Differential effects of functional autonomic blockade on the variables of sinus nodal automaticity in sick sinus syndrome

To study the pathophysiologic mechanism of sick sinus syndrome and to establish the relation of intrinsic heart rate, corrected sinus nodal recovery time and sinoatrial conduction time in this syndrome, electrophysiologic studies were conducted in 22 men (mean age 60 ± 12 years) with the clinical diagnosis of sick sinus syndrome. Measurements were determined before and after autonomic blockade with propranolol (0.2 mg/kg body weight) and atropine sulfate (0.04 mg/kg). Fifty-nine percent of patients (Group I) had an abnormal intrinsic heart rate, suggesting intrinsic abnormality of sinus nodal automaticity; 41 percent (Group II) had a normal intrinsic heart rate after autonomic blockade, suggesting disturbed autonomic regulation. One patient with an observed intrinsic heart rate higher than the upper limit of predicted intrinsic heart rate was also included in Group II. The mean corrected sinus nodal recovery time before autonomic blockade was 751 ± 502.8 ms and was abnormal (more than 450 ms) in 10 of the 13 patients in Group I and 2 of the 9 patients in Group II. After autonomic blockade this interval was 694 ± 638.7 ms and was abnormal in 12 of the 13 patients in Group I and in 2 of the 9 patients in Group II. The patients in each group could be further classified into three groups on the basis of normal or abnormal corrected sinus nodal recovery time before or after autonomic blockade. Not all patients with abnormal intrinsic heart rate (Group I) had abnormal corrected sinus nodal recovery time and vice versa. Patients in Group II were younger in age, had a lesser incidence of organic heart disease and were more severely symptomatic.Mean sinoatrial conduction time during control studies was 210.4 ±96.3 ms and decreased significantly (143.2 ± 59.6 ms, p < 0.005) after autonomic blockade. This interval was abnormal in 3 of the 13 patients in Group I and in 6 of the 9 patients in Group II during control studies; after autonomic blockade it remained abnormal in 3 patients in Group I and in 1 patient in Group II.It is concluded that determination of heart rate and corrected sinus nodal recovery time after autonomic blockade increases the sensitivity of electrophysiologic testing and offers some insight into the pathophysiology of sick sinus syndrome. Patients with sick sinus syndrome who have a normal intrinsic heart rate have a greater incidence of abnormal sinoatrial conduction time than do those with an abnormal intrinsic heart rate. Thus, abnormal sinoatrial conduction time is usually due to extrinsic autonomic influences.     

Electrophysiologic effect of digitalis on sinoatrial nodal function in children

Despite the prevalence of digitalis usage in children, the electrophysiologic effects of digitalis on sinoatrial (S-A) nodal function is unknown in this age group. The purpose of this study was to determine the effect of digitalis on sinoatrial conduction time as well as on S-A nodal automaticity. Ten subjects (mean age 10.5 years) underwent electrophysiologic assessment of S-A nodal function before and 30 minutes after administration of ouabain (0.01 mg/kg). Total S-A conduction time increased in each subject and the mean value after ouabain (182 msec ± 13 standard errors of the mean [SEM]) was significantly higher (P < 0.01) than before (149 msec ± 11). The sinus cycle length was variable after ouabain (P > 0.1). The corrected sinus nodal recovery time also was variable (P > 0.1), decreasing substantially in three subjects. Mechanisms of the effect of digitalis on the S-A node and atrium are proposed and discussed.

It is concluded that digitalis prolongs the S-A conduction time in children with normal S-A nodal function. By prolonging the S-A conduction time, digitalis may artifactually shorten corrected S-A nodal recovery time in some patients.     

Effects of digoxin on sinus nodal function before and after vagal blockade in patients with sinus nodal dysfunction: a clue to the mechanisms of the action of digitalis on the sinus node.

To increase the limited knowledge of the effects of digitalis on sinus nodal function in patients with sinus nodal dysfunction and to initiate an investigation into the mechanisms underlying its effects, 34 patients with sinus nodal dysfunction were studied. Twenty patients underwent determination of sinus cycle length, estimated sinoatrial conduction time and maximal corrected sinus recovery time before and after the administration of 0.75 mg of intravenous digoxin. For the group, sinus cycle length did not change, sinoatrial conduction time increased insignificantly and maximal corrected sinus recovery time shortened; however, individual variation occurred. The effects of acute digitalization appeared to predict the effects of chronic digitalis administration on sinus nodal function in the eight patients who subsequently continued to take digoxin. Fourteen patients received digoxin after vagal blockade with atropine. After vagal blockade, digoxin lengthened sinus cycle length, sinoatrial conduction time and maximal corrected sinus recovery time. The effects of digoxin administered after atropine could be antiadrenergic, direct, or both, and are opposite to those induced by atropine alone. Because these effects are similar to those of vagotonia yet are not apparent when the vagi are unblocked, digoxin may have direct excitatory, adrenergic or previously unrecognized vagolytic effects on sinus nodal function in man and their manifestation may be dependent on heart rate or autonomic tone.     

Electrophysiologic effects of flecainide acetate in patients with sinus nodal dysfunction

Flecainide acetate (R818) is a new antiarrhythmic agent for oral and intravenous use; it has predominantly class I properties and a long plasma half-life. Electrophysiologic effects were evaluated in 11 patients with sinus nodal dysfunction before administration of flecainide acetate and 15 to 60 minutes after intravenous administration of 1.5 mg/kg body weight of flecainide acetate given over 15 minutes. In 8 of 11 patients the maximal sinus nodal recovery time increased after flecainide acetate. However, the mean maximal sinus nodal recovery time was not statistically significantly increased from 1,929 ± 184 (mean ± standard error of the mean [SEM]) to 2,770 ± 500 ms (p <0.10). The corrected sinus nodal recovery time increased from 875 ± 181 before to 1,727 ± 507 ms after administration of flecainide acetate (p <0.05). The sinus cycle length and sinoatrial conduction time were not significantly changed. Flecainide acetate induced a marked prolongation of the H-V interval (from 41 ± 3 to 52 ± 4 ms [p <0.01]) as well as a significant increase in the A-H interval, QRS duration, and QT₁₀₀ interval. The effective and functional refractory periods of the atria increased by 12% (p <0.01) and 11% (p <0.01), respectively. The atrioventricular (AV) nodal functional refractory period increased significantly by 7% (p <0.01), whereas the 9% prolongation of the effective refractory period was not statistically significant. No side effects were observed. It is concluded that flecainide acetate prolongs atrial and ventricular conduction and refractoriness, and thus appears to be a potent antiarrhythmic agent. However, the sinus nodal function is depressed, and thus caution is advised in the use of flecainide acetate in patients with sinus nodal dysfunction.     

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.     

Electrophysiologic evaluation of sinus node dysfunction in postoperative children and young adults utilizing combined autonomic blockade

Sinus node dysfunction is a recognized problem following surgery for congenital heart disease. Seven postoperative patients with sinus node dysfunction (5 Mustard, 1 tetralogy of Fallot, 1 Fontan) underwent electrophysiology study of sinus node function during combined autonomic blockade (CAB) utilizing propranolol 0.2 mg/kg i.v. and atropine 0.04 mg/kg i.v. to evaluate intrinsic sinus node function isolated from autonomic control. During CAB, intrinsic heart rate, intrinsic corrected sinus node recovery time, and intrinsic sinoatrial recovery time were measured. These results were compared with age-matched normal intrinsic data from our lab [normal (n = 7, mean age 9 years) IHR 128 +/- 24, intrinsic corrected sinus node recovery time 135 +/- 40 ms, intrinsic sinoatrial conduction time 86 +/- 19 ms]. Among postoperative Mustard patients (n = 5, mean age 13 years, mean years postoperative 11) 2 of 5 had clearly abnormal intrinsic sinus node function with nonsinus rhythm during CAB; 3 of 5 had sinus rhythm during CAB with normal or mildly abnormal intrinsic sinus node function. The postoperative case of tetralogy of Fallot (age 20 years, postoperative 14 years) had mildly abnormal intrinsic sinus node electrophysiology study. The postoperative case of Fontan (age 16 years, postoperative 1.5 years) had sinus rhythm at rest but left atrial rhythm during CAB. Different aspects of sinus node dysfunction may be expressed during resting electrophysiology study vs. electrophysiology study utilizing CAB. The pathophysiology of sinus node dysfunction among postoperative pediatric patients is not homogeneous with regard to the contribution of intrinsic sinus node dysfunction. In those patients with normal or mildly abnormal intrinsic sinus node function, an important pathophysiologic influence of the autonomic nervous system is implicated.     

Cardiac autonomic blockade in sinus disease and indication for a pacemaker

Functional autonomic blockade (FAB) with metoprolol (0.2 mg/kg body weight) and atropine sulphate (0.04 mg/kg) was carried out in 23 patients, 20 to 81 years old (mean age 61 years) with symptomatic sick sinus syndrome with clinical indication for permanent pacing. Several measurements were determined before and after FAB, 7 had normal intrinsic heart rate (IHR) and 16 abnormal. With normal IHR, 3 had severe autonomic regulation disturbances and in only two patients the corrected sinus nodal recovery time (SNRTC) and the sinoatrial conduction time (SACT) were prolonged after FAB. On the 16 patients with abnormal IHR only 4 had severe extrinsic autonomic influence and 15 had SACT and SNRTC prolonged after FAB. All measurements were determined by standard electrocardiographic surface tracings. Indications for permanent pacing were reduced to intrinsic sick sinus syndrome and bradycardia with severe autonomic disturbances in symptomatic patients.     

Reproducibility of electrophysiological parameters of sinus node following autonomic blockade

We investigated the reproducibility of sinus node cycle length (SCL), corrected sinus node recovery time (CSRT) and sino-atrial conduction time (SACT) during the control state and following autonomic blockade in 25 patients (mean age: 56.9 ± 13.8 years). Autonomic blockade was induced by i.v. administration of propranolol (0.2 mg/kg) and atropine (0.04 mg/kg). The electrophysiological study was repeated after 24 hr and the results were compared. The patients were divided into two groups: Group 1 (15) with normal and Group 2 (10) with abnormal intrinsic sinus node function. Following autonomic blockade in Group 1 the daily variations in SCL, CSRT and SACT were very slight whereas in Group 2 there was far greater variability in these parameters. However, in the latter group there were no patients who changed their status from prolonged to normal intrinsic CSRT on the second study, whereas SACT changed its status in 2 patients. In Group 1 the daily variations in sinus node parameters were much slighter following autonomic blockade than during the control state. In Group 2 the variations were very similar during control and following autonomic blockade.These data suggest that: (1) following autonomic blockade the reproducibility of sinus node parameters is very good in Group 1, whereas in Group 2 several patients show marked daily variations in sinus node parameters; (2) following autonomic blockade the sinus node electrophysiological parameters are meaningful in diagnosing an involvement of intrinsic sinus node function; and (3) in patients with abnormal sinus node parameters during control state, but with normal intrinsic sinus node function, the daily variations are mainly due to change in autonomic tone, whereas when the intrinsic sinus node function is abnormal, the day to day variations during control state appear due predominantly to intrinsic sinus node abnormalities.     

Effects of propafenone on sinus nodal and ventricular automaticity: in vitro and in vivo correlation

The electrophysiologic effects of the new antiarrhythmic drug, propafenone, were evaluated in anesthetized closed-chest dogs and on isolated cardiac tissues with the microelectrode technique. Propafenone (2 to 4 mg/kg intravenously) had no effect on sinus rate or on sinus nodal recovery time, but caused a dose-dependent significant decrease in the rate of idioventricular rhythm and increased the duration of ventricular overdrive suppression in dogs (n = 8) with complete atrioventricular block. On isolated canine Purkinje fibers (n = 8) manifesting automaticity with resting membrane potential less negative than -70 mV, propafenone reduced the slope of phase 4 depolarization and reduced the rate of automatic impulse initiation in a concentration-dependent manner (10(-6) M-4.10(-5) M). At these concentrations, propafenone had no effect on rabbit sinus nodal automaticity (n = 8) or on sinoatrial conduction. However, significant depression of sinus nodal automaticity occurred with propafenone concentrations above 5.10(-6) M in the presence of cholinergic or complete autonomic blockade with atropine (10(-6) M) and propranolol (5.10(-5) M). Propafenone caused a concentration-dependent decrease in the disparity of Purkinje fiber-ventricular muscle action potential duration (APD), mainly by shortening Purkinje fiber APD. We conclude: that propafenone suppresses idioventricular rhythm in the intact dog, most likely by depressing Purkinje fiber automaticity; the depressant effect of propafenone on sinus nodal automaticity is evident only during cholinergic receptor blockade; and the antiarrhythmic properties of propafenone may include removal of APD disparity by selective shortening of Purkinje fiber and not of ventricular muscle APD.     

Electrophysiologic effects of oral diltiazem before and after beta blockade

We conducted electrophysiologic (EP) studies and estimated the sinus node function and atrioventricular (AV) conduction in 10 patients with suspected coronary arterial disease (age range 35-55 years) before and during diltiazem therapy (60 mg thrice daily for 5-7 days). The effect of beta blockade (0.1 mg/kg of intravenous propranolol) was evaluated in both EP studies. The mean spontaneous sinus cycle length (SCL) and the AV nodal Wenckebach cycle lengths (AVWB) were significantly higher (p less than 0.05) after propranolol alone (913 +/- 131 and 504 +/- 197 ms, respectively) compared with baseline values (SCL: 827 +/- 149 ms, AVWB: 439 +/- 173 ms). Diltiazem alone failed to influence the SCL and AVWB significantly. Following the combination (diltiazem + propranolol), SCL (945 +/- 147 ms) and AVWB (533 +/- 148 ms) were significantly higher (p less than 0.05) than baseline and post diltiazem values (SCL: 840 +/- 150 ms; AVWB 457 +/- 103 ms). None of the other parameters (sinoatrial conduction time, corrected sinus node recovery time, AH and HV intervals, AV nodal and atrial effective refractory periods) were significantly influenced by propranolol, diltiazem, or the combination. No patient developed AV block, sinus arrest/sinoatrial exit block, or symptomatic sinus bradycardia following beta blockade after diltiazem administration. Oral diltiazem therapy alone and after beta blockade does not appear to adversely influence the sinus node function and AV conduction in patients below the age of 55 years. The combination of diltiazem and beta blocker thus appears safe in selected patients with coronary arterial disease.     

Autonomic blockade and sick sinus syndrome. New concept in the interpretation of electrophysiological and Holter data

Autonomic blockade is commonly employed as a test of sinus nodedysfunction. We compared primary and secondary atrial postpacingpauses and postextrasystolic sino-atrial responses before andafter autonomic blockade in 56 patients with the clinical diagnosisof sick sinus syndrome. Pharmacological autonomic blockade wasachieved by atropine 0.04 mg kg^–1 and propranolol 0.2mg kg^–1 i.v. In a group of patients with a normal intrinsicheart rate the number of positive electrophysiologic variablesassociated with sinus node dysfunction declined after autonomicblockade. In 91% of these patients, sinus node function wascharacterized by a normal intrinsic recovery time, gradual exponentialreturn to the constant sinus cycle length, and biphasic postextrasystolicreturn responses. Three patients in this group had intrinsicSA-block revealed by atrial pacing and verified by Holter monitoring.Besides normal intrinsic pacemaker properties in 53% of patients,rhythm monitoring revealed severe sinus node dysfunction asmanifested by bradycardia and the tachycardia-bradycardia syndrome.SA-block and sinus arrest up to 29120 ms. In the abnormal intrinsicheart rate group, disturbed intrinsic rhythmicity was characterizedin all by a prolonged corrected intrinsic recovery time (2320±2740ms [± SD]), arrhythmia and/or brady-cardia in the secondarypostpacing cycles, chaotic postextrasystolic patterns, or prolongedsinoatrial conduction times. Significantly slow minimal heartrates during sleep significantly prolonged average sinus cyclelengths and positive ECGs for sinoatrial disorders in the wakingperiod were present on the 24-rhythm recording. It is concluded that intrinsic heart rate obtained by autonomicblockade is the best and most simple method for the diagnosisof intrinsic sinus node dysfunction. Combined autonomic blockadeand electro-physiological tests can be of great value in unmaskingthe severity and degree of intrinsic dysfunction and analyzingthe abnormality of secondary pacemaker function. These investigations,however, are rather insensitive and therefore ineffective indetecting autonomic sinus node dysfunction. To assess the roleand significance of the autonomous neurovegetative tone in thegenesis of sinoatrial disorders, rhythm monitoring is required.     

Electrophysiologic effects of flecainide acetate on sinus node function, anomalous atrioventricular connections, and pacemaker thresholds

The acute electrophysiologic effects of i.v. flecainide acetate (2 mg/kg body weight) were assessed in 71 patients undergoing electrophysiologic study. Ten patients underwent investigation for sinus node dysfunction. Sinus cycle length shortened slightly, from 980 +/- 292 to 931 +/- 276 ms (p less than 0.01). Uncorrected or corrected sinus node recovery times or sinoatrial conduction time (according to the methods of Strauss and Narula) did not change in 6 patients with normal sinus node function and in 3 of 4 patients with abnormal sinus node function at rest. In the remaining patient maximal sinus node recovery time increased from a value at rest of 5,185 ms to 23,460 ms after flecainide. In the same patient sinoatrial conduction times at rest increased from 159 ms (Strauss method) and 143 ms (Narula method) to 1,398 and 1,455 ms, respectively, after flecainide. Thirty-three patients underwent electrophysiologic evaluation of anomalous atrioventricular (AV) pathways and reentrant tachycardias. Flecainide significantly prolonged accessory AV pathway anterograde and retrograde refractoriness. Anterograde accessory pathway block occurred in 33% of patients and retrograde accessory pathway block in 44%. Flecainide was successful in the acute termination of 86% of orthodromic atrioventricular reentrant tachycardias. In 15 patients with dual AV nodal pathways, only retrograde "fast" AH pathway refractoriness was significantly increased by flecainide, which was successful in the acute termination of 88% of intra-AV nodal reentrant tachycardias. In 28 patients who underwent endocardial pacing threshold assessment before and after i.v. flecainide, the acute threshold rose by a maximum of 117%, whereas the chronic threshold rose by a maximum of 83%.(ABSTRACT TRUNCATED AT 250 WORDS)     

The role of the autonomic nervous system on sinus node function in patients with intermittent sinoatrial block

Sinus node (SN) function was analyzed with and without autonomic blockade (AB) in 31 patients (mean age: 57.6 +/- 12.8) with intermittent sinoatrial block. Twenty-one patients had organic heart disease; in the remaining ten signs of underlying heart disease were not present. Nineteen patients had dizziness or syncope. Sinus cycle length, sinus rate, corrected sinus node recovery time (CSRT) and sinoatrial conduction time (SACT) were analyzed. After control measurements, AB was produced by i.v. propranolol (0.2 mg/Kg) and atropine (0.04 mg/Kg). Measurements of electrophysiological parameters were then repeated. After AB sinus rate and CSRT did not show statistically significant differences, whereas SACT decreased significantly (P less than 0.001). When intrinsic heart rate (IHR) was abnormal (11 cases), intrinsic CSRT was always abnormal, whereas when IHR was normal, intrinsic CSRT was normal in 11 patients and abnormal in nine. In several cases, when sinus rate increased after AB, CSRT decreased and vice-versa. The parameters of intrinsic SN function were normal in 80% of patients with a normal heart and only in 14.2% of patients with organic heart disease. These data indicate that: (1) during the control period SACT is mainly conditioned by the vagal tone; (2) abnormalities in control CSRT are not uniformly abolished after AB in patients with normal IHR; (3) AB has a differential effect on the two variables of SN automaticity; i.e. sinus rate and CSRT; and (4) in patients without underlying heart disease, the SN dysfunction is almost exclusively related to alterations of the autonomic nervous system.     

Chronotropic effect of hydralazine and its mechanism of 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.     

Assessment by autonomic blockade of age-related changes of the sinus node function and autonomic regulation in sick sinus syndrome

Age-related changes of the sinus node (SN) function and the autonomic influence on the SN function were evaluated in 65 patients with sick sinus syndrome (range 14 to 84 years). Heart rate (HR), corrected SN recovery time and sinoatrial conduction time were measured before (basic) and after (intrinsic) autonomic blockade (propranolol 0.2 mg/kg plus atropine 0.04 mg/kg intravenously). Percent of autonomic chronotropies of the SN function were calculated by the following formulas: (1)--(intrinsic HR--basic HR/intrinsic HR) X 100; (2) (intrinsic corrected SN recovery time--basic corrected SN recovery time/intrinsic corrected SN recovery time) X 100; (3) (intrinsic sinoatrial conduction time--basic sinoatrial conduction time/intrinsic sinoatrial conduction time) X 100. Basic HR, basic corrected SN recovery time and basic sinoatrial conduction time did not vary with age. Intrinsic HR decreased with age, but this correlation was weak (r = -0.54, p less than 0.001). Intrinsic corrected SN recovery time and intrinsic sinoatrial conduction time tended to increase with age (r = 0.26, p less than 0.05; r = 0.29, p less than 0.05, respectively). Percent chronotropies of HR, corrected SN recovery time and sinoatrial conduction time were negative values in younger patients and positive values in elderly patients; they correlated positively with age (r = 0.59, p less than 0.001; r = 0.60, p less than 0.001; r = 0.43, p less than 0.001, respectively). Thus, the basic SN function did not change with age, while the intrinsic SN function deteriorated with age.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evidence that cocaine slows cardiac conduction by an action on both AV nodal and His-Purkinje tissue in the dog

The effects of intravenous cocaine (2 mg/kg) were tested on several indices of cardiac electrical activity in sedated dogs. These included sinus rate, PR, AH, and HV intervals; AV nodal effective refractory period (AVNERP); ventricular effective refractory period; QRS duration; and the QT interval. Cocaine induced significant changes in six control animals with an intact-functioning autonomic nervous systems. After pharmacologic autonomic blockade with propranolol plus propantheline, cocaine increased the PR interval (+ 11 +/- 4.0 ms, p less than 0.05), primarily by slowing conduction at the AV nodal level. However, with constant atrial pacing at a rate above the sinus cycle length, prolongation of both the AH and the HV intervals (+ 15 +/- 2.5 and 6.7 +/- 1.7 ms, respectively) occurred. There was also a significant increase in the AVNERP (+ 29 +/- 5.9 ms, p less than 0.05). Consistent with the observed rate-dependent HV prolongation, cocaine decreased the rate of rise of phase 0 of the transmembrane action potential of Purkinje fibers. These data indicate that cocaine impairs cardiac conduction by direct actions on AV nodal and His-Purkinje cells.     

Electrophysiological effects and mechanism of action of oral quinidine in patients with sinus bradycardia and first degree A-V nodal block

The effects of quinidine on sinus nodal and A–V nodalfunction were assessed in 20 patients (age: 60±7 years)with sinus bradycardia and a prolonged A–H interval. Electrophysiologicalstudies were performed twice in each patient. In the first study,the measurements of sinus and A–V node function were evaluatedboth in the basal state and after autonomic blockade (propranolol0.2 mg kg^-1 and atropine 0.04 mg kg^-1). Oral quinidine was administeredfor 3–4 days (1200 mg day^-1) and the study was then repeatedusing the same methods. Comparison of data obtained in the twostudies in the basal state allowed us to evaluate the overalleffect of quinidine. Comparing the results obtained followingautonomic blockade, the direct action of the drug could be assessed.Inthe basal state quinidine did not significantly change the functionof either node. In contrast, after autonomic blockade, significantchanges were noted after quinidine. In 3 patients with sinusrate <50 beats min^-1 and an abnormal intrinsic heart rate,quinidine induced marked depression of sinus automaticity.Thesedata suggest that: (1) in patients with sinus bradycardia andprolongation of the A–H interval, oral quinidine has adirect depressant effect on sinus and A–V nodal function,but this effect is counteracted by autonomically mediated actions;(2) in patients with moderate or severe bradycardia and an abnormalintrinsic heart rate, the drug can induce marked depressionof sinus automaticity.     

Electrophysiological effects and mechanism of action of oral quinidine in patients with sinus bradycardia and first degree A-V nodal block

The effects of quinidine on sinus nodal and A–V nodalfunction were assessed in 20 patients (age: 60±7 years)with sinus bradycardia and a prolonged A–H interval. Electrophysiologicalstudies were performed twice in each patient. In the first study,the measurements of sinus and A–V node function were evaluatedboth in the basal state and after autonomic blockade (propranolol0.2 mg kg^-1 and atropine 0.04 mg kg^-1). Oral quinidine was administeredfor 3–4 days (1200 mg day^-1) and the study was then repeatedusing the same methods. Comparison of data obtained in the twostudies in the basal state allowed us to evaluate the overalleffect of quinidine. Comparing the results obtained followingautonomic blockade, the direct action of the drug could be assessed.Inthe basal state quinidine did not significantly change the functionof either node. In contrast, after autonomic blockade, significantchanges were noted after quinidine. In 3 patients with sinusrate <50 beats min^-1 and an abnormal intrinsic heart rate,quinidine induced marked depression of sinus automaticity.Thesedata suggest that: (1) in patients with sinus bradycardia andprolongation of the A–H interval, oral quinidine has adirect depressant effect on sinus and A–V nodal function,but this effect is counteracted by autonomically mediated actions;(2) in patients with moderate or severe bradycardia and an abnormalintrinsic heart rate, the drug can induce marked depressionof sinus automaticity.     

Method for recording electrical activity of the sinoatrial node and automatic atrial foci during cardiac catheterization in human subjects

A method for recording electrical activity of the sinoatrial (S-A) node and automatic atrial foci in human subjects is described. To record S-A nodal electrograms, an electrode catheter was inserted percutaneously into the femoral vein and advanced under fluoroscopic control to the superior vena caval-right atrial junction. The distal terminal of the catheter was placed in the area of the S-A node and the proximal terminal on the free right atrial wall or in the right atrial lumen. Polarity was reversed from the conventional electrocardiographic recording; high amplification (about 100 μV/cm) and selective filters (0.1 to 20 hertz) were used.S-A nodal electrograms recorded with this method in human subjects were similar to electrograms obtained previously from the dog and rabbit and revealed negatively directed diastolic and upstroke slopes preceding the P wave of the electrocardiogram. Sinoatrial conduction time measured from the S-A nodal electrograms in 15 cases was 34.9 ± 2.1 ms (mean ± standard error of the mean) for a sinus cycle length of 736.4 ± 38.6 ms. The coronary sinus electrograms in a patient with coronary sinus rhythm were recorded by the same technique except that the distal terminal of the catheter was placed at the coronary sinus ostium. A negatively directed diastolic slope preceding the P wave was consistently recorded.This method for recording electrograms of the S-A node and ectopic automatic atrial foci should prove useful in (1) assessment of both normal and abnormal S-A nodal function, (2) direct determination of conduction time from the S-A nodal pacemaker to the atrium, and (3) localization of automatic atrial foci.     

Intrinsic function of the sinus node in patients with syncope and positive vagal maneuvers

This study was undertaken to establish the nature (intrinsic or extrinsic) of sinus node dysfunction in patients presenting with syncope and abnormal response (sinus pause greater than 3') to vagal manoeuvres (carotid sinus massage and/or eye-ball compression). To this purpose 29 patients (20 males, 9 females, aged 18-79 yrs, mean = 60) underwent an electrophysiologic study. In all we measured before and after autonomic blockade with Propranolol (0.2 mg/kg) and Atropine sulfate (0.04 mg/kg) the following parameters: sinus rate, corrected sinus node recovery time and sino-atrial conduction time. According to the presence or absence of electrocardiographic signs of sinus node dysfunction the patients were divided into three groups: Group A: 11 patients without electrocardiographic signs of sinus node dysfunction; Group B: 13 patients with borderline electrocardiographic signs of sinus node dysfunction (sinus bradycardia between 40 and 60 beats/min); Group C: 5 patients with definite electrocardiographic signs of sinus node dysfunction (sinus bradycardia less than or equal to 39 beats/min and/or sinoatrial block and/or sinus arrest). Fifteen patients (52%) had signs of organic heart disease. The main results obtained were: At least one electrophysiological test (sinus rate, corrected sinus node recovery time or sino-atrial conduction time) was abnormal in 10 patients (34,5%) before autonomic blockade and in 8 patients (27%) after autonomic blockade. Two of these 8 patients belonged to Group A (18%), 1 to Group B (8%) and 5 to Group C (100%). Six of these 8 patients were suffering from an organic heart disease and 2 were not.(ABSTRACT TRUNCATED AT 250 WORDS)