having class IV (inhibitor of calcium transport) type activity.

The acute effects of intravenously administered mibefradil, a new calcium antagonist, on the electrophysiologic characteristics of the human heart

This multicenter, double-blind, placebo-controlled, parallel-group study was designed to assess the acute effects of intravenous mibefradil on the electrophysiologic characteristics of the human heart. Seventy-one patients referred for routine electrophysiologic testing were randomized to receive one of three intravenous treatments: placebo n = 23, 15 mg mibefradil in 15 min followed by 25 mg in 60 min (group 1, n = 24), or 35 mg mibefradil in 15 min followed by 45 mg in 60 min (group 2, n = 24). Electrophysiologic evaluations were performed prior to study drug administration and 30 min after the start of the infusion. Plasma samples were obtained at the start of the infusion and after 15, 75, and 105 min. Sinus node recovery time decreased significantly in Group 1 patients (-103 ms). Corrected sinus node recovery time in group 2 patients was 68.7 ms (P = 0.053). Compared to placebo, mibefradil produced mild but significant slowing of conduction in group 2 patients as manifested by an increase in the AH interval of 6.7 ms. Atrioventricular (AV) nodal refractoriness was increased, as indicated by a prolongation of the Wenckebach point in patients in both group 1 (32.1 ms) and group 2 (32.5 ms), compared to placebo. All adverse events were classified as mild to moderate and only one event (vasovagal attack) was considered to be treatment related. At plasma levels close to those found after chronic oral administration of 50 and 100 mg mibefradil, the higher dose produced an increase in corrected sinus node recovery time. Mibefradil also produced small but significant effects on AV nodal conduction and increased AV nodal refractoriness. Mibefradil had no effect on any other electrophysiologic parameter and was well tolerated.

Electrophysiological Remodeling of the Heart Owing to Rate

Although damage to the heart from inflammation and infarction are well-established stimuli that trigger major cardiac remodeling, it has been known since 1954 that a persistent supraventricular tachycardia also can alter cardiac structure and function.1 This clinical observation was exploited 8 years later when it was demonstrated that rapid stimulation of the normal heart could produce reversible congestive heart failure.2 Since then, rapid pacing has been used frequently to create an investigational animal model of heart failure. The effects of prolonged pacing-induced tachycardia, in the range of 250 bpm for 3 or 4 weeks, has been studied in depth in several animal species and has been shown to cause extensive myocardial remodeling. Biventricular enlargement with reduced wall thickness and no increase in muscle mass, reduced cross-sectional myocyte area and increased length, disarray of myofibril alignment and cytoarchitecture, increases in contractile protein degradation, and destruction of the supporting myocardial collagen matrix represent some of the structural changes contributing to reduced ventricular function.3 Diminished responsiveness to β-adrenoceptor stimulation caused by a reduction in β-receptor density and a variety of alterations in the adrenergic signaling processes also occur.4 Replacement fibrosis, loss of cells, and reactive hypertrophy of the remaining cells have been noted recently.5 mRNA levels for specific cytoskeletal proteins increase, along with alterations in cytoskeletal architecture6 and abnormalities in phospholamban.7 In pigs subjected to 3 weeks of a tachycardia-induced cardiomyopathy, myocyte action potential showed reduced membrane resting potential, reduced amplitude and upstroke velocity, and prolonged duration at 90% repolarization. Peak L-type Ca2+ current density was reduced because of an absolute reduction in L-type Ca2+ current flow into the myocyte possibly caused by reduced open probability of the channel.8 However, in dogs that had rapid ventricular pacing for 3 to 4 weeks, action …

Electrophysiological abnormalities and arrhythmias in alpha MHC mutant familial hypertrophic cardiomyopathy mice.

A new mouse cardiac electrophysiology method was used to study mice harboring an alpha-myosin heavy chain Arg403Gln missense mutation (alpha-MHC403/+), which results in histological and hemodynamic abnormalities characteristic of familial hypertrophic cardiomyopathy (FHC) and sudden death of uncertain etiology during exercise. Wild-type animals had completely normal cardiac electrophysiology. In contrast, FHC mice demonstrated (a) electrocardiographic abnormalities including prolonged repolarization intervals and rightward axis; (b) electrophysiological abnormalities including heterogeneous ventricular conduction properties and prolonged sinus node recovery time; and (c) inducible ventricular ectopy. These data identify distinct electrophysiologic abnormalities in FHC mice with a specific alpha-myosin mutation, and also validate a novel method to explore in vivo the relationship between specific genotypes and their electrophysiologic phenotypes.

Sinus node dysfunction in acute inferior myocardial infarction. Role of sinus node artery and clinical course in patients with one-vessel coronary artery disease.

To determine the role of the sinus node artery and the clinical course in postmyocardial infarction sinus node dysfunction, 27 patients with acute inferior myocardial infarction and single-vessel coronary artery disease were studied. In 13 patients (group 1) the infarct-related coronary artery was occluded proximally and in 14 (group 2) distally to the site of origin of the sinus node artery. At electrophysiology, performed 10 +/- 3 days from the acute event, basal and intrinsic heart rate were lower in group 1 compared to group 2 patients (54 +/- 4.8 vs. 69 +/- 7 beats/min, p = 0.001, and 66 +/- 7 vs. 76 +/- 8 beats/min, p = 0.006, respectively) while basal and intrinsic corrected sinus node recovery times were prolonged in group 1 compared to group 2 patients (585 +/- 49.3 vs. 324 +/- 61.3 ms, p = 0.0001, and 601 +/- 39.1 vs. 335 +/- 73 ms, p = 0.0001). During a 6-month follow-up no episodes of dizziness, syncope or angina were reported. Moreover, at the end of follow-up resting heart rate (70 +/- 11 vs. 73 +/- 7 beats/min, nonsignificant), maximal exercise heart rate (166 +/- 19 vs. 170 +/- 23 beats/min, nonsignificant), and exercise time (491 +/- 120 vs. 480 +/- 155 s, nonsignificant) were similar between the two groups and no exercise-induced ischemic ST segment depression was observed. Sinus node dysfunction in patients with inferior myocardial infarction and one-vessel disease is related to the occlusion of the infarct-related coronary artery proximal to the site of origin of the sinus node artery and is not associated with increased cardiovascular morbidity in the first 6 months from the acute event.

Pacing-Induced Chronic Atrial Fibrillation Impairs Sinus Node Function in Dogs

We assessed the effects of pacing-induced chronic atrial fibrillation (AF) on sinus node function, intra-atrial conduction, and atrial refractoriness. In 15 mongrel dogs (20 to 30 kg), AV nodal block was produced by radiofrequency catheter ablation, and a ventricular-inhibited (VVI) pacemaker (Minix 8330, Medtronic) was implanted and programmed to pace at 80 pulses per minute. In 11 of these dogs, right atrial endocardial pacing leads were connected to a pulse generator (Itrel 7432, Medtronic) and set at a rate of 20 Hz to induce AF. Corrected sinus node recovery time, P-wave duration, 24-hour Holter ECG to assess AF duration, maximal heart rate in response to isoproterenol (10 micrograms/min), intrinsic heart rate after administration of atropine (0.04 mg/kg) and propranolol (0.1 mg/kg), and atrial effective refractory periods (ERPs) were obtained at baseline (EPS-1) and after 2 to 6 weeks (EPS-2) of VVI pacing alone (n = 4) or VVI pacing and rapid atrial pacing (n = 11). At EPS-2, corrected sinus node recovery time and P-wave duration were prolonged, maximal heart rate and intrinsic heart rate were decreased, atrial ERPs were shortened, and the duration of AF was increased significantly compared with EPS-1. These changes partially reversed toward baseline 1 week after conversion to sinus rhythm. Sinus node function and AF inducibility observed in the control dogs that underwent ventricular pacing alone (n = 4) did not change. Pacing-induced chronic AF induces sinus node dysfunction, prolongs intra-atrial conduction time, shortens atrial refractoriness, and perpetuates AF, changes that reverse gradually after termination of AF.

In vivo cardiac electrophysiology studies in the mouse.

This report describes a novel in vivo mouse epicardial cardiac electrophysiology study based on clinical protocols used to evaluate cardiac conduction in human patients. The technique allows extensive electrophysiological evaluation, including the response to pacing, programmed stimulation, and pharmacological agents. Surface six-lead ECG data from 18 C57BL/6J mice are presented. Normal cardiac conduction properties for 14 of 18 mice that underwent the procedure are summarized, including determination of sinus node recovery times, AV conduction properties, and atrial, AV, and ventricular effective refractory periods. A subset of six mice was studied after the administration of either procainamide (n = 3) or quinidine (n = 3). All animals in the procainamide group developed either second-degree or complete AV block spontaneously. The sinus cycle length and refractory periods prolonged on procainamide or quinidine, but no tachyarrhythmias could be induced with atrial or ventricular programmed stimulation. This mouse electrophysiology method allows rapid assessment of the conduction properties of the murine heart. The ability to analyze cardiac conduction in normal and transgenic mice provides a powerful tool for examining molecular electrophysiological mechanisms in normal physiology and disease states.

Reproducibility of electrophysiological measurements in cardiac transplant recipients.

The clinical usefulness of certain electrophysiological measurements, particularly those of sinus node function, is limited by variation in autonomic tone resulting in poor reproducibility. The denervated transplanted heart is not susceptible to direct autonomic control and, therefore, electrophysiological measurements may be more reproducible in this group. To our knowledge, this hypothesis has not previously been systematically evaluated. Ten adult recipients underwent serial electrophysiological studies between 10-18 days after cardiac transplantation. Five studies were performed at 2-hour intervals during a single day, between 9:00 a.m. and 5:00 p.m. Spontaneous cycle length (SCL) was recorded. Sinus node recovery time (SNRT), sinoatrial conduction time (SACT), and atrioventricular (AV) Wenckebach cycle length were measured using standard techniques. The effective refractory periods of the complete AV conducting system (AVERP), atrium (AERP), and ventricle (VERP) were measured. Corrected maximal SNRT was normal in all subjects. Mean coefficients of variation (Cv) for SCL, corrected maximal SNRT, and SACT were 2.8%, 7.4%, and 3.5%, respectively. AVERP was less than AERP in seven subjects, limiting further analysis. The mean Cv for AV Wenckebach cycle length was 2.1%. The mean coefficients of variation for AERP were 3.6% and 3.7%, and for VERP 3% and 3.3%, at 600- and 400-ms drive cycle lengths, respectively. Previous studies report much greater variation in innervated subjects particularly of indices of sinus node function. Thus, the reproducibility of electrophysiological measurements of sinus and AV node function in the transplanted heart is better than in normal subjects. This may have important implications for the reliability of electrophysiological testing in transplant recipients.

Sinus node recovery time assessment revisited: role of pharmacologic blockade of the autonomic nervous system.

Sinus node recovery time assessment is used to diagnose clinically significant sinus node dysfunction (SND) when Holter has failed to prove a relationship between sinus bradyarrhythmias and symptoms, but consensus has not been reached as to the value of including assessment after pharmacologic blockade of the autonomic nervous system. This issue was addressed in the present study performed on 52 patients with syncope or presyncope/dizziness (n = 48), sinus bradyarrhythmias (n = 45), or both (n = 41). Group 1 consisted of 13 patients with a proven relationship between symptoms and sinus bradyarrhythmias. Group 2 consisted of 39 patients with suspected SND. The protocol included three pacing periods at two pacing rates and was performed at baseline (n = 52), after single doses of atropine and propranolol (0.02 mg/kg and 0.1 mg/kg, respectively) (n = 41), and again after a second dose (n = 29). The sensitivity of prolonged recovery times was 77% in group 1. Among group 2 patients, 56% had prolonged recovery times at baseline (79% when including the results after the first dose of drugs). The second dose did not contribute diagnostic information, but it caused significant adverse reactions in 7 of 29 patients (P < 0.001). These 7 patients were all older than 60 years. Assessment of sinus node recovery time after pharmacologic blockade of the autonomic nervous system thus increases the sensitivity of the method in patients with suspected SND and normal baseline results. However, only 50% of the initially suggested doses of atropine and propranolol is sufficient and eliminates the risk for significant adverse reactions.

Evidence for time-dependent autonomic cardiac reinnervation in children subsequent to transplantation of the heart

AbstractAutonomic denervation has been assumed to persist after orthotopic heart transplantation. Analyzing spontaneous and induced variations of heart rate, the status of autonomic cardiac innervation was investigated in six children 19–37 months after cardiac transplantation. The age at the time of transplantation varied from three weeks to 15.4 years. Heart rate variability was assessed on 24-hour Holter recordings by calculating time-domain indices (standard deviation of all RR intervals; standard deviation of the mean RR intervals from successive five-minute periods; mean of the standard deviations of RR intervals from successive five-minute periods; proportion of adjacent RR intervals &gt; 50 msec different; square root of mean square successive differences in RR intervals) and frequency-domain variables (low frequency power, high frequency power and total spectrum power). Sinus node recovery time, sinoatrial conduction time and post-pacing cycle lengths were examined at different rates of endocardial atrial pacing. After the first year subsequent to transplantation, standard deviation of the mean RR intervals reached the normal range in four patients, whereas the other time-domain variables became normal in two patients. Both patients displayed normal or near-normal power spectrums of heart rate with normal day-to-night variations. For the remaining patients, spectrums of heart rate failed to show the main frequency peaks. Only the patient with normal variability in heart rate exhibited a decrease in corrected sinus node recovery time at higher stimulation rates, shortening of the first recovery cycle below the pre-pacing level, and a rapid decline of the accelerated post-pacing heart rate as described in innervated hearts. These results suggest the evolution of time-dependent efferent autonomic reinnervation after cardiac transplantation in children.