Corrected Sinus Node Recovery Time Research Articles

Electrophysiologic study of patients with ventricular dysrhythmias during long-term follow-up after repair of tetralogy of Fallot.

We performed an electrophysiologic study (EPS) in 8 patients who had received corrective surgery for tetralogy of Fallot. The mean age was 30 years. An average of 15 years had elapsed after corrective surgery. Two patients had episodes of syncope. ECG showed normal sinus rhythm in 7 patients and atrial fibrillation in 1, and all had complete right bundle branch block. All patients had ventricular premature beats of grade 3 or higher of Lown's classification. Overdrive suppression test was performed in 6 patients. Corrected sinus node recovery time (CSNRT) ranged from 230 msec to 510 msec. Wenckebach block of atrioventricular nodal conduction occurred at rates of 130 to 170 bpm during atrial pacing. The H-V interval was prolonged to 60 msec in 1 patient, but was below 55 msec in the others. Programmed stimulation induced ventricular tachycardia (VT) in 3 patients, nonsustained VT in 2 and sustained VT in 1. In 2 of 3 patients, delayed potential or fragmentations were recorded in the outflow tract of the right ventricle. During the follow-up period of 20 months, 2 patients died suddenly. Their CSNRTs and H-V intervals were normal. Ventricular tachyarrhythmia seems to be important as a cause of late sudden death after repair of tetralogy of Fallot.

Sinus node and atrioventricular nodal function in 220 patients recovering from acute myocardial infarction.

Sinus node and atriventricular (A-V) nodal functions were evaluated by right atrial pacing in 220 consecutive patients recovering from acute myocardial infarction (AMI), 10-28 days after the infarct (mean = 14 days). In the 188 patients in whom a pacing rate of 120 beats/min could be achieved, sinus node recovery time, corrected sinus node recovery time (CSNRT) and total recovery time were correlated to infarct site and the presence or absence of myocardial ischemia. Sinus node recovery time and total recovery time were significantly longer in patients with inferior (1,153 + 28 and 3,129 + 179 ms, respectively) or non-Q-wave infarct (1,112 + 28 and 3,730 + 266 ms, respectively), than in patients with anterior infarct (1,044 + 20 and 1,153 + 28 ms, respectively). The parameters were within the reported normal range. When corrected for heart rate (CSNRT), these differences were no longer present. The presence or site of residual ischemia during right atrial pacing did not affect the sinus nodes parameters. A-V nodal function, studied in all 220 patients, was assessed by the appearance of second-degree A-V block at pacing rates below 120 beats/min and by measuring the shortest atrially paced cycle length with 1:1 A-V conduction. Second-degree A-V block appeared at a similar frequency in different AMI locations. Thus, sinus and A-V node functional status in patients recovering from AMI are not affected by infarct site or by the presence or absence of residual myocardial ischemia.

Electrophysiological effects of propranolol in patients with sinus node dysfunction.

The electrophysiological effects of intravenous propranolol (0.15 mg/kg) were studied in 26 patients with sinus node dysfunction (SND group) and 9 patients with normal sinus node function (control group). Spontaneous cycle length and AH interval were significantly increased in the control and SND groups after propranolol. PA and HV intervals, calculated sinoatrial conduction time and refractory periods of the atrium, AV node and ventricle were not significantly changed in either group. Maximum corrected sinus node recovery time (max CSRT) was not changed in the control group, but it was significantly prolonged in the SND group. These results of the overdrive suppression test were in disagreement with those of previous studies. Propranolol lengthened spontaneous cycle length (by more than 200 msec) and/or max CSRT (by more than 1000 msec) in 8 of 26 patients with SND. Thus, it is suggested that propranolol should be used with caution in patients with SND.

Electrophysiological effects of bisoprolol.

The aim of this study was the electrophysiological evaluation of bisoprolol, a new highly cardioselective beta blocker, void of intrinsic sympathomimetic activity and without significant membrane stabilizing action. 10 patients (4 males and 6 females, mean age 67.5 years) with cardiac arrhythmias or syncopes of undetermined origin underwent His bundle recording with incremental as well as programmed atrial and ventricular pacing in an electrophysiological study. Electrophysiological parameters were measured at basal conditions and at 15 and 30 minutes after the infusion of bisoprolol 5 mg (for patient 1 to 5) and 10 mg (for patient 6 to 10). All electrophysiological parameters were within normal range at basal evaluation. Bisoprolol prolongs significantly sinus cycle length, corrected sinus node recovery time, AH interval, cycle length inducing AV-node block, effective and functional refractory periods of the AV-node. All these parameters remained within normal limits and were modified to about the same extent by 5 and 10 mg of the drug. No drug-related changes of QT interval were observed. Bisoprolol have been confirmed to have strictly beta-blocking properties.

Bedside evaluation of sinus bradycardia: Usefulness of atropine test in discriminating organic from autonomic involvement of sinus automaticity

In 55 patients with persistent sinus bradycardla who underwent an electrophysiologic study of sinus node, both in the basal state and after autonomic blockade (propranolol, 0.2 mg/kg, and atropine, 0.04 mg/kg), an atropine test (0.02 mg/kg) was performed the following day. The 49 patients in whom sinus rate could be evaluated after atropine were subdivided into two groups—group I, 24 patients (age: 54 ± 13 years) with normal intrinsic sinus automaticity (normal intrinsic heart rate and intrinsic corrected sinus node recovery time) and group II, 25 patients (age: 62 ± 9 years) with abnormal intrinsic sinus automaticity. In group I, atropine increased sinus rate from 53.7 ± 4 to 87.9 ± 17 bpm (Δ%: 65.5 ± 33) and in group II from 51.6 ± 5 to 73.9 ± 14 bpm (Δ%: 43.1 ± 26). The discriminant threshold of sinus rate after atropine and its percent increase, obtained by discriminant analysis, was 80 bpm and +52%, respectivoly, with a misleading classification of 32% and 36%, respectively. The overall predictive accuracy of sinus rate after atropine was higher than the percent change in sinus rate (73% and 65%, respectively). These data evidence that the atropine test is not very helpful in discriminating between an organic and an autonomic involvement of sinus automaticity in patients with sinus bradycardia.

Dissociation of electrophysiologic and pharmacologic stability during an abbreviated oral loading regimen of amiodarone

Thirty-three patients treated with an abbreviated oral amiodarone loading regimen for ventricular tachycardia underwent electrophysiologic testing in the control state, after 1 week of high-dose (1170 ± 88 mg/day) inpatient therapy; and after an 8-week intermediate (669 ± 129 mg/day) dosing phase. Serum levels of amiodarone and desethylamiodarone were measured by high-pressure liquid chromatography during follow-up electrophysiologic studies. Although the corrected sinus node recovery time, sinoatrial conduction time, and AH and HV intervals remained unchanged throughout the loading period, the sinus cycle length, Wenckebach cycle length, atrial and ventricular refractory periods, and ventricular tachycardia mean and return cycle lengths lengthened significantly by 1 week. They then remained stable for the remainder of the treatment period (control < 1 and 8 weeks, p < 0.05). In contrast, amiodarone and especially desethylamiodarone levels rose from 1 to 8 weeks: 1.29 ± 0.56 to 1.97 ± 0.90 μg/ml ( p = 0.001) and 0.63 ± 0.29 to 1.29 ± 0.61 μg/ml ( p < 0.0001), respectively. Because this regimen produces relatively prompt electrophysiologic changes, which then stabilize, early outpatient management becomes feasible before pharmacologic steady state is attained.

Electrophysiologic effects of intravenous verapamil in children after operations for congenital heart disease

To assess the effect of verapamil in children with congenital heart disease after surgical correction, an electrophysiologic study was undertaken in 19 patients, 0.8 to 15 years old. Atrial pacing and programmed atrial extrastimulation were performed before and 5 mn after intravenous administration of verapamil. A significant increase in conduction time and refractory periods was observed at the atrioventricular node level. Dual or accessory atrioventricular pathways, present in 14 cases, appear to have been suppressed in 9. The effect on the sinus node was of particular interest: The corrected sinus node recovery time was strongly prolonged by verapamil in 6 patients, 5 of whom had undergone surgery with extensive atrial reconstruction (Senning 2, anomalous pulmonary venous return 3) and 1 of whom had undergone correction of tetralogy of Fallot. Additional effects of verapamil were the disappearance of a sinus node entrance block in 8 patients and emergence of an ectopic pacemaker in 6. Although verapamil has electrophysiologic properties that should make it a useful drug in the treatment of reentry tachycardia, caution is indicated after extensive atrial surgery because sinus node depression may occur.

Chronotropic effect of hydralazine and its mechanism in symptomatic sinus bradycardia

The positive chronotropic effect of hydralazine was studied in 9 patients with symptomatic sinus bradycardia. Hydralazine was given in an intravenous dose of 0.15 mg/kg and heart rate, blood pressure, sinoatrial conduction time (Narula method) and corrected sinus node recovery time were measured. The effect of hydralazine was also studied after total autonomic nervous system blockade using 0.04 mg/kg of atropine and 0.2 mg/kg of propranolol intravenously. In the control state hydralazine produced an increase of 28 +/- 15% (mean +/- standard deviation) in heart rate, and this was essentially due to a decrease in sinoatrial conduction time (by 32 +/- 32%, p less than 0.05). Corrected sinus node recovery time also tended to shorten (decrease of 21 +/- 34%, difference not significant). After total autonomic blockade intrinsic heart rate did not change or increased very little (9 +/- 14%) after administration of hydralazine and there was no consistent change in sinoatrial conduction and corrected sinus node recovery times. The small residual effect of hydralazine on heart rate was related to incomplete autonomic blockade, since the effect of postural change (standing) on heart rate was also not totally abolished. The study showed that the positive chronotropic effect of hydralazine was mainly due to a change in sinoatrial conduction with a smaller change in corrected sinus node recovery time, and the major chronotropic effect of the drug was mediated by the autonomic nervous system.

Variations of normal sinus node function in relation to age: role of autonomic influence.

An electrophysiological study of sinus node function, including measurements of resting heart rate, maximal corrected sinus node recovery time and sinoatrial conduction time, was performed in 30 patients, 12-79 years of age, without any clinical, electrocardiographic or electrophysiological evidence of sinus node disease. To analyse autonomic influences, variables were measured before and after sympathetic and parasympathetic blockade. No significant correlations were observed between age and electrophysiological measurements of sinus node function at the control study or after sympathetic blockade. In contrast, the electrophysiological parameters of intrinsic sinus node activity were correlated with age and showed a progressive lengthening of mean sinus cycle length, of maximal corrected sinus node recovery time and of sinoatrial conduction time. In addition, measurements after vagolysis suggest a progressive decrease of parasympathetic activity with increasing age. These data also indicate that the respective role of the two components of the autonomic nervous system vary with increasing age: parasympathetic activity predominates in younger subjects; sympathetic and parasympathetic tones are equilibrated in older subjects. The normal sinus node function represents an equilibrated system: in parallel with ageing of the intrinsic properties of the sinus node, parasympathetic activity decreases so that basal properties remain stable throughout life.

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 < 0.001). The AH interval at an identical paced rate decreased from 119 ± 36 msec to 93 ± 17.6 msec after autonomic blockade ( P < 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.

Reproducibility of Electrophysiologic Parameters of Extrinsic Sinus Node Function in Patients with and without Sick Sinus Syndrome

In a group of 50 patients we investigated the daily reproducibility of the resting heart rate (RHR), the maximal corrected sinus node recovery time (CSNRTM), the pacing rate at which the CSNRTM occurred (OP), and the sinoatrial conduction time (SACT) during basal state. The study population was divided into two groups according to the presence or absence (as evidenced during the initial electrophysiologic study) of sinus node disease: group I included 35 patients with normal sinus node function, and group II included 15 patients with sick sinus syndrome. The electrophysiologic study was repeated approximately at the same hour and under similar conditions after an interval of at least two days (mean: 3.2 days for group I and 4.7 days for group II). The results showed good reproducibility with the exception of RHR in group I which slightly but significantly decreased in the second electrophysiologic study. The daily variations of the sinus node parameters appeared to be of similar levels in the two groups except for the CSNRTM; this parameter showed wide variations in single values in both groups, more marked in group II than in group I. Furthermore, if the CSNRTM and/or SACT were normal, it was likely that they would remain normal whatever the electrophysiologic status of the patient. Inversely, the change of status from abnormal to normal CSNRTM or SACT was not uncommon in patients with electrophysiologic signs of sinus node disease.

Effects of magnesium sulfate on cardiac conduction and refractoriness in humans

Magnesium has been used empirically for several decades in the treatment of atrial and ventricular arrhythmias in patients with normal and decreased serum magnesium levels. However, a systematic evaluation of the effects of magnesium on cardiac conduction and refractoriness in humans has not been described. In this study, the electrocardiographic and electrophysiologic effects of magnesium were determined in 10 patients with normal baseline serum magnesium and other electrolyte levels. Six grams of magnesium sulfate was administered intravenously over 6 minutes followed by a continuous infusion of 1 additional gram over 1 hour. Serum magnesium levels rose significantly from a baseline of 2.0 +/- 0.2 to 5.4 +/- 0.4 mg/dl (p less than 0.001). No significant change occurred in heart rate at rest, or in duration of the QRS complex or QT or QTc intervals during sinus rhythm. There were significant increases in sinus node recovery time (1,000 +/- 211 to 1,106 +/- 223 ms, p less than 0.01) and corrected sinus node recovery time (279 +/- 87 to 336 +/- 104 ms, p less than 0.05). Significant increases occurred in atrioventricular (AV) node conduction time during sinus rhythm (82 +/- 22 to 97 +/- 17 ms, p less than 0.02), in the atrial paced cycle length at which AV node Wenckebach block occurred (350 +/- 46 to 419 +/- 65 ms, p less than 0.01) and in the AV node relative refractory period (397 +/- 27 to 422 +/- 18 ms, p less than 0.05), functional refractory period (395 +/- 41 to 415 +/- 33 ms, p less than 0.05) and effective refractory period (306 +/- 67 to 338 +/- 38 ms, p less than 0.05).

Hemodynamic influences on sinus node recovery time: Effects of autonomic blockade

Ten patients with normal sinus node function were evaluated prospectively, to determine whether the decrease in blood pressure during rapid atrial pacing shortens the corrected sinus node recovery time. All patients had 30 seconds of atrial pacing at cycle lengths from 600 to 300 ms, with continuous arterial pressure monitoring, before and after intravenous administration of propranolol (0.2 mg/kg body weight) and atropine (0.04 mg/kg). In the control state, a decrease in corrected sinus node recovery time was recorded with faster atrial pacing rates, which was significantly related to the initial drop in systolic blood pressure at the onset of atrial pacing. Specifically, as the initial pressure drop increased from 15 mm Hg or less to 16 to 45 and 45 to 100 mm Hg, corrected sinus node recovery time decreased from 272 +/- 79 to 205 +/- 70 ms (p less than 0.04) and to 134 +/- 120 ms (p less than 0.04), respectively. In contrast, after autonomic blockade, the corrected sinus node recovery time was prolonged, in a near linear fashion, as atrial pacing rates increased. The magnitude of blood pressure drop with atrial pacing did not differ significantly from that in the control state at similar pacing rates. These findings suggest that hypotension during rapid atrial pacing activates autonomic reflexes that significantly shorten the corrected sinus node recovery time. Autonomic blockade negates this effect and the corrected sinus node recovery time prolongs with faster atrial pacing.

Inhibitory effect of acute and chronic administration of digitalis on the sick sinus node.

We have determined the effects of the acute administration of intravenous (i.v.) digitalis administration (0.8 mg of digoxin in 5-10 min) on the electrophysiological variables of 12 normal subjects (group 1), 12 patients with asymptomatic sinus node bradycardia (group 2) and 34 patients with symptomatic sinus node dysfunction (SSS) (group 3). The injection of digitalis induced: an increase of sinus node cycle length (SNCL) in all groups; a 10% increase of sinus node recovery time (SNRT) in group 1, no changes in group 2 and a 25% increase in group 3; a tendency to increase, without reaching statistical significance, of corrected sinus node recovery time (CSNRT) and sino-atrial conduction time (SACT) in all groups. In 16 patients of group 3 the effects of oral chronic treatment with digoxin (0.25 mg daily for 7 days) was also determined. The results show that chronic treatment did not further affect SNCL, SNRT or CSNRT, but caused a greater increase of SACT than did the acute i.v. administration. Chronic treatment significantly reduced the sinus rate and increased the number of premature supraventricular and ventricular beats, measured by means of 24 hour-Holter monitoring. These data suggest that digitalis should be used with great caution in patients with SSS.

Conduction abnormalities detected by electrophysiologic testing following repair of ostium primum atrioventricular septal defect

Since 1983 we have performed electrophysiologic studies in 6 patients who had previously undergone repair of an ostium primum atrioventricular septal defect. Information obtained during electrophysiologic studies was crucial in guiding appropriate pacemaker therapy in these patients. As judged from the resting electrocardiogram, sinus or junctional bradycardia was present in 3 6 , atrial flutter/fibrillation in 2 6 , and paced rhythm in 2 patients who had had ventricular pacemakers implanted for complete atrioventricular block. During maximal exercise testing 4 patients had reduced heart rates; 2 had sudden drops in heart rate at 1 min postexercise; 1 patient had exercise induced ventricular bigeminy; and 1 patient with atrial flutter and 2:1–4:1 block at rest developed 1:1 conduction during Stage II with an effective ventricular rate of 220/min. During electrophysiologic studies, the maximum corrected sinus node recovery time was abnormal in five of the six, ranging from 410 to 5630 msec. There was no spontaneous atrial rhythm in the other patient. Complete atrioventricular block was present in 2 patients while the atrioventricular Wenckebach phenomenon occurred abnormally at atrial pacing cycle lengths > 450 msec in 2 others. Supraventricular tachycardia or atrial flutter/fibrillation, was either spontaneous or induced in 2 6 patients, while ventricular tachycardia was induced in 1 3 patients who underwent programmed ventricular stimulation. Electrophysiologic studies were important in unmasking severe sinus node disease in 3 patients and atrioventricular node disease in 2. We therefore recommend that electrophysiologic studies be strongly considered as part of the evaluation of conduction abnormalities following repair of ostium primum atrioventricular septal defect.

Cardiac electrophysiologic actions of SCH 19927 (dilevalol), the R, R-isomer of labetalol

The cardiac electrophysiologic, hypotensive and antiadrenergic actions of SCH 19927, the R,R-isomer of labetalol, were evaluated in urethane-anesthetized dogs. The cumulative administration of 0.3, 1.0 and 3.0 mg/kg i.v. decreased mean arterial pressure by 18 to 26 mm Hg from a pretreatment value of 106 +/- 6 mm Hg and slightly enhanced atrioventricular nodal conduction. After 3.0 mg/kg of SCH 19927, sinoatrial (SA) conduction times were decreased, whereas intraventricular conduction was depressed slightly. SCH 19927, 10.0 mg/kg, reduced mean arterial pressure by 39 mm Hg and enhanced SA nodal conduction and recovery after overdrive pacing (decreased SA conduction time and corrected sinus node recovery times), whereas intraventricular conduction times and the rate-corrected QTc interval were prolonged. Sinus heart rate, atrial, ventricular and atrioventricular nodal functional and effective refractory periods were unaltered by SCH 19927, 0.3 to 10.0 mg/kg. The administration of SCH 19927 produced significant beta adrenergic receptor blockade, as determined by inhibition of the positive chronotropic and peripheral vasodilatory response to isoproterenol, but did not alter the alpha-1 adrenergic receptor-mediated vasopressor response to phenylephrine. The results indicate that SCH 19927, in beta adrenergic receptor blocking and hypotensive dosages, does not depress SA nodal or atrioventricular nodal function, thus suggesting an electrophysiologic spectrum of activity different from that of other beta adrenergic receptor antagonists.

Clinical electrophysiology of flestolol, a potent ultra short-acting beta blocker

We measured the electrophysiologic effects of flestolol, and ultra short-acting beta blocker, in 15 patients at two infusion rates: a 45 μg/kg loading dose followed by a 5 μg/kg/min infusion and a 60 μg/kg loading dose followed by a 10 μg/kg/min infusion. Electrophysiologic measurements were made after 15 minutes at each infusion rate (plasma concentrations 46 ± 11 and 94 ± 23 ng/ml). Flestolol produced dose-dependent effects on the sinus node, the atrioventricular (AV) node, and right ventricular refractoriness, whereas atrial refractoriness and infranodal conduction were unchanged. At the 10 μg/kg/min dose, flestolol prolonged sinus cycle length by a mean of 20% ( p = 0.0001), corrected sinus node recovery time by 42% ( p = 0.02), AH interval by 21% ( p = 0.0001), AV node effective refractory period by 28%, AV node Wenckebach cycle length by 30% (0.0001), and right ventricular effective refractory period by 5% ( p = 0.03). A significant concentration-effect relationship ( p ≤ 0.03) was present for all variables which had significant dose-effect relationships. No patient developed hypotension, bradyarrhythmias, or other toxicity. Sinus cycle length decreased linearly with time in the post infusion period ( r = 0.99); by 30 minutes post infusion, measured electrophysiologic variables had returned to control values and flestolol plasma concentration had decreased to 4 ± 2 ng/ml. Flestolol's electrophysiologic effects are similar to those of other beta blockers. In doses up to 10 μg/kg/min, it is safe in selected patients, has rapid onset and offset of action, and does not cause acute rebound.

Electrophysiological effects of diphenylhydantoin in patients with sinus node dysfunction.

The electrophysiological effects of intravenous administration of diphenylhydantoin (DPH) (5 mg/Kg, maximum 250 mg) were studied in 20 patients with sinus node dysfunction (SND). DPH shortened spontaneous cycle length (SCL) in 3 patients and lengthened it in 3. Maximum corrected sinus node recovery time (max CSRT) was prolonged in 7 patients and shortened in 3. Estimated sinoatrial conduction time was prolonged in 3 patients and shortened in 2 of 10 patients in whom this measurement was possible. However, these changes were not statistically significant. Neither were there any significant changes in PA, AH and HV intervals nor refractory periods of the atrium, the AV node and the ventricle. DPH prolonged SCL and/or max CSRT in 9 of 20 patients with SND, and it was suggested that DPH has depressant effects on the sinus node in some patients with SND. Thus, this drug should be used with caution in the treatment of ventricular arrhythmias accompanied by sinus node dysfunction.

Study of the Electrophysiologic Properties of Clonidine Administered Intravenously

A few cases of sinus node dysfunction (SND) and AV block (AVB) were described with clonidine therapy. The aim of this study is to evaluate the electrophysiologic properties of clonidine in volunteers with normal electrophysiologic data. Twenty-eight subjects were investigated by endocavitary techniques. The following parameters were measured before and 20 min after intravenous administration of clonidine: systolic and diastolic blood pressure (BP); sinus cycle (SC); PA, AH, and HV intervals; effective (ERP) and functional (FRP) refractory period of right atria (RA); AV node (AVN); His Purkinje system (HP); right ventricle (RV); corrected sinus node recovery time (SNRT); and sinoatrial conduction time (SACT). Blood pressure was reduced from 149/89 to 115/74 mm Hg. Sinus cycle was prolonged by 71 ms (p less than 0.01), corrected SNRT by 81 ms (p less than 0.05), and FRP of AVN by 16 ms (p less than 0.05). SND was more marked when initial SC was longer. Atrioventricular node depression was more marked when the PR interval was longer and when subject was older. Electrophysiologic effects of clonidine are similar to those of beta-blockers. The tensional effects are more marked than electrophysiologic effects. Clonidine in the high risk subject (age, bradycardia, long PR) may be cautiously dosed. Drug association with digitalis antiarrhythmic drugs, beta-blockers, and calcium antagonists may be avoided.

Effects of Cimetidine on Sinus Node Function and Atrioventricular Conduction in Man

Electrophysiological effects of H2‐receptor blockade 200 mg cimetidine IV on sinus node (SN) function and atrioventricular (AV) conduction were evaluated. Tests were performed in 21 people in basal state (group I), and in 14 people (group II) after autonomic blockade (AB) (propranolol 0.2 mg/kg, and atropine 0.04 mg/kg). We analyzed sinus cycle length (SCL), sinus node recovery time (SNRT), corrected sinus node recovery time (CSNRT), and secondary pause (SP) as the longest sinus pause after incremental overdrive pacing, sinoatrial conduction time (Strauss method) (SACT), Wenckebach point (WP), and blood pressure (BP). In group I, cimetidine prolonged SCL (717 ± 98 vs 860 ± 138 msec P &lt; 0.001), SNRT (1161 ± 153 vs 1263 ± 163 msec P &lt; 0.002), SP (943 ± 183 vs 1072 ± 187 msec P &lt; 0.001), SACT (121 ± 20 msec vs 149 ± 21 msec P &lt; 0.002), and lowered rate at which AV nodal Wenckebach point were observed (169 ± 24 vs 160 ± 26 beats/min P &lt; 0.02). The drug did not produce significant change of the CSNRT (439 ± 121 vs 402 ± 107 msec. In group II, after AB cimetidine prolonged SCL (643 ± 79 vs 656 ± 86 msec P &lt; 0.05), SP (686 ± 114 vs 717 ± 109 msec P &lt; 0.05) and lowered WP (170 ± 19 vs 166 ± 19 beats/min P &lt; 0.02) significantly. The effects of cimetidine, after AB on SNRT (894 ± 180 vs 920 ± 164 msec, CSNRT (243 ± 99 vs 255 ± 85 msec), SACT (85 ± 20 msec vs 90 ± 22 msec) were not significant. We conclude that H2‐receptor blockade decreases SN automatically, prolongs SACT and AV conduction in man. The study suggests that histamine takes part in regulation of electrophysiological properties of the human heart in vivo.