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.     

Role of the autonomic nervous system in the genesis of first and second degree atrio-ventricular nodal block

Thirty-four patients with a prolonged A-H interval (group I)and 26 with A-V nodal Wenckebach block (group II) were studiedin the basal state and after autonomic blockade (propranolol0.2mg kg^–1 and atropine 0.04 mg kg^–1 in order toassess the role of autonomic system in A-V nodal conductiondisturbances. In group I, the A-H intervals did not change significantlyafter autonomic blockade, whereas pacing cycle length for Wenckebachblock, effective and functional refractory periods of the A-Vnode decreased significantly (P<005). In the 22 patientswith organic heart disease these variables did not change significantlyafter autonomic blockade, whereas in the 12 without underlyingheart disease, they decreased in all cases (P< 0001). Inthe former, the variables of intrinsic A-V nodal conductionwere normal in only 6% of patients, whereas in the latter theywere normal in 66%. Also in group II, the intrinsic A-H intervalswere normal in only 6% of patients with cardiac disease butwere normal in 63% without underlying heart disease. These datasuggest that in the patients with first and second degree A-Vnodal block and organic heart disease, the conduction disturbanceis predominantly related to intrinsic involvement of A-V node,whereas in the subjects without underlying heart disease theA-V nodal blocks appear mainly related to autonomic alterations.     

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.     

Different electrophysiological modes of action of oral quinidine in man

The purpose of this study was to evaluate the effects of oralquinidine on the normal sinus node (SN) and A- V node and todetermine if the drug exerts in man the same effects observedin cardiac tissue preparations (i.e. both direct and vagolyticaction). Electrophysiological studies were performed twice in each of16 patients (mean age: 57.7± 12 years) with normal restingand intrinsic heart rates and normal A-H intervals. In the firststudy, the parameters of SN and A-V node were evaluated bothin the basal state and following pharmacological autonomic blockade(AB), (propranolol 0.2 mg kg 1 and atropine 0.04 mg kg1), Oralquinidine was administered for 3–4 days (1200 mg day1)and the electrophysiological study was then repeated using thesame methods. From the comparison of data obtained in the twostudies in the basal state the overall effect of quinidine wasevaluated, and by comparing those obtained following ABthe directaction of the drug was assessed. The overall effect of quinidine on SN and A-V nodal functionswas very slight since sinus cycle length, corrected SN recoverytime, sino-atrial conduction time, A-H interval, Aj-Hj intervalat a cycle length of 600 ms and Wenckebach periods did not changesignificantly after the drug. On the contrary, following ABthese measures increased significantly (P0.01). These results provide evidence of dual effects of oral quinidinein man: a direct depressant action and an autonomically mediatedopposing action, very probably vagolytic. The overall effectof the drug is very slight.     

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

In 55 patients with persistent sinus bradycardia 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 (delta %: 65.5 +/- 33) and in group II from 51.6 +/- 5 to 73.9 +/- 14 bpm (delta %: 43.1 +/- 26). The discriminant threshold of sinus rate after atropine and its percent increase, obtained by discriminant analysis, was 80 bpm and +52%, respectively, 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.     

Effects of digitalis on the human sick sinus node after pharmacologic autonomic blockade

To study the effects of digitalis on the sinus node and the mechanisms involved, 16 patients with the sick sinus syndrome had electrophysiologic assessment of sinus nodal function during (1) control study, (2) after pharmacologic autonomic blockade with propranolol (0.2 mg/kg body weight and atropine sulfate 0.04 mg/kg intravenously), and (3) 10 minutes after 0.01 mg/kg of intravenous ouabain. The study was completed within 30 minutes of pharmacologic autonomic blockade. During the control study 50 percent of patients had an abnormal corrected sinus nodal recovery time or abnormal sinoatrial conduction time, or both. The effects of ouabain on sinus nodal function were compared with those after pharmacologic autonomic blockade. Ouabain significantly increased both intrinsic sinus cycle length (ouabain 975 ± 194 ms [mean ± standard deviation]; autonomic blockade 1,025 ± 218 ms, probability [p] < 0.001) and corrected sinus nodal recovery time (ouabain 615 ± 503 ms; autonomic blockade 575 ± 536 ms, p < 0.05). In contrast there was no significant change in sinoatrial conduction time after ouabain (ouabain 141 ± 56 ms; autonomic blockade 132 ± 45 ms; difference not significant). The effects of ouabain were similar in patients with both normal and abnormal sinus nodal function.These findings suggest that (1) digitalis in therapeutic doses has a depressant effect on intrinsic sinus nodal automaticity in patients with normal as well as abnormal sinus nodal function; (2) digitalis has no significant effects on sinoatrial conduction; and (3) the effects of digitalis on sinus nodal automaticity are primary and independent of its vagal and antiadrenergic effects.     

Atrioventricular nodal tachycardia with and without discontinuous anterograde atrioventricular nodal conduction curves: a reappraisal of the dual pathway concept

To illustrate the complexity of the electrophysiological behaviourof the human alrioventricular (A–V) node, two patientssuffering from A–V nodal tachycardia are described. Duringtachycardia an A–V nodal slow pathway was used for anterogradeconduction, and an A–V nodal fast pathway for retrogradeconduction. Patient 1 showed smooth A–V nodal conductioncurves in both the anterograde and the retrograde direction.Tachycardia could only be initiated by ventricular prematurebeats. No critical delay in ventriculo-atrial conduction timewas required for initiation of tachycardia. Patient 2 showedsmooth A–V nodal conduction curves at the lowest rateof pacing during atrial and ventricular stimulation. The curvesbecame discontinuous in both directions when the basic drivencyclelength was decreased. Tachycardia could only be initiated byatrial premature beats. Ventricular premature beats inducednon-sustained A–V nodal reentry that used an A–Vnodal fast pathway for anterograde conduction, and an A–Vnodal slow pathway for retrograde conduction. Accepting dualpathways in the anterograde and retrograde directions in theA–V node, means that depending upon their electrophysiologicalproperties a large number of combinations of anterograde andretrograde conduction are possible. When more than two A–Vnodal pathways are present, the number of possible combinationswill increase markedly. These considerations are of help inunderstanding electrophysiological findings in patients withA–V nodal tachycardia. They are also useful to explainthe importance of autonomic tone and the results of drug administrationin these patients.     

A clinical study of amiodarone as a single oral dose in patients with recent-onset atrial tachyarrhythmia

Forty-five patients with recent-onset sustained atrial tachyarrhythmia(mean heart rate at entry; 140.0± 3.5 beats. min^–1)associated with various cardiovascular diseases were treatedby oral amiodarone, given as a single loading dose of 25.7±0.9 mg. kg–1 body weight. Conversion to sinus rhythm wasobserved in 29 patients during the first 24 h of treatment,leading to a success rate of 64.4%. Five additional patientsconverted to sinus rhythm with continuation of oral amiodarone,(10–15 mg. kg^–1 by day) with a mean delay of 4.2days. A similar population of 27 patients (mean heart rate atentry; 140 ± 3 beats. min^–1) was treated by intravenousamiodarone, given as a bolus infusion of 3–5mg. kg^–1over 30min (mean; 41±02 mg. kg^–1), followed bya continuous infusion of 10–15mg. kg^–1 for 24 h(mean; 11.1±0.7 mg. kg^–1). Eighteen patients convertedto sinus rhythm during the first 24 h of therapy, leading toa success rate of 66.7%. Minor adverse effects of therapy wereobserved in two patients given oral amiodarone, and in sevengiven intravenous amiodarone. No major effect was observed.We suggest that amiodarone given as a single oral loading doseof 25–30mg. kg^–1 body weight is an effective, simpleand well-tolerated therapy, suitable for most patients withrecent-onset ATA.     

Direct and autonomically mediated effects of oral flecainide

This study was undertaken to determine if oral flecainide exerts autonomically mediated actions in addition to its direct depressant effect. Electrophysiologic studies were performed twice in each of 15 patients (mean age 59 years) with normal resting and intrinsic heart rate and normal A-H interval. In the first study, the variables of sinus node and atrioventricular node were evaluated both in the basal state and after autonomic blockade (propranolol 0.2 and atropine 0.04 mg/kg). Oral flecainide was administered for 4 to 5 days (200 to 250 mg daily) and the study was then repeated using the same methods. From comparison of data obtained in the 2 studies in the basal state, the overall effect of flecainide was evaluated and by comparing those obtained after autonomic blockade, the direct action of the drug was assessed. The overall effect of flecainide on sinus node was slight; sinus cycle length, corrected sinus node recovery time and sinoatrial conduction time did not change significantly after the drug. In contrast, after autonomic blockade the variables of sinosal automaticity were increased significantly (p less than 0.01). Flecainide significantly prolonged the atrioventricular node variables both in the basal state and after autonomic blockade (p less than 0.01), but the degree of increase was more marked after autonomic blockade (p less than 0.05). These data show dual effects of oral flecainide: a direct depressant action and an autonomically mediated opposing action, likely of vagolytic type.     

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.     

Clinical effects of digoxin on sinus node and atrioventricular node function after pharmacologic autonomic blockade

The effects of digoxin on sinus node and atrioventricular (AV) node function were studied in 18 patients (mean age 53.6 years) with normal intrinsic heart rates. Electrophysiologic testing was performed both during basal state and after autonomic blockade with propranolol and atropine. Full digitalization was achieved by intravenous administration of digoxin (0.02 mg/kg) given in three divided doses over a 24-hour period. The following day, after a basal recording, autonomic blockade was again induced and the study was repeated. During basal state, digoxin significantly prolonged the sinus cycle length (SCL) (p < 0.01) and the AH interval (p < 0.01). However, when the intrinsic sinus node functions were compared (i.e., the values obtained after autonomic blockade), digoxin did not produce significant changes in intrinsic SCL, corrected sinus node recovery time, and sinoatrial conduction time. No significant changes were noted even in the intrinsic AH interval and AV nodal refractory periods. These findings suggest that: (1) intravenous administration of digoxin in therapeutic doses does not produce any depression of the intrinsic functions of the sinus node and AV node; and (2) the depressant effects induced by digoxin during basal state appear to be mediated through the autonomic nervous system.     

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.     

Comparison of the effects of intravenous and oral betaxolol on antegrade and retrograde conduction in patients with atrioventricular nodal reentrant and atrioventricular reentrant tachycardia.

The electrophysiologic effects of intravenous (015 mg kg^–1)and oral (20 mg day^–1) betaxolol have been investigatedin 11 patients with atrioventricular (A-V) nodal reentrant tachycardiaand eight patients with orthodromic A-V reentrant tachycardia.Betaxolol significantly (P > 001) prolonged sinus cycle length,sinus node recovery time, intranodal conduction time, and theantegrade functional refractory period of the A-V node. Whenthe effective refractory period of the A-V node could be determinedit was increased by betaxolol, whereas no significant electrophysiologiceffects were observed in the atrium, the ventricle or the accessorypathway. Intravenous betaxolol prevented tachycardia in 8 outof 11 patients with A-V nodal reentrant tachycardia, whereasoral betaxolol was effective in 10 patients, primarily by actingon the antegrade limb in two patients and on the retrogradelimb in eight patients. In those with A-V reentrant tachycardia,intravenous betaxolol did not prevent tachycardia in any patient,while it was effective after oral treatment in two patients.When the tachycardia remained inducible, cycle length of thetachycardia increased in all patients, due to prolongation ofthe antegrade and retrograde conduction time in patients withA-V nodal reentrant tachycardia, and due to an increase in theantegrade conduction time, i.e. the A-V node, in the patientswith A-V reentrant tachycardia. In conclusion, betaxolol provedto be effective in the treatment of supraventricular tachycardia;for chronic treatment, a single oral dose (20 mg) seems to suffice.     

Electrophysiology of normal anterograde atrio-ventricular conduction with and without autonomic blockade

The electrophysiological measures of atrio-ventricular (A-V)conduction were investigated in 20 normal subjects (mean age:43.9±15.7 years) both during basal state and after pharmacologicalautonomic blockade. In the basal state A-H and H-V intervals and H wave durationranged from 55–110 ms (mean 83 ±15.9), 35–45ms(mean 39.5±3.9) and 10–20ms (mean 17±4.1),respectively. The lowest atrial rate inducing Wenckebach periodsranged from 150–200 beats min^-1 (mean 176.5±13.8).The effective refractory period (ERP) and the functional refractoryperiod from FRP) of the atrium ranged from 160–260 ms(mean 211±26.7) and 210–280 ms (mean 252.5 ±21.2),respectively. The ERP and the FRP of the A-V node were in theranges 230–310 ms (mean 269.3±27.2) and 330–450ms (mean 395±41.2), respectively. After autonomic blockade the H-V interval and the H wave durationdid not change in any subject The A-H interval was in the range55–105 ms (mean 82.5±15) and the lowest atrialrate inducing Wenckebach periods 150–220 beats min^-1 (mean179.5±13.5). The ERP and the FRP of the atrium rangedfrom 170–270ms (mean 215.5±28.3) and 210–300ms(mean 254±27.2), respectively. The ERP and the FRP ofthe A-V node were in the ranges 220–320 ms (mean 260.8±32)and 330–440 ms (mean 383.3±43.7), respectively.The A-V node variables did not change significantly followingautonomic blockade. These data indicate that: the definitionof normal values of A-V node measurements after autonomic blockadeallow us to evaluate the role of the autonomic nervous systemin the patients with A-V node conduction disturbances; in thebasal state the normal values of A-V conduction variables weobtained, of refractory periods in particular, are shorter thanthose previously reported; this appears to be related to thestrict criteria we used in subject selection.     

Electrophysiological effects of intravenous prostacyclin in man

The electrophysiological effects of prostacyclin (PGI₂) werestudied in 10 normal patients. Programmed stimulation was performedbefore and after infusion of 2.5, 5, 10ng kg^–1 min^–1of PGI₂. Then, 0.2 mg kg^–1 of propranolol was added tothe higher dose of PGI₂.We observed a net decrease of the systolicand diastolic arterial blood pressure beginning with the lowestdose. There was no effect on sinus node recovery time, atrial,His-Purkinje and ventricular effective refractory periods, AHand HV intervals. Atrioventricular (AV) nodal effective andfunctional refractory periods could be measured in 5 patientsand were decreased in all cases. Sinus cycle length and anterogradeand retrograde Wenckebach cycle lengths were significantly decreasedby PGI₂ in a dose dependant manner. The injection of propranololincreased all these values but did not suppress entirely theeffects of PGI₂.In conclusion, the electrophysiological effectsof PGI₂ were marked decreases of sinus cycle length and AV nodalrefractoriness which may be partly related to enhanced sympatheticactivity.     

Effects of intravenous sotalol, aprindine and the combination of sotalol and aprindine on chronic high frequency ventricular arrhythmias in man

The comparative aniiarrhythmic efficacy of three different intravenousdrug regimens was evaluated in 12 symptomatic patients (meanage: 72 years) with chronic high frequency ventricular arrhythmias(mean: 834 PVCs h^–1). In a cross-over study with latinsquare distribution the following drug regimens were administeredintravenously to all patients (a) aprindine 2 mg kg^–1,(b) sotalol 1.5 mg kg^–1, (c) aprindine 1 mg kg^–1& sotalol 0.75 mg kg^–1. The mean percentage of PVCreduction was 41% (P <0.05) for aprindine 2 mg kg^–1;51% (P <0.05) for sotalol 1.5 mg kg^–1 and 72% (P <0.01)for the combined drug therapy (aprindine 1 mg kg^–1 andsotalol 0.75 mg kg^–1). The mean plasma concentration was1371 ng ml^–1 after administration of aprindine 2 mg kg^–1and 1730 ng ml^–1 after infusion of sotalol 1.5 mg kg^–1.After combined drug therapy, mean plasma levels were 942 ngml^–1 for aprindine and 992 ng ml^–1 for sotalol.The different drug regimens were well tolerated in all patientsand no side-effects occurred. Combination therapy consistingof a drug that prolongs action potential duration with an antiarrhythmicagent that has a high affinity for the inactivated channelsmay thus achieve an antiarrhythmic efficacy comparable to singleagent therapy, permitting the use of lower dosages.     

Effect of site, summation and asynchronism of inputs on atrioventricular nodal conduction and refractoriness

The impulses coming from the sinus node synchronically penetratethe A V node via the crista terminalis and inter-atrial septum.Studies in superfused rabbit AV preparations suggest that thecrista terminalis is a more effective input than the inter-atrialseptum, and that the summation of both inputs facilitates AVnodal conduction. The aim of this study was to verify the hypothesisin a more physiological model, such as the whole rabbit heartperfused by a Langendorff system. Fifteen rabbit hearts were studied in a Langendorff perfusionsystem with six bipolar extracellular electrodes: two for stimulating(crista terminalis and inter-atrial septum) and four for recording(crista terminalis, inter-atrial septum, His bundle electrogramand right ventricle). Seven hearts (Group I) were consecutivelypaced at the crista terminalis, inter-atrial septum and bothsites simultaneously, to determine the AV nodal Wenckebach cyclelength and effective refractory period under basal conditionsand after acetylcholine (0.75 x 10^–6 M). In eight heartsunder 0.75 x 10^–6 M acetylcholine (Group II), the cristaterminalis and inter-atrial septum were simultaneously (delay= 0 ms) or sequentially (delay = 2,4, 6,8,10,12,14,and 16 ms)stimulated to calculate the AV nodal effective refractory periodand the AH interval at an atrial coupling interval 5 ms longerthan the AV nodal effective refractory period, for each delaytested. There were no basal differences in AV nodal parameters duringcrista terminalis pacing, inter-atrial septum pacing or simultaneousstimulation in both sites in Group I; after acetylcholine, theAV nodal Wenckebach cycle length and effective refractory periodtended to be shorter during crista terminalis pacing (cristaterminalis = 188 ±33 and 147±34; inter-atrialseptum = 195±35 and 158±35; both sites = 195±34and 154±36; values expressed in cycle length of pacing-ms),although the differences did not reach statistical significance.In Group II, the AH interval tended to prolong slightly on increasingthe delay between crista terminalis and inter-atrial septumstimulation (delay 0 = 119±31, 2 = 125±29, 4 =129±33,6 = 129±29,8 = 128±30,10 = 134±34,12= 132±35,14 = 129±32,and 16 = 131 ±31 ms),butagain the differences did not reach statistical significance;the A V nodal effective refractory period did not change whenthe delay was varied. Conclusions: (1) Neither the input site nor the synchronoussummation of inputs plays an important role in A V nodal conduction.(2) These results suggest that A Vnodal response during atrialtachyarrythymias depends more on atrial rate than on shiftingsin site and time coupling of inputs.     

Comparison of flecainide and procainamide in cardioversion of atrial fibrillation

In this prospective, controlled and randomized cross-over studywe tried to establish the efficiency and safety of flecainidevs procainamide for the treatment of acute atrial fibrillation.Eighty patients (30 females, 50 males, mean age: 55 ±14 years) were included. Patients entered into the study ifthey had atrial fibrillation of recent onset (<24 h) witha ventricular rate >100 beats. min^–1 at rest and were<75 years of age. Exclusion criteria were any sign of heartfailure, conduction disturbances, sick sinus syndrome or acuteischaemic events. Randomly 40 patients received flecainide and40 procainamide as the first treatment. There were no significantclinical dfference between the two groups. Procainamide wasgiven at a dose of 1 g infused over 30 min, and followed byan infusion of 2 mg.min^–1 over 1 h. Flecainide was givenat a dose of 1.5 mg.kg^–1 over 15 min followed by an infusionof 1.5 mg.kg^–1 over 1 h. Drug infusion was continued untilmaximal dose, intolerance or reversion to sinus rhythm. After1 h of wash out, patients remaining in atrial fibrillation werestarted on the second drug. Left atrial size was measured byecho. Serum levels of drug and atrial size did not dffer betweenpatients who returned to sinus rhythm and those who remainedin atrial fibrillation. Conversion to sinus rhythm was achieved in 37 (92%) of the 40patients treated with flecainide and 25 (65%) of those treatedwith procainamide (P<0.001). The time required for reversionto sinus rhythm was similar between the two groups. Flecainideis a highly effective drug, superior to procainamide, for thetreatment of paroxysmal atrial fibrillation.     

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

An electrophysiological study of sinus node function, includingmeasurements of resting heart rate, maximal corrected sinusnode recovery time and sinoatrial conduction time, was performedin 30 patients, 12–79 years of age, without any clinical,electro car diographic or electrophy siological evidence ofsinus node disease. To analyse autonomic influences, variables were measured beforeand after sympathetic and parasympathetic blockade. No significantcorrelations were observed between age and electrophysiologicalmeasurements of sinus node function at the control study orafter sympathetic blockade. In contrast, the electrophysiologicalparameters of intrinisic sinus node activity were correlatedwith age and showed a progressive lengthening of mean sinuscycle length, of maximal corrected sinus node recovery timeand of sinoatrial conduction time. In addition, measurements after vagolysis suggest a progressivedecrease of parasympathetic activity with increasing age. These data also indicate that the respective role of the twocomponents of the autonomic nervous system vary with increasingage: parasympathetic activity predominates in younger subjects;sympathetic and parasympathetic tones are equilibrated in oldersubjects. The normal sinus node function represents an equilibrated system:in parallel with ageing of the intrinsic properties of the sinusnode, parasympathetic activity decreases so that basal propertiesremain stable throughout life.     

Induction and the possible mechanism of ventricular tachycardia after catheter ablation with direct current shocks in dogs

Cathodal DC shocks (150-J) were administered via the His bundleto 20 closed-chest dogs, and in a further three dogs 25-J cathodalshocks were given via the left ventricular endocardium. In 18dogs, including three that underwent left ventricular ablation,Holter electrocardiograms were recorded from 1 to 7 days afterablation, and 4 weeks after ablation. There were frequent episodesof sustained ventricular tachycardia (VT) from the first fewhours after ablation to 4 days after ablation in all dogs, butboth the rate and the coupling interval of VT were variable.In five conscious dogs stimulated 1 day after ablation, it wasdifficult to induce and terminate VT repeatedly. There was adirect relationship between the paced cycle length and the intervalof the last paced beat to the initiating VT beat in three outof four dogs. In the fourth dog there was an inverse relationship.There was no transient entrainment with ventricular burst pacingduring VT in any of the four dogs tested. The effects of lidocaine(2–3 mg.kg^–1), verapamil (0.2–0.4 mg.kg^–1),and propranolol (0.2 mg.kg^–1) on VT were tested within2 days of ablation in 10 conscious dogs. In general, both lidocaineand verapamil terminated VT, and propranolol slowed VT. In conclusion,VT soon after ablation possibly results from triggered activity,although abnormal automaticity cannot be ruled out.