Improved sinus node sensing after atropine.

Although atropine is known to increase sinus rate through its vagolytic effect, the effects of atropine on sinus node sensing are unknown. The purpose of this study was to investigate alterations in sinus node sensing produced by atropine. Measurement of the zone of sinus node reset and sinoatrial conduction time was performed in 10 patients by programmed premature atrial stimulation. The zone of sinus node reset was determined as the transition point where premature atrial stimuli were followed by a less than compensatory pause. Sinoatrial conduction time was calculated from sinus node return cycles in the area where sinus node reset occurred. Atropine administration produced a significant increase in the percentage of the sinus cycle length at which premature atrial contractions penetrated and reset the sinus node. Sinus node reset occurred at a mean percentage of the sinus cycle of 71 +/- 8 per cent before atropine and 83 +/- 5 per cent after atropine (P less 0.01). The sinoatrial conduction time was significantly reduced from 109 +/- 29 to 62 +/- 23 msec. (P less than 0.01) from atropine as sinus cycle length was reduced from 909 +/- 118 to 642 +/- 75 msec. after atropine. Sinus node echoes were observed in two patients. In one patient atropine abolished the appearance of sinus node echoes. In the second patient atropine reduced the coupling interval necessary to produce sinus node echoes but appeared to facilitate sinus node re-entry by the appearance of an additional sinus node echo and a reduction in the echo cycle length. This study demonstrates that atropine produces significant improvement of sinus node sensing in man.     

Sinus nodal function in the intact dog heart evaluated by premature atrial stimulation and atrial pacing

Sinus nodal function was analyzed in 25 dogs by premature stimulation of the right atrium. The return (A_T-A_R) and post-return (A_R-A) cycles were plotted as a function of the premature cycle, and four zones were identified. Zone I (compensatory zone) was observed during the last 4.8 percent (mean value) of the sinus cycle (A-A). Zone II was observed during 43.6 to 95.2 percent (mean value) of the sinus cycle. During the latter part of zone II, A_T-A_R was nearly constant and A_R-A remained nearly equal to A-A during the last 29 percent (mean value) of the cycle. Earlier in zone II three distinct patterns of return cycle responses were observed whereas post-return cycles either remained nearly equal to A-A or showed progressive lengthening. Zone III (interpolation) was observed in 10 animals during 39.5 to 46.2 percent (mean value) of the sinus cycle. A_R-A was nearly equal to A-A in zone III. Interpolation was incomplete late and complete early in the zone. Zone IV (echo zone) was seen in another 10 animals during 40.9 to 45.3 percent (mean value) of the sinus cycle and in this zone A_R-A was greater than A-A. No significant difference in these zones was seen among the animals anesthetized with pentobarbital or alpha-chloralose, or given 6-OH-dopamine. The A_R-A was important in the analysis of these zones and appears to be essential to the interpretation of data derived from premature atrial stimulation. Responses to premature atrial stimulation through a catheter electrode positioned against the sinus nodal region compared favorably with responses to direct epicardial stimulation. After periods of continuous right atrial pacing a variety of patterns of sinus nodal depression were observed at different rates and durations of stimulation. The frequent occurrence of a short sinus escape cycle followed by the maximal pause observed during rapid pacing rates suggests sinus nodal entrance block. This may be an important factor to consider in determining an optimal pacing rate for assessing sinus nodal function.     

Electrophysiologic effects of atropine on human sinus node and atrium.

Electrophysiologic studies were conducted in 17 patients without apparent sinus node disease before and after intravenous administration of 1 to 2 mg of atropine. Mean values in milliseconds (+/- standard error of the mean) before and after administration of atropine were as follows: sinus cycle length 846 +/- 26.4 versus 647 +/- 20.0 (P less than 0.001); sinus nodal recovery time 1,029 +/- 37 versus 774 +/- 36 (P less than 0.001); mean calculated sinoatrial (S-A) conduction time 103 +/- 5.7 versus 58 +/- 3.9 (P less than 0.001); mean P-A interval 34 +/- 1.5 msec versus 31 +/- 1.5 (P less than 0.05); mean atrial effective and functional refractory periods during sinus rhythm 285 +/- 11.3 versus 238 +/- 7.9 and 331 +/0 11.6 versus 280 +/- 8.6, respectively (P less than 0.001 for both); mean atrial effective and functional refractory periods measured at equivalent driven cycle length 239 +/- 7.7 versus 213 +/- 7.4 and 277 +/- 11.4 versus 245 +/- 9.5, respectively (P less than 0.001 for both). In conclusion, atropine shortened sinus cycle length, sinus nodal recovery time and calculated S-A conduction time. The shortening of atrial refractory periods with atropine implies that vagotonia prolongs atrial refractoriness in man.     

Predicting ventricular tachycardia cycle length after procainamide by assessing cycle length-dependent changes in paced QRS duration

To determine if paced cycle length-dependent changes in the QRS duration correlate with the change in ventricular tachycardia (VT) cycle length after procainamide, we measured the QRS duration during sinus rhythm and during right ventricular pacing before and after procainamide (mean concentration, 9.9 micrograms/ml) in 18 patients with morphologically identical VT induced at both study periods. Pacing was performed at 600 msec or the longest cycle length that allowed for uninterrupted capture and at a cycle length that was within 50 msec of the VT cycle length observed during the control study (mean, 313 +/- 51 msec). After procainamide, the VT cycle length increased from 285 +/- 62 to 368 +/- 70 msec (percent change, 30 +/- 13%). The QRS duration during sinus rhythm increased from 125 +/- 25 to 145 +/- 29 msec (percent change, 16%). The QRS duration at both paced cycle lengths was the same in the baseline state (191 +/- 26 msec). However, the change in QRS duration after procainamide at the shorter paced cycle length compared to a 39 +/- 13 msec (18%) increase at the longer paced cycle, p less than 0.001. There was a significant correlation between the percent change in QRS duration at the shorter paced cycle length and the percent change in VT cycle length (r = 0.84, p less than 0.001) with the relation expressed by the regression equation: percent change in VT cycle length = -2.8 + 1.16 x percent change in QRS duration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrophysiologic effects of atropine on sinus node and atrium in patients with sinus nodal dysfunction

Electrophysiologic studies were conducted in 21 patients with sinus nodal dysfunction before and after intravenous administration of 1 to 2 mg of atropine. The mean sinus cycle length (± standard error of the mean) was 1,171 ± 35 msec before and 806 ± 29 msec after administration of atropine (P < 0.001). Mean sinus nodal recovery time determined at a paced rate of 130/min and maximal recovery time were, respectively, 1,426 ± 75 and 1,690 ± 100 msec before and 1,169 ± 90 and 1,311 ± 111 msec after atropine (P < 0.001 and < 0.001). Mean calculated sinoatrial conduction time, measured in 16 patients, was 113 ± 8 msec before and 105 ± 9.7 msec after atropine (difference not significant). Mean atrial effective refractory period, measured at an equivalent driven cycle length, was 262 ± 11.1 msec before and 256 ± 10.3 msec after atropine (not significant). Mean atrial functional refractory period was 302 ± 12.5 msec before and 295 ± 11.3 msec after atropine (not significant).

The shortening of sinus cycle length and sinus recovery time with atropine was similar to that noted in patients without sinus nodal dysfunction. In contrast, atropine had insignificant effects on sinoatrial conduction and atrial refractoriness in this group whereas it shortens both in normal subjects. This finding may reflect altered perinodal and atrial electrophysiologic properties in patients with sinus node disease.     

Rate dependent variation in concealed bigeminy

A 63 year old man with angina pectoris was found to have frequent extrasystoles separated by odd as well as even numbers of conducted sinus beats. Analysis of 935 conducted sinus beats showed that premature ventricular beats without interpolation were separated by odd numbers of conducted sinus beats in 117 sequences and even numbers (exceptions) in 48 sequences (p less than 2 X 10(-4)). Tabulation of cycle lengths revealed that cycles with even numbers of conducted sinus beats were characterized by a significant reduction in the preceding postextrasystolic pause (1441+/-76 msec vs. 1487 +/-59 msec; p less than .001) and second sinus cycle (720 +/- 44 msec vs. 750 +/- 38 msec; p less than .001). Premature ventricular beats were interpolated in 41 additional sequences. Interpolated extrasystoles were separated by the expected even numbers of conducted sinus beats in 39 cases and odd numbers (exceptions) in only two cases. The frequency of exceptions to the usual rules for concealed bigeminy was therefore 2/39 during interpolation and 48/117 without interpolation (p less than .01). This case demonstrates that: 1) a reduction in cycle length may be associated with exceptions to the usual rules for concealed bigeminy, and 2) the frequency of exceptions to concealed bigeminy may be altered by the presence of interpolation. Only one previous case has contained statistical documentation of these circumstances. The diagnosis of a concealed ventricular rhythm may be facilitated by careful analysis at multiple cycle lengths.     

Effects of cycle length on atrial vulnerability.

The effect of cycle length on atrial vulnerability was studied in 14 patients manifesting reproducible repetitive atrial firing during atrial extra-stimulus (A2) testing. Repetitive atrial firing was defined as the occurrence of two or more premature atrial responses with return cycle (A2-A3) of 250 msec or less and subsequent mean cycle length of 300 msec or less, following A2. The zone of repetitive atrial firing could be defined in terms of its longest and shortest A1-A2 coupling intervals. Each patient was tested at a long cycle length (CL1) (mean 884 msec) and a short cycle length (CL2) (mean 557 msec). CL1 was sinus rhythm and CL2, an atrial paced rhythm. Repetitive atrial firing occurred in two patients at CL1 and in all patients at CL2. Of the former two patients (group 2), the zone of repetitive atrial firing was markedly widened in one at CL2 due to a shortening of atrial functional refractory period (FRP) at CL2. In the other, zone of repetitive atrial firing could not be totally defined due to induction of sustained atrial flutter preventing definition of atrial FRP. The occurrence of repetitive atrial firing at only CL2 in 12 patients (group 1) reflected: 1) a shortening of atrial FRP from 294 +/- 11 msec at CL1 to 242 +/- 10 msec at CL2 (mean +/- SEM; P less than 0.01), allowing delivery of A2 at shorter coupling intervals (9); 2) the new occurrence of repetitive atrial firing at A1-A2 coupling intervals achievable at both cycle lengths (1); or 3) both effects (2). In conclusion, decrease of cycle length potentiated atrial vulnerability. This demonstration implies that atrial pacing could potentiate occurrence of paroxysmal atrial fibrillation or flutter.     

The measurement of sinus node refractoriness in man

We recently described a method for measuring sinus node refractoriness in the rabbit heart. Atrial premature beats either may result in reset return responses or may become interpolated because of encroachment on sinus node refractoriness. In previous studies with rabbits we defined the effective refractory period of the sinus node (SNERP) as the longest premature interval that is interpolated. This study presents results on the extension of this technique to the measurement of sinus node refractoriness in man. Out of 30 patients (12 with and 18 without sinus node dysfunction), SNERP could be measured in 26 at one or more basic cycle lengths. At a basic pacing cycle length of 600 msec, SNERP ranged from 250 to 380 msec (mean 325 +/- 39) in patients without sinus node dysfunction and from 500 to 550 msec (mean 522 +/- 20) in patients with sinus node dysfunction. This clear differentiation of patients with and without sinus node dysfunction by SNERP is in contrast to various results obtained by assessing sinus node function from sinus node recovery time and sinoatrial conduction time. Thus this study suggests the possible use of the measurement of SNERP in the assessment of sinus node function in man and its possible value in identifying patients with sinus node dysfunction.     

Differential effects of autonomic blockade on sinus and atrioventricular nodal function in normals and in intrinsic sinus node dysfunction

The effect of pharmacologic total autonomic blockade on sinus and atrioventricular nodes was studied in 10 normals and 21 patients with sick sinus syndrome with abnormal intrinsic corrected sinus node recovery time. In normals the intrinsic heart rate (113.3 +/- 11.6 beats/min) was higher than the resting heart rate (87.3 +/- 12 beats/min; P less than 0.001). The AH interval at an identical paced rate decreased from 119 +/- 36 msec to 93 +/- 17.6 msec after autonomic blockade (P less than 0.05). Mean atrial paced cycle length at AH Wenckebach block was not different during control and after drugs (319 +/- 46 msec vs. 311.5 +/- 39 msec; P = NS). Although sinus cycle length shortened in all cases after autonomic blockade, paced cycle length at AH Wenckebach increased (4) or remained unchanged (3) in 7 cases. Maximum normal "intrinsic" paced cycle length at AH Wenckebach was 390 msec (mean +/- 2 SD). In sick sinus syndrome, resting heart rate (66.3 +/- 18.8 beats/min) and intrinsic heart rate (74.6 +/- 16.4 beats/min) were similar (P = NS); AH at identical paced rate: control 136.6 +/- 54 msec, after drugs 130.5 +/- 35 msec (P = NS); cycle length at AH Wenckebach: control 380.5 +/- 73 msec, after autonomic blockade 383 +/- 49 msec (P = NS). Two of 3 cases with abnormal atrioventricular nodal response to atrial pacing during control normalized after autonomic blockade; 9/21 (42.8%) cases developed AH Wenckebach at cycle length greater than 390 msec after autonomic blockade. The data suggest that the autonomic nervous system has differential effects on sinus and atrioventricular nodes. Patients with sick sinus syndrome frequently have abnormalities of "intrinsic" atrioventricular nodal conduction unmasked by autonomic blockade.     

Electrophysiologic evaluation of sinus node function in patients with sinus node dysfunction.

Twenty patients of mean age 66.2 years, with suspected sinus node dysfunction, underwent extensive electrophysiologic study. Sinus bradycardia (18), sinus pauses (3), and sinoatrial block (1) were identified in their ECGs prior to study. Also 11 patients had some abnormality of atrioventricular nodal and/or intraventricular conduction prior to study. At the time of electrophysiological study, 10/20 patients (50%) had a mean cycle length exceeding 1000 msec, and mean P-V interval exceeded 210 msec in 7/20 (35%). The estimated "sinoatrial conduction time" exceeded 215 msec in 6/16 (38%) patients. The maximum first escape cycle following pacing at six different rates exceeded a value equal 1.3 X the mean value of the control cycle length + 101 msec (slope of regression line + Y intercept + 1 SD) in 13/9 (68%) patients. Nineteen patients received 1 mg atropine intravenously and mean cycle length decreased by 19%, from 891 +/- 175.8 msec to 718 +/- 182.9 msec. Graded infusion of isoproterenol was employed in 19 patients; four patients required an infusion rate greater than 28.3 ng/kg/min to produce a 20% decrease in spontaneous sinus cycle length. These data would indicate that a variety of interventions are required to characterize the disturbance of sinus node automaticiy and sinoatrial conduction in patients with sinus node dysfunction.     

Sinus nodal echoes. Clinical case report and canine studies

Sinus nodal echoes are illustrated in (1) a case report, and (2) a study of the effects of atrial premature beats after atrial drive in dogs. When atrial premature beats confront the sinus node while it is still refractory, 3 types of response may be seen: (1) Complete interpolation—the subsequent sinus beat (or escape) comes precisely at the expected time; (2) incomplete interpolation—the subsequent sinus beat is delayed; and (3) sinus echoes—the sinus beat appears earlier than expected. In all 3 instances the node is entered, but the pacemaker fails to be reset. Although the echo has the form of a sinus beat, it is followed by a pause, presumably as a result of repenetration of the sinus node through pathways unused during exit. The curves characterizing the expansion by vagal stimulation of the nodal refractory period and total echo circuit time are defined, together with the latency of cholinergic effect on nodal refractoriness, sinus automaticity and exit conduction of the echo. The secondary concealment zone of a completely interpolated atrial premature beat is established. Atrial preexcitation (before the echo) sometimes evokes a second echo. The limiting factor on sustained sinoatrial reciprocation thus appears to be total echo circuit time rather than refractoriness of atrium or echo entrance pathways. The repetitive echoes seen in this study may be the basis for some clinical cases of sinus or atrial tachycardia.     

Characterization of Sinoatrial Parasympathetic Innervation in Humans

INTRODUCTION: The response to sinoatrial parasympathetic nerve stimulation (shortened atrial refractoriness) was used to determine the atrial distribution of these nerve fibers in humans. We hypothesized that, in humans, parasympathetic nerves that innervate the sinoatrial node also innervate the right atrium and that the greatest density of innervation is near the sinoatrial nodal fat pad. METHODS AND RESULTS: Temporary epicardial wire electrodes were sutured in pairs in the sinoatrial nodal fat pad, high right atrium, and right ventricle by direct visualization during coronary artery bypass surgery in nine patients. Appropriate electrode placement was confirmed by electrically stimulating the fat pad in the operating room to prolong sinus cycle length by 50%. Experiments were performed in the electrophysiology laboratory 1 to 5 days after surgery. Programmed atrial stimulation was performed via an endocardial electrode catheter advanced to the right atrium. The catheter tip electrode was moved in 1-cm concentric zones around the epicardial wires by fluoroscopic guidance. Atrial refractoriness was determined in the presence and absence of sinoatrial parasympathetic nerve stimulation at each catheter site. In 8 of 9 patients, parasympathetic nerve stimulation reproducibly prolonged sinus cycle length by 50%. There was no effect on AV nodal conduction (no prolongation of PR interval) and no change in AV nodal refractoriness. Atrial effective refractory periods reproducibly shortened in response to parasympathetic nerve stimulation in 1-cm zones up to 3 cm surrounding the fat pad, by a mean (+/- SEM) of 26.6+/-4.3 msec (zone 1), 11.4+/-1.8 msec (zone 2), and 10.0+/-2.5 msec (zone 3), respectively (P = 0.0001). At distances > 3 cm from the fat pad, the effective refractory period did not shorten. CONCLUSION: Stimulation of parasympathetic nerves that innervate the sinoatrial node shortened atrial refractoriness in humans.     

Effect of glucagon on cardiac conduction in man

His bundle electrograms were obtained in 26 patients before and after intravenous administration of glucagon (50 μg/kg). The group consisted of 4 patients with normal conduction and 22 patients with conduction disease. The P-A interval, measured in all patients, was 35 ± 1.4 msec (mean ± standard error of the mean) before and 30 ± 1.5 msec after infusion of glucagon (P < 0.001). The mean A-H interval during sinus rhythm in all patients and during pacing at 100/min in 21 patients was, respectively, 97 ± 6.0 msec and 114 ± 6.4 msec before, and 96 ± 6.0 msec and 114 ± 6.6 msec after infusion of glucagon (not significant). The mean H-V interval in 25 patients was 48 ± 2.6 msec before and 49 ± 2.0 msec after infusion of glucagon (not significant). The mean sinus rate and sinus recovery times were, respectively, 73 ± 3.0 beats/min and 1,025 ± 42.0 msec before and 81 ± 3.0 beats/min and 919 ± 27.0 msec after infusion of glucagon (P < 0.001 and < 0.01). Functional and effective refractory periods were measured (In milliseconds) with use of the atrial extrastimulus technique. The mean atrial functional and effective refractory periods (21 patients) were, respectively, 273 ± 11.6 and 252 ± 12.0 before and 256 ± 10.0 and 238 ± 9.6 after infusion of glucagon (P < 0.001 and < 0.01). Mean atrloventricular (A-V) nodal functional refractory period (22 patients) and effective refractory period (15 patients) were 465 ± 22.0 and 404 ± 33.0 before and 457 ± 23.0 and 395 ± 32.0 after the infusion (not significant). The mean effective refractory period of the His-Purkinje system (2 patients) was 440 ± 45.0 before and 425 ± 55.0 after infusion of glucagon (not significant).In summary, glucagon increased sinus nodal automaticity, as manifested by an increase in sinus rate and decrease of sinus nodal recovery time, and improved intraatrial conduction as manifested by a reduction of the P-A interval and atrial functional and effective refractory periods. Glucagon had no effect on A-V nodal or intraventricular conduction.     

The effect of premature atrial depolarization on sinus node automaticity in man.

Sino-atrial conduction time (SACT) may be calculated from the difference between the length of the return cycle and the spontaneous cycle, using programmed premature atrial stimulation during spontaneous sinus rhythm. This approach to sinoatrial conduction assumes that sinus node automaticity is not changed by premature depolarization. In order to validate this assumption, we compared the length of the post-return cycles to the spontaneous cycle length in 71 patients. Patients were grouped according to clinical diagnosis and the value of calculated SACT. At long coupling intervals at which no reset of the sinus node occurred there was only a small prolongation of the post-return cycles (less than 8.4 msec, on an average) compared to the spontaneous cycle length. This suggests no or only an insignificant effect of premature depolarization on the sinus node. However, during test stimuli leading to reset of the sinus node, the post-return cycles were significantly prolonged between 20 to 30 msec, on an average. The response of the individual cases sometimes varied to a great extent. In patients who demonstrated a progressive linear prolongation of the return cycles at decremental shortening of the test interval, there was no significant prolongation of the post-return cycles versus the spontaneous cycle length. We conclude that 1) premature depolarization of the sinus node may have a depressant effect on sinus node automaticity, which, if present, is usually small; 2) calculation of SACT using the extrastimulus technique may overestimate true SACT.     

Comparative study of two methods of estimating sinoatrial conduction time in man

Programmed premature atrial stimulation has been widely used to estimate sinoatrial conduction time in man. A proposed new approach uses continuous atrial pacing just above the spontaneous cycle length. Sinoatrial conduction time is represented by the difference between the first cycle after pacing and the spontaneous cycle length, assuming that sinus nodal automaticity is undisturbed by continuous atrial pacing.

Both techniques were compared in 23 consecutive patients. Mean (± standard deviation) sinoatrial conduction time was 113 ± 27 msec estimated with the premature stimulus technique and 96 ± 48 msec when estimated with the continuous pacing technique. In about 30 percent of cases the two values corresponded well with each other. In the remaining patients sinoatrial conduction time estimated with the premature stimulus technique was longer than the time estimated with continuous atrial pacing. Additionally, the latter was estimated at two different rates of pacing in which the cycle length was 30 and 60 msec, respectively, shorter than the previous cycle length. The estimate then increased to 119 ± 39 and 136 ± 40 msec, respectively. Sinoatrial conduction time estimated with continuous atrial pacing did not depend on spontaneous cycle length and did not correlate with sinus nodal recovery time. The cycles after the first pause were slightly longer than the spontaneous cycle length.

The results suggest that data from the two techniques cannot be easily compared and that premature atrial stimulation may exert a more depressive effect on sinus nodal automaticity than continuous atrial pacing. The observed differences in results may also be due to a more pronounced delay of retrograde conduction during premature atrial stimulation than during continuous atrial pacing. It is also possible that continuous atrial pacing leads to some overdrive exciting effect on the sinus node, although the opposite effect is suggested by the response of the cycles after the first postpacing cycle. A final conclusion regarding the validity of each technique cannot be reached on the basis of these clinical data.     

Electrophysiologic effects of intravenous timolol

We evaluated the electrophysiologic effects and dose response of the long-acting beta-blocking drug timolol given intravenously to 12 patients during intracardiac electrophysiologic study. Electrophysiologic parameters were measured during control and immediately, 30 minutes, and 48 hours following infusion. Significant changes in electrophysiologic parameters were only observed in the five patients (Group B) who received 0.05 mg/kg and not in the seven patients who received 0.02 mg/kg (Group A). In Group B patients immediately after timolol infusion sinus cycle length increased from 840 +/- 254 msec to 1048 +/- 63 msec (P less than 0.01), A-H interval during normal sinus rhythm increased from 94 +/- 42 msec to 101 +/- 45 msec (P less than 0.05), paced cycle length to A-V nodal Wenckebach increased from 370 +/- 45 msec to 430 +/- 76 msec (P less than 0.05), and A-V nodal effective refractory period increased from 284 +/- 63 msec to 360 +/- 83 msec (P less than 0.01). Significant increases in these electrophysiologic parameters were also noted at 30 minutes following timolol infusion. Other conduction times, atrial and ventricular refractory periods, and corrected sinus node recovery. time were unaltered by timolol. All electrophysiologic parameters returned to control in 48 hours. No adverse effects were observed. We conclude that intravenous timolol in doses of 0.05 mg/kg significantly increases sinus cycle length and prolongs A-V nodal conduction and refractoriness, demonstrates peak effects immediately after intravenous administration, and is well tolerated.     

The excitable gap in atrioventricular nodal reentrant tachycardia. Characterization with ventricular extrastimuli and pharmacologic intervention

Our purpose was to characterize the excitable gap during atrioventricular nodal reentrant tachycardia (AVNRT) to elucidate the electrophysiologic substrate of this clinically familiar microreentrant arrhythmia. Accordingly, in 11 patients with classic slow-fast AVNRT (mean cycle length, 342 +/- 41 msec), a single ventricular extrastimulus (V2) was periodically delivered after a spontaneous tachycardia beat (V1) until ventricular refractoriness was reached. With this technique, an excitable gap was considered present when atrial preexcitation of at least 20 msec could be achieved along with tachycardia resetting (noncompensatory pause after V2). The range of V1V2 intervals that resulted in atrial preexcitation constituted the preexcitation zone. Five patients (45%) showed evidence of an excitable gap at baseline, with a maximal atrial preexcitation achievable of 33 +/- 6 msec, representing 9 +/- 1% of the tachycardia cycle length. Verapamil was then administered to all 11 patients with the purpose of slowing the anterograde tachycardia wavefront before arrival of V2. This resulted in widening of the preexcitation zone in three patients by a mean of 50 +/- 37 msec, with a corresponding increase in maximal atrial preexcitation to 70 +/- 32 msec, or 16 +/- 4% of AVNRT cycle length, and the appearance of atrial preexcitation in two patients who lacked it during baseline. In the remaining six patients, AVNRT was not sustained after verapamil or was too unstable for evaluation. During baseline, V2A2 conduction time increased by only 5 +/- 3 msec throughout the preexcitation zone, with values at the outer border unchanged after verapamil, implying a fully excitable gap in the retrograde limb. In all patients with a preexcitation zone, AVNRT was consistently reset by V2, both at baseline and after verapamil, with a "flat" but mainly "increasing" response pattern as V1V2 was shortened. Hence, a significant number of patients with AVNRT have evidence of an excitable gap whose demonstrability can be facilitated by pharmacologic intervention; documentation of an increasing resetting response pattern, most apparent after verapamil, provides new evidence for a reentrant mechanism in AVNRT; and while not definitively proven, the presence of a fully excitable gap during AVNRT is most consistent with a microreentry circuit that incorporates an anatomic obstacle.     

Electrophysiologic effects of propranolol on sinus node function in children

Little is known regarding the effects of propranolol (P) on sinus node function in children. In this study, corrected sinus node recovery time (CSNRT) and estimated sinoartial conduction time (SACT) were measured in 10 children (ages 3 to 16 years; mean 8.3 years) without clinical evidence of sinus node dysfunction before and after intravenous P. The spontaneous sinus cycle length (SCL) increased after P(0.1 mg/kg) in all patients. Mean SCL increased 13.4% from 635 ± 200 msec (± SD) to 720 ± 202 msec (p < 0.01). Maximum CSNRT increased in nine patients after P and mean CSNRT increased 63% from 203 ± 61 msec to 330 ± 190 msec (p < 0.05). SACT changed in a random fashion after P. Mean SACT did not change significantly. We conclude that P significantly suppresses sinus node automaticity in children with normal sinus node function but has little or no effect on sinoatrial conduction.     

A new indirect method for measurement of sinoatrial conduction time and sinus node return cycle

We developed a new indirect method for the measurement of sinoatrial conduction time (SACT) and the sinus node return cycle (SRC) with a transvenous catheter technique. Two early premature stimuli, at intervals 50 msec longer than the effective refractory period (ERP), were given to the right atrium. These early stimuli were followed by eight constant stimuli. The interval of the constant stimuli was a little shorter than the basic cycle length (BCL). The return cycle A1Ar was measured and plotted on the abscissa; the next interval ArA3, was measured and plotted on the ordinate. This was called the "base point". A new stimulus, A2, was then added to the train of stimulations, first at a point simultaneous with Ar. It was then shifted toward the last constant stimulus at 10-20 msec intervals until A2 met the ERP. The relationship between A1A2 and A2A3 was obtained by the repetition of the procedures with various A1A2 intervals. It had two zones, compensatory and non-compensatory. We postulate that the atriosinus conduction time of the last of the eight stimuli was equal to that of A2 when the stimulus A2 first captured and reset the sinus nodal pacemaker cells, as indicated by the transition point of the two zones. Based on this supposition, SACT and SRC could be measured as the intervals from the base point to the transition point and from the transition point to the eighth stimulus, respectively.     

Comparison of individual and combined effects of procainamide and amiodarone in patients with sustained ventricular tachyarrhythmias

To compare the individual and combined electrophysiological effects of amiodarone and procainamide, 35 patients with sustained ventricular arrhythmias underwent programmed stimulation in the control state, after procainamide (mean concentration, 8.7 +/- 2.8 micrograms/ml), after 13 +/- 2 days of amiodarone (1,400 mg/day x 7 days, then 400 mg/day), and after amiodarone with procainamide (mean procainamide concentration, 7.8 +/- 2.2 micrograms/ml). Sustained ventricular tachycardia (VT) was inducible in all 35 patients during treatment with procainamide alone and with amiodarone alone. Procainamide and amiodarone similarly increased the VT cycle length (+68 vs. +61 msec), the corrected QT interval (+63 vs. +49 msec), and the ventricular effective refractory period measured at paced cycle lengths of 600-550 msec (+23 vs. +21 msec) and 400 msec (+25 vs. +23 msec). Procainamide had a more pronounced effect on QRS duration than amiodarone during sinus rhythm (+18 vs. +8 msec, p less than 0.01) and during paced cycle lengths of 600-550 msec (+32 vs. +23 msec, p less than 0.01) and 400 msec (+37 vs. +28 msec, p less than 0.1) but a similar effect on the QRS duration during VT (+32 vs. +29 msec). During combination therapy, VT initiation was prevented in only two (6%) patients. The combination therapy produced a greater increase (p less than 0.001) than individual therapy in all the electrophysiological intervals assessed, with the exception of the sinus cycle length. On each drug regimen, a cycle length-dependent increase (p less than 0.05) in paced QRS duration was noted (400 more than 600-550 msec).(ABSTRACT TRUNCATED AT 250 WORDS)