Sinoatrial Conduction Time Research Articles

Inhibition by E-4031 of the prolongation of the first returning cycle length after overdrive in anesthetized dog hearts.

Prolongation of the functional recovery of the sinoatrial (SA) nodal pacemaker activity after overdrive, "overdrive suppression," is determined by intrinsic pacemaker activity, pacemaker site, and SA conduction. We investigated the effects of E-4031, a blocker of a rapid type of the delayed rectifier K+ current (Ikr) and stimulation of the intracardiac parasympathetic nerves to the SA nodal region (SAP) on the prolongation of the first returning cycle length (1st RCL) after overdrive in autonomically decentralized hearts of open-chest anesthetized dogs. Second and third RCLs also were measured. We determined SA node recovery time (SNRT) and corrected SNRT (CSNRT) after atrial pacing at rates of 120, 150, and 200% of the control rate for 1 min and also determined SA conduction time (SACT) by the constant-atrial-pacing method. E-4031 (0.1-3 micromol/kg i.v.) increased the sinus cycle length (SCL) and SNRT dose dependently. However, E-4031 decreased CSNRT when the pacing rate was low or the number of pacing stimuli was small, although the agent did not induce a significant change in CSNRT when sufficient pacing stimuli were applied. E-4031 decreased SACT dose dependently. After E-4031 treatment. we observed changes in atrial electrical configurations, suggesting the possibility of pacemaker shift. When SAP stimulation increased SCL, SNRT, CSNRT, and SACT, E-4031 selectively inhibited the prolongation of SCL by SAP stimulation but did not affect the prolongation of CSNRT or SACT. These results suggest that functional recovery of the SA nodal pacemaker activity after overdrive is regulated by Ikr at least in part and that Ikr inhibition attenuates prolongation of the SCL but not the 1st RCL induced by parasympathetic nerve activation in the heart in situ.

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.

Electrophysiologic assessment of calcium channel blockers in transplanted hearts: An experimental study

The effects of calcium channel blockers on automaticity, conduction, and refractoriness were studied in a model of heterotopic heart transplantation in dogs, which combined an innervated heart (recipient) and a denervated one (donor). Following the surgical procedure, 0.2 mg/kg verapamil (n = 10), 0.15 mg/kg diltiazem (n = 10), or 5 μg/kg + 30 μg/kg/h nifedipine (n = 10) was administered intravenously. In basal situation and after drug administration, each heart was assessed for AV interval, cycle length, sinoatrial conduction time, atrioventricular node antegrade block point, and atrioventricular node and ventricular refractory periods; electrocardiographic PR and QT intervals and QRS complexes; systemic arterial, pulmonary artery, central venous, and pulmonary capillary wedge pressures; and cardiac output. The depressor effects of these calcium channel blockers on automaticity, refractoriness, and conduction were more intense in the transplanted hearts, very possibly because of the absence of adrenergic reflexes mediated by the autonomic nervous system; in particular, verapamil produced a great depression of sinus automaticity in a large number of cases.

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.

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.

Invasive electrophysiological evaluation of patients with sleep apnoea-associated ventricular asystole-methods and preliminary results.

Twelve patients (aged 48 +/- 12 y) with ventricular asystole of >3 s due to complete atrioventricular (AV) block (n = 8), sinoatrial (SA) block or sinus node arrest (n = 3) or both (n = 1) associated with obstructive sleep apnoea underwent invasive electrophysiological evaluation of sinus node function and AV conduction properties before and after administration of atropine (0.02 mg kg-1). Ventricular asystole lasted for 5.9 +/- 2.8 s (range 3.1-13 s). Sinus node function was assessed by measurement of sinus node recovery time, sinoatrial conduction time, and the response of sinus rate to atropine. Parameters of AV-conduction assessment included AH- and HV-intervals, AV- and VA-Wenckebach periods, and effective refractory period of the AV node before and after atropine. Sinus node function was normal in 11 of the 12 study patients and moderately abnormal in 1 patient. AV-nodal function was normal in 8 patients and moderately abnormal in 4 patients. A slightly prolonged HV-interval (59-63 ms) was present in 6 patients. Intra- or infra His block was not observed in any patient. In conclusion, normal or only moderately abnormal electrophysiological findings in patients with sleep apnoea-associated ventricular asystole suggest that a neurally mediated cardioinhibitory reflex may cause ventricular asystole in these patients. This sleep apnoea-triggered 'vasovagal' reflex may unmask pre-existing mild to moderate structural abnormalities of the AV conduction system.

Electrophysiologic effects of procainamide, mexiletine, and amiodarone on the transplanted heart: Experimental study

The effects of procainamide, mexiletine, and amiodarone on automaticity, conduction, and refractoriness were studied in a model of heterotopic heart transplantation in dogs that combined an innervated heart (recipient) and a denervated transplanted heart (donor). After the surgical procedure, 500 mg procainamide ( n = 13), 200 mg plus 0.1 mg/kg per minute mexiletine ( n = 10), or 150 mg amiodarone ( n = 10) was administered intravenously. During a baseline period and after drug administration, each heart was assessed for atrioventricular interval; cycle length; sinoatrial conduction time; atrioventricular node anterograde and retrograde block points; atrioventricular node and ventricular antegrade effective refractory periods; PR, QRS, and QT intervals on electrocardiogram; systemic arterial, pulmonary arterial, central venous, and pulmonary capillary wedge pressures; and cardiac output. In recipients, procainamide reduced cardiac output, depressed sinus automaticity, slowed conduction time without affecting the QRS interval, and prolonged the nodal and ventricular refractoriness; in donor hearts, it depressed automaticity and prolonged nodal refractoriness, but did not modify conduction or ventricular refractoriness. Mexiletine only moderately depressed sinus automaticity in recipient hearts; it did not affect the other parameters either in recipient or transplanted hearts, nor did it alter the hemodynamic situation. Amiodarone produced hypotension, reduced cardiac output, and prolonged all the electrophysiologic intervals except the QRS interval in recipient hearts. These changes were even more pronounced in the transplanted hearts and led to extreme sinus bradycardia in four cases. Of these three drugs, mexiletine appears to be the safest should treatment for arrhythmias be necessary in transplant recipients. (J T HORAC C ARDIOVASC S URG 1995;109:899-904)

991-71 Electrophysiologic Findings in Patients with Obstructive Sleep Apnea Associated Ventricular Asystole

Fourteen patients (47 ± 11 years) with ventricular asystole of 5.6 ± 2.7 sec (range: 3.1–13.6 sec) due to complete atrioventricular (AV) block (n = 8), sinoatrial (SA) block or sinus node (SN) arrest (n = 5) or both (n = 1) occurring exclusively during sleep apnea episodes as documented by cardiorespiratory polysomnography underwent conventional electrophysiologic study: evaluation of sinus node function included rate corrected SN recovery time (CSNRT), sinoatrial conduction time (SACT, Narula method), and sinus rate (SR) response to atropine (0.02 mg/kg). CSNRT of &lt;550 ms, SACT of &lt;125 ms, and SR increase after atropin to &gt;90 bpm were considered to be normal. Assessment of AV-conduction included AH- and HV-intervals. AV-Wenckebach periods, and AV nodal effective refractory periods (ERPs) before and after atropine. None of the 14 pts received digitalis, beta-blockers or verapamil during polysomnography or EP study. 6 pts (42%) had hypertensive heart disease, 1 pt (8%) had coronary disease, and 7 pts (50%) showed no evidence of structural heart disease. SN function was normal in 12 of 14 pts (86%). Two pts had slightly prolonged SACTs (160 and 165 ms respectively). CSNRT and SR response to atropine was normal in all pts. AV nodal function was normal in 8 of 14 pts (57%) and abnormal in 4 pts (43%): 2 pts had prolonged AH-intervals of 135 and 143 ms, and 2 pts had AV-Wenckebach points at 520 and 730 ms and AV nodal ERPs of 500 and 700 ms respectively. AV-nodal function normalized after administration of atropine in all 4 pts. His-Purkinje system function was normal in 8 pts (57%), and 6 pts (43%) had slightly prolonged HV-Intervals (range: 59–63 ms). Intra- or infra His block was not observed in any pt. In conclusion , normal or only slightly abnormal electrophysiologic findings in most patients with sleep apnea associated ventricular asystole support the hypothesis that ventricular asystole is due to a neurally mediated cardioinhibitory reflex. However, it remains unsolved, why sleep apnea associated prolonged ventricular asystole does occur in some pts and does not occur in other pts despite severe obstructive sleep apnea.

912-43 Sick Sinus Syndrome. A Cardiac or a Neurocardiogenic Disorder?

The commonly proposed mechanism of syncope in patients (pts) with sick sinus syndrome (SSS) is a long sinus pause without an effective escape rhythm. Nevertheless, the probability of a coexistent neurally mediated syncope (NMS) component has not been adequatelly investigated in these pts. We studied 3 groups: Gl: 12 syncopal pts (age: 58 ± 12 years, M/F: 9/3) with SSS (unexplained sinus bradycardia with inadequate chronotropic response to exercise or atropine, long sinus node recovery or sinoatrial conduction times and low intrinsic heart rate), G2; 52 pts (37 ± 17 years, M/F; 18/12) with syncope of unknown etiology and G3: 20 healthy controls (HC) (34 ± 9 years, M/F: 16/4). The same tilt table test (TTT) protocol was used (20 min in 80° upright followed by three 10 min stages in the same position under graded isoproterenol intravenous infusion at 1 – 3μg/min). TTT was considered positive (pos) if induced pre or syncope due to hypotension with or without bradycardia. A pos TTT was observed in 7 Gl pts (58.3%) and 30 G2 pts (57.7%) (p: NS). In contrast, only 4 of the G3 HC (20%) developed syncope (p &lt; 0.005). The mean pos TTT duration was similar in both pts with SSS and pts with NMS (57 ± 18 vs 55 ± 17 min, p: NS). The mean posm duration was longer in the 4 HC with an induced vagotonic reaction when compared to the 30 NMS pts of G2168 ± 10 vs 55 ± 17 min, p &lt; 0.05). We conclude that syncopal SSS pts commonly demonstrate a pos TTT. This might explain the occasional failure to avoid recurrence of syncope in SSS pts treated with cardiac pacing.

798-6 Acute Effects of Zatebradine on Cardiac Conduction and Repolarization in Anesthetized Dogs

Zatebradine, a potent bradycardic agent, is believed to act selectively at the sinoatrial node. However, the selectivity of such an action relative to various electrophysiologic classes of action is not well defined. To characterize tie electrophysiologic properties of zatebradine, the corrected sinus node recovery time (SNRT/sinus cycle length), sinoatrial conduction time (SACT), conduction intervals, effective refractory period in atrium (AERP) and monophasic action potential duration (APD 90 ) in ventricle were measured before (Ctrl) and after administration of incremental doses of zatebradine (Zat, 0.1–1.5 mg/kg) in 15 anesthetized dogs. The effects of zatebradine on various electrophysiologic parameters could be observed immediately after a single i.v. bolus and reached steady-state at 15 min. (Mean ± S.D.): HR SNRTc SACT (ms) P-A (ms) A-H (ms) H-V (ms) P (ms) P-R (ms) QRS (ms) QTc (ms) AERP(ms) VAPD 90 (ms) Ctrl 78 1.28 130 20 135 68 68 187 115 501 175 413 ±8 ±0.2 ±20 ±2 ±19 ±8 ±9 ±12 ±31 ±33 ±10 ±16 Zat 43 2.27 140 20 178 70 70 235 122 553 260 562 ±9 ±0.3 ±29 ±2 ±24 ±8 ±9 ±13 ±32 ±35 ±14 ±15 p &lt;0.01 &lt;0.001 NS NS &lt;0.01 NS NS &lt;0.01 NS &lt;0.01 &lt;0.01 &lt;0.01 ED 50 0.23 0.22 – – 0.58 – – 0.57 – 0.76 0.60 0.78 (mg/kg) At low dose, Zat has a depressant effect on sinus nodal function; at higher doses, it has additional actions on A-V nodal function and lengthens repolarization reflecting effects on other ion channels.

A mathematical model of sinus node function: validation by recording of sinus node electrograms.

We have applied a mathematical function to model sinus node recovery after atrial pacing at different cycle lengths in 13 autonomically denervated, anesthetized canines. This model provides "pure" indexes of sinoatrial conduction and of suppression of automaticity. We compared sinoatrial conduction computed from the model (SACTc) with sinoatrial conduction measured directly utilizing a catheter recording the sinus node electrogram (SACTd) to test the validity of the model. We used both the model and the sinus node electrogram to further define events after pacing. There was close agreement between SACTc and SACTd with correlation coefficients at pacing cycle lengths of 20 and 50% below resting of 0.86 (P < 0.0001) and 0.78 (P < 0.0001), respectively. We verified that the conventional sinus node recovery time is due both to suppression of automaticity and prolongation of sinoatrial conduction. Sinoatrial conduction time returned rapidly to normal over 1-3 beats, whereas automaticity recovered exponentially over 20-40 postpacing intervals. The model accurately describes postpacing phenomena and has the potential to provide a useful adjunct to the measurement of the sinus node electrogram for assessment of sinus node function in the experimental laboratory.

Electrophysiology of the ageing rabbit and cat sinoatrial node -- a comparative study

Intrinsic properties of the human sinoatrial (SA) node have been shown to decline with age. In the present study we aimed at investigating the underlying mechanisms of age-dependent changes in intrinsic cycle length and sinoatrial conduction time. To this end, the cycle length and transmembrane potentials of the SA nodes of rabbits (2 days-5.6 years) and cats (6 weeks-18 years) were recorded and nodal conduction was reconstructed. The size of the SA nodes was measured in Sirius Red stained sections. Cycle length increases with age in both the rabbit and cat SA node, and in both species cycle length is dependent on diastolic depolarization rate and action potential duration. Nodal action potential duration increases with age in both rabbit and cat, whereas diastolic depolarization rate decreases in the cat only. The location of the primary pacemaker is not related to age. With age, sinoatrial conduction time increases in both species as a result of an enlargement of the area with low phase 0 upstroke velocities. The size of the SA node of adult animals does not increase with age.

Electrophysiological abnormalities before and after surgery for atrial septal defect

The authors evaluated the electrophysiological parameters, atrial-His interval, His-ventricular interval, Wenckebach cycle length, corrected sinus node recovery time (CSNRT), and sinoatrial conduction time (SACT) before and after operation in 28 children with atrial septal defect (ASD). Before operation, electrophysiological abnormalities were detected in 20 (79%) of the 28 patients. Preoperative comparison of the mean value in each parameter between the two age groups showed higher values in all parameters in the older group. In 17 patients who underwent operation, atrial-His interval, Wenckebach cycle length, CSNRT, and atrial effective refractory period (AERP) significantly decreased after operation; preoperatively abnormal Wenckebach cycle length, CSNRT, and AERP values were normalized in many of them. Thus, electrophysiological abnormalities were already present before operation in the ASD children and were severer in the older children, but were improved to some degree following operation.

Role of vagotony in sinus node dysfunction in children with symptomatic congenital long QT syndrome

The present study examined chronotropic dysfunction and the role of vagotony in congenital long QT syndrome, sinus node function and the effects of parasympathetic blockade. Six patients with congenital long QT syndrome were studied. The four males and two females, aged 1-15 years, had episodes of syncope and malignant ventricular arrhythmias. Congenital long QT syndrome was defined as a corrected QT interval greater than 0.45 s, T wave alternans and the age at diagnosis. The sinus heart rate measured from a 24 h electrocardiograph was abnormally low (< 50 min) in three patients (1, 4 and 5 years old) and did not increase sufficiently with the administration of atropine in five of the six patients with congenital long QT syndrome. From intracardiac electrophysiological studies, the corrected sinus node recovery time was prolonged in three patients and the total sinoatrial conduction time was prolonged in two patients. In most patients who had an abnormally long sinoatrial conduction time and corrected sinus node recovery time, these values returned to normal following atropine administration. In one patient, the corrected sinus node recovery time was prolonged paradoxically by atropine. Sinus node dysfunction in congenital long QT syndrome was affected by vagotony associated with a right sympathetic nerve system abnormality.

Age-related changes of sinus node function and autonomic regulation in subjects without sinus node disease--assessment by pharmacologic autonomic blockade.

To assess the relationship between aging and autonomic regulation of sinus node function, 56 subjects of various ages (range 14-75 years, mean 43 +/- 19 years) without sinus node disease were studied. Heart rate, corrected sinus node recovery time and sinoatrial conduction time were measured before (basic) and after (intrinsic) pharmacologic autonomic blockade (propranolol + atropine i.v.). Percent chronotropies of the above parameters were calculated by a modified Jordan's method. Basic heart rate and basic corrected sinus node recovery time did not vary with age (r = -0.15, r = 0.08, respectively), while basic sinoatrial conduction time tended to increase with age (r = 0.32, p < 0.05). Intrinsic heart rate decreased (r = -0.76, p < 0.001), and intrinsic corrected sinus node recovery time and intrinsic sinoatrial conduction time both increased with age (r = 0.55, p < 0.001; r = 0.56, p < 0.001, respectively). The younger the subject, the more negative the percent chronotropies of the above parameters were, and the percent chronotropies correlated positively with age (r = 0.68, p < 0.001; r = 0.52, p < 0.001 and r = 0.34, p < 0.05, respectively). In conclusion, intrinsic sinus node functions deteriorated with age. Furthermore, parasympathetic tone on the sinus node functions decreased with age, which may compensate for age-related deterioration of intrinsic sinus node function.

Acute and chronic electrophysiological effects of pentisomide on the sinus and AV nodal function, noninvasive evaluation by a pacemaker with temporary pacing inhibition.

The acute and chronic electrophysiological effects on sinus function and AV nodal conduction of pentisomide (Pen), a new antiarrhythmic agent, were studied in ten patients with sick sinus syndrome (SSS) (group I) and in ten patients with normal sinus function (group II) using a permanent pacemaker with temporary pacing inhibition (Symbios 7005 Medtronic, Inc.). We measured noninvasively the corrected sinus node recovery time (CSNRT), the sino-atrial conduction time (SACT), according to Narula's method and the Wenckebach point before and after Pen administration, acutely and orally for 10 days. In group I intravenous injection (4 mg/kg) and oral administration (450 mg bid) of Pen significantly prolonged the CSNRT (+217% and +149%, respectively) and the SACT (+63% and +49%, respectively). In group II only the intravenous injection of Pen provoked a significant modification of CSNRT (+12%) and SACT (+14%). No modification in AV nodal conduction was noted in any patient. These results suggest that Pen must be used with caution in patients with sinus nodal dysfunction.

Effect of fentanyl on cardiac automaticity and conduction: direct or mediated action?

The effects of fentanyl at a dose of 100 micrograms.kg-1 on cardiac automaticity, refractoriness and conduction have been studied in a model of heterotopic heart transplantation which combines a denervated heart (donor) and a non-denervated heart (recipient) in each of 20 dogs employed. Once the surgical procedure had been completed, cycle length, sinoatrial conduction time, antegrade and retrograde A-V node block points, cycle length at which 1:1 conduction ceases to exist and the antegrade effective refractory period of the A-V node and ventricles were measured. These parameters were determined in hearts both in the basal situation and 10 min after fentanyl injection. In the recipient organs, fentanyl produced statistically significant prolongation of cycle length, sinoatrial conduction time, antegrade block point and antegrade effective refractory periods of the A-V node and ventricles, with respect to the basal situation (P less than 0.01 for all these parameters); in 20% of cases, a complete A-V block was produced. In the donor hearts (denervated), prolongations of cycle length (P less than 0.01) and the antegrade block point (P less than 0.05), as compared with the basal situation, were recorded, but no other modifications were detected. To test whether these effects were due to the action of fentanyl, 10 animals were subsequently injected with naloxone, an agent which reverted the reported changes, although in the recipient organs, there persisted a slight prolongation of the cycle length with respect to basal measurements (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Sinus node function in hyperthyroid patients.

We have studied the electrophysiology of the sinus node and the role of the autonomic nervous system on sinus node function in 8 thyrotoxic patients of both sexes, 37.5 +/- 4.3 (mean +/- SE) yr old. The resting heart rate (RHR), the sino-atrial conduction time (SACT), and the sinus node recovery time (SNRT) were measured in the untreated condition (basal), after sympathetic blockade with propranolol 0.2 mg/kg body weight (BW) i.v. infusion, and after complete autonomic blockade with the additional administration of atropine 0.04 mg/kg BW i.v. bolus. 1) In the thyrotoxic patients the RHR was higher [117 +/- 6 beats per min (bpm)] than in 20 normal subjects (73 +/- 1 bpm, P less than 0.001), whereas the SACT and SNRT values were not different. 2) After sympathetic blockade with propranolol, the RHR decrement and SACT increase were greater in the hyperthyroid patients than in normal subjects, whereas there was no difference in SNRT values between the two groups. 3) In the thyrotoxic patients the complete autonomic blockade reestablished the electrophysiological parameters to values similar to those observed in basal condition. In conclusion, in thyrotoxic patients the intrinsic activity of the sinus node is increased. It appears that this is a direct consequence of thyroid hormone excess, rather than an effect of extrinsic influences exerted by the autonomic nervous system on sinus node activity.

Electrophysiological effects of atracurium and vecuronium on normal and denervated hearts

Atracurium and vecuronium offer some advantages with respect to other nondepolarizing muscule relaxants. However, their administration has been associated with episodes of bradycardia and asystole, the mechanism of which has not yet been clarified. In an effort to analyze the effects of these drugs on automaticity, refractoriness, and conduction, 30 dogs underwent heterotopic heart transplantation to establish a model in which a normal heart (recipient) and a denervated heart (donor) could coexist. The electrophysiological studies included the determination of cycle length (CL), sinoatrial conduction time (SACT), antegrade and retrograde atrio-ventricular (A-V) node and ventricular block points (ABP and RBP), as well as effective antegrade and retrograde A-V node (ARPAVN and RRPAVN) and ventricular refractory periods (VRPs) in both hearts. These parameters were measured in a basal state and after injection of pancuronium (0.5 mg/kg) in 10 animals, atracurium (0.5 mg/kg) in another 10 dogs, and vecuronium (0.12 mg/ kg) in the remaining animals. The results showed that pancuronium produced a tachycardia, significantly facilitated AN conduction in the donor and the recipient hearts, and lowered the AN node refractoriness in the donor organ, while atracurium and vecuronium induced no changes from the baseline values, either in normal or denervated hearts. Based on the results of this study, the episodes of sustained bradycardia reported in association with atracurium and vecuronium are attributed to the absence of antagonism of vagal stimuli provoked by pancuronium, and/or by surgical or anesthetic manipulations.

Postextrasystolic sinoatrial exit block in human sick sinus syndrome: Demonstration by direct recording of sinus node electrograms

Ten patients with sick sinus syndrome having repetitive sinus node electrograms during long postpacing pauses were studied during programmed atrial stimulation. Sinus node activity was recorded using a percutaneous catheter electrode. A sinus node electrogram was recorded before the return atrial beat in seven patients; it was similar to the sinus node electrogram observed during postpacing pauses and is clearly identified because sinoatrial conduction time was markedly prolonged following the atrial extra beat. Complete sinoatrial exit block occurred in four patients. (1) Sinus node electrograms were thus validated both during postpacing pauses and during programmed atrial stimulation in most patients with sick sinus syndrome. (2) Sinoatrial conduction time was markedly prolonged after one extrasystole, accounting for supracompensatory atrial return cycles. (3) If it were cumulative following multiple extrasystoles, this effect could constitute the electrophysiologic link between an abnormal response during programmed atrial stimulation and the complete sinoatrial block recorded during the pauses that follow rapid atrial pacing.