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.     

Latent abnormalities of sinus node function in patients with organic heart disease and normal sinus node on clinical basis

Sinus node (SN) function was analyzed in 22 patients (mean age: 46.2±12.9 years) with organic heart disease and normal SN on clinical basis (group I) and in 20 normal subjects (mean age: 43.9±15.6 years), (control group). Sinus cycle length (SCL), corrected sinus node recovery time (CSRT) and sinoatrial conduction time (SACT) were analyzed. After the control study, autonomic blockade (AB) was induced by i.v. propranolol (0.2 mg/Kg) and atropine (0.04 mg/Kg). Measurements of SCL, CSRT and SACT were then repeated. The mean SCL values were very similar in the two groups during the control state and after AB. There were no significant differences in SACTs between the two groups during the control state or after AB. On the contrary, the CSRT of group I was significantly longer than that of control group during the control state (344.8±78.9 versus 262.2±46.3 msec, P<0.001) and after AB (238.9±72.8 versus 166.8±39.3 msec, P<0.001). The analysis of real depression of SN automaticity (CSRT minus SACT) in the two groups shows that prolongation of CSRT in group I during the control study and after AB is related to an intrinsic abnormality of SN automaticity; on the contrary, no dysfunctions of the autonomic nervous system appear. These data indicate that the intrinsic abnormality of SN automaticity represents the earliest in volvement of the SN in subjects with organic heart disease and normal SN on clinical basis, although this conclusion is speculative and requires experimental verification.     

Left bifascicular block with normally conducting middle fascicle

A case of aortic insufficiency showing an ECG pattern of left ventricular hypertrophy and strain has been followed over time. One year after the initial observation, the ECG and VCG recordings showed the appearance of a left bifascicular block, due to involvement of the anterior and posterior fascicles, with normal septal activation. It is suggested that the normally functioning middle fascicle activates the inferior two-thirds of the septum. This hypothesis is discussed in light of recent experimental data.     

Left ventricular parietal block: diagnostic and clinical study.

Fifty-five patients with widened QRS complexes due to the presence of slurred S waves or of terminal slurrings on R waves, in more than three leads, with no infarction or bundle branch and fascicular blocks, were studied with the usual clinical examinations as well as vectorcardiographic recording. A parietal block of the left ventricle was diagnosed when, in the presence of a normal development of ventricular depolarization in the initial and middle phases, the terminal QRS loop was delayed, sometimes irregular and displaced leftward and posteriorly. When this delay was directed to the right, the ventricular localization was puzzling. The comparison of the electrocardiographic (ECG) and vectorcardiographic (VCG) data on the terminal part of ventricular depolarization showed some discrepancies and revealed the greater importance of VCG investigation for the study and the localization of parietal blocks. The pathogenesis of such minor conduction disturbances is not yet clear, since the experimental data on the anatomical-functional structures are different: the Purkinje network, Purkinje fiber-muscle junction or common myocardium. In some cases we think it is possible to localize the structure concerned; in any case we can always localize it at the level of the free ventricular wall.     

Effects of dobutamine on electrophysiological properties of the specialized conduction system in man

The electrophysiological effects of Dobutamine, a new beta adrenergic drug, were investigated using intracardiac electrograms and the extrastimulus method, in 19 patients with 1:1 AV conduction and in 10 other patients, five with second and five with third degree AV block. The electrophysiological effects were studied at three concentrations of the drug: 5, 10 and 15 micrograms/Kg/m'.Dobutamine induces: 1) an enhancement of SA node automaticity, showed by a decrease of the sinus cycle length (P less than 0.001 at the first concentration) and by a decrease in the corrected sinus node recovery time (P less than 0.001 at the second concentration); 2) a decrease in the effective atrial refractory period (P less than 0.001 at the first concentration); 3) an improvement of AV conduction, showed by a decrease in AH interval (P less than 0.001 at the first concentration) and by a shortening of functional and effective refractory periods (P less than 0.001 at the first concentration); 4) no change in the HV interval; 5) an improvement of conduction in patients with second degree AV block proximal to the His bundle; and 6) a minimal increase in the heart rate in patients with complete AV block distal to His bundle.     

Effects of amiodarone on supraventricular tachycardia involving bypass tracts

This study evaluates whether the electrophysiologic effects of i.v. amiodarone in patients with reentrant supraventricular tachycardia (SVT) can predict the efficacy of long-term oral therapy with this drug. The effects of oral and i.v. amiodarone were studied in 27 patients with SVT. In 14 the SVT circuit involved a concealed atrioventricular bypass for retrograde conduction (Group I), and in 13 a concealed atrio-His bypass (Group II). Intravenous amiodarone induced significant prolongation of the AH interval, the refractory periods of the atrium, atrioventricular node, His-Purkinje system and ventricular myocardium. The ventriculoatrial interval was slightly prolonged in Group I patients and did not change in Group II patients after i.v. administration of the drug. In both groups, the effective refractory period (ERP) of the concealed bypass was prolonged by i.v. amiodarone.During control state, SVT could be induced in all patients; after i.v. administration of the drug, SVT was presented in 6 patients in Group I and in 8 patients in Group II. In all cases, in which i.v. amiodarone prolonged the ERP of the concealed bypass to more than 350 ms, the drug always prevented SVT even when given orally. All but 2 patients—1 from Group I and 1 from Group II—remained asymptomatic after oral amiodarone. In the patient from Group I, SVT had been prevented by i.v. amiodarone, whereas in the patient from Group II SVT could not be induced by ventricular stimulation during the control state, but appeared after i.v. administration of the drug.These data indicate that (1) therapy with oral amiodarone is effective in most patients with SVT irrespective of the type of bypass fibers, i.e., atrio-His or Kent bundle; (2) effective suppression of induction of SVT with i.v. amiodarone is a predictor of efficacy of amiodarone in 93 % of the cases. However, a lack of response to i.v. amiodarone is not a predictor of lack of efficacy of oral amiodarone; (3) prolongation of the ERP of the concealed bypass tract to > 350 ms appears to have a favorable predictive value in oral administration; (4) a change in the inducibility of SVT after i.v. amiodarone appears to have a negative predictive value in controlling SVT with the oral drug.     

Endocardial electrogram amplitudes and stimulation thresholds in monopolar electrodes: Possible correlations

The possible correlations between unipolar endocardial electrogram amplitudes and voltage threshold stimulation were tested with electrodes having metallic tips of two different areas. The threshold measurements were always studied with the same pulse characteristics.The data were analyzed through five mathematical functions (linear, exponential, potential, hyperbola and translate hyperbola). The results show a significant correlation, mainly by hyperbolic and exponential functions. Consequently, we could deduce a parameter value since we already knew the other one. This was possible not only during the first implantation, but also later on.     

Autonomic tone of patients during an electrophysiological catheterization: The role of autonomic influences on the reproducibility of sinus node function studies

Urinary catecholamine excretion remained unchanged and total electromechanical systole, QS₂I, increased during the electrophysiological study of 16 patients (eight normals, eight with sinus node dysfunction) when compared to values obtained the day before and the day after the study. The mean values of the sinus node function studies (sinoatrial conduction and recovery times) repeated the day after the procedure were not significantly different from those obtained during the electrophysiological study in both the normal patients and patients with sinus node dysfunction. Individual patients in the sinus node dysfunction group showed slight variation in the sinus node studies; four of these patients showed normalization of SA node function the day after the electrophysiological procedure.These studies suggest that the electrophysiological procedure does not provoke a hyperadrenergic state. The sinus node function studies are reproducible in patients with normal baseline values. While the mean sinus node function results for the group with abnormal SA node function did not change significantly on repeat testing, some individual variation occurred; this variation is probably related to autonomic disturbances of SA node function.     

Effect of verapamil on normal sinoatrial node function and on sick sinus syndrome

Sixty patients, normal with respect to SAN function, screened to exclude cardiomyopathy, and seven patients with sick sinus syndrome underwent overdrive right atrial pacing at progressively increasing rates before and after administration of different doses of verapamil. Sinoatrial node corrected recovery time and per cent recovery time related to control PP were determined before and five, 15, and 30 minutes after the administration of the drug. Moderate prolongations of these parameters lasting for more than 30 minutes were observed with doses of 0.15 and 0.20 mg./Kg. of verapamil, evidencing a depressant effect on normal SAN function; concomitant and earlier AV conduction impairment was also observed. These changes were dose-related, and were eliminated by administration of isoproterenol, but not by atropine intravenously. Action of the drug is probably exerted directly on SAN and AVN cells, since it did not show any significant effect on beta-sympathetic receptors or on cholinergic receptors.In patients with sick sinus syndrome, effect of verapamil on SAN function is four or five times more intense, with concomitant impairment of AVN function; several of these patients had prolonged asystoles after administration of the drug which did not reverse with atropine injection. It is concluded that the marked depression of SAN function caused by verapamil in patients with sick sinus syndrome contraindicates its use for treatment of any of the atrial arrhythmias which form this syndrome. Precautions must be taken also when treating any supraventricular arrhythmia on an emergency basis, since they may be caused by an as yet undiagnosed sick sinus syndrome.     

Electrophysiologic effects of procainamide on sinus function in patients with and without sinus node disease

To compare the effects of procainamide on sinus node (SN) function in the presence (seven patients) and absence (nine patients) of SN dysfunction, sinus cycle length (SCL), maximal corrected sinus recovery time (maximal CRST), paced cycle length yielding peak SN suppression (PCLp), and indirect sinoatrial conduction time (SACT) were determined before and after intravenous administration of 10 to 15 mg/kg procainamide in each patient. Plasma procainamide concentration was in the therapeutic range in all patients. The mean SCL did not change significantly in either group (?24 ± 58 and ?73 ± 171 msec for patients with normal and abnormal SN function, respectively). The maximal CSRT shortened 136 ± 112 msec (p < 0.01) in the group with normal SN function (nine of nine patients) but tended to lengthen 85 ± 95 msec (p < 0.10) in the group with SN dysfunction (six of seven patients). PCLp shortened in only two of nine of the normal group but tended (NS) to shorten in five of seven patients with SN dysfunction. We conclude that in the absence of SN disease, procainamide does not adversely affect SN function. In apparent contrast in patients with SN dysfunction, procainamide tended (NS) to prolong CSRT and seemed (NS) to enhance conduction in the sinoatrial junction (PCLp and SACT both declined). The occasional lengthening of CSRT implies that procainamide might prolong post-tachycardia pauses and thus could worsen symptoms in certain patients with the bradycardia-tachycardia syndrome.     

Verapamil effects in AV node reentry tachycardia with intermittent supra-Hisian AV block

The electrophysiologic details of two patients with atrioventricular (AV) node reentry tachycardia with intermittent 2:1 supra-Hisian block are presented. Both patients had clear evidence for atrial arrhythmias as well, emphasizing the need for a careful diagnostic analysis. Evidence supporting a diagnosis of AV node reentry tachycardia included: (1) short ventriculoatrial (VA) coupling intervals, (2) normal retrograde sequence of atrial activation, (3) dependence on critical AV node conduction times for initiation of tachycardia by atrial pacing, (4) ability to pace and capture the atria or ventricles without interrupting the tachycardia, and (5) fixed VA coupling intervals despite changes in tachycardia cycle length. Ten milligrams of verapamil was administered during sustained supraventricular tachycardia with 1:1 AV conduction, but despite prompt termination of tachycardia in both cases, 2:1 AV block was not induced. Atrial echoes could still be induced after verapamil, and diagnostic features (3) and (5) were particularly evident after the drug. Further analysis confirmed that verapamil did not have any observable effects on the likely site for supra-Hisian block—that is, the “final common pathway” of the AV node. This would support a contention that verapamil may have a selective effect on tissues within the confines of the AV node.     

Prolactin and growth hormone responses to dermorphin in patients with prolactin-secreting pituitary adenoma

We have recently shown that dermorphin (D), a new potent opioid peptide (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2) stimulates prolactin (PRL) and growth hormone (GH) secretion in humans. In 11 patients with a PRL-secreting pituitary adenoma (eight microprolactinomas and three macroprolactinomas with suprasellar extension), diagnosed by pituitary dynamic function tests, and radiological evidence with confirmation at surgery, the PRL and GH responses to D were studied to evaluate the effect of pathological hyperprolactinemia on the opioid-induced secretion of GH and PRL. No PRL response to D was observed in all 11 patients. Plasma GH increased after D in all patients, except in three patients bearing a macroprolactinoma. This study shows that the effect of D on PRL and GH secretion can be dissociated in patients with PRL-secreting pituitary adenoma, perhaps for a different derangement in the hypothalamic-pituitary mechanism(s) underlying the opioidergic regulation of GH and PRL secretion. In addition our data indicate that D can be employed as a useful opioid probe in humans.     

Electrophysiologic effects of hydralazine on sinoatrial function in patients with sick sinus node syndrome

The electrophysiologic effects of hydralazine were evaluated in nine hypertensive patients with sinoatrial dysfunction. Intravenous hydralazine, 0.15 mg/kg, caused no significant reduction in arterial blood pressure. Yet this dose of hydralazine increased heart rate from 61.9 +/- 4.1 beats/min (mean +/- standard error of the mean) to 68.6 +/- 4.9 (P less than 0.001). Sinus nodal recovery time upon termination of atrial pacing shortened from 3,207 +/- 1,098 to 2,064 +/- 573 msec (P less than 0.05) and second escape cycles shortened as well (P less than 0.025). Acceleration of heart rate and abbreviation of recovery time did not closely correlate with change in blood pressure (r = 0.41 and 0.18, respectively). Junctional escape beats became more frequent and junctional escape time shortened from 2,525 +/- 692 to 1,705 +/- 382 msec (P less than 0.05). Sinoatrial conduction time tended to shorten, but a significant change was not observed. Atrial tachyarrhythmias did not occur and atrial refractoriness was unchanged. Thus, a minimal blood pressure response to hydralazine was associated with enhanced automaticity. Hydralazine merits clinical trial for treatment of sick sinus syndrome with concomitant hypertension.     

The conduction system in rheumatoid arthritis with complete atrioventricular block.

Rheumatoid arthritis, of the peripheral type, or the ankylosing spondylitis type, with complete atrioventricular (A-V) block^1–11 or other conduction disturbances^12–18 has been sporadically reported. Very few conduction system studies have been done in these cases.^{3, 7–9, 17, 18} The present report deals with a comprehensive serial section study of the conduction system in a case of the peripheral type of rheumatoid arthritis with complete A-V block.     

Permanent pacing in disorders of sinus node function

Thirty-three patients with disorders of sinus node function treated with permanent endocardial pacemakers were evaluated. Study of the underlying heart rate and rhythm was accomplished by external inhibition of pacemakers. The development of stable atrial fibrillation was documented in 7 out of 29 patients studied and effectively terminated the syndrome of sinus node dysfunction. Embolic complications appeared to be an important factor in the morbidity and mortality in patients with changing supraventricular rhythms. Pacemaker therapy effectively controlled syncopal episodes due to bradycardia, but recurrent episodes of tachycardia and problems associated with this remained unaffected.     

Exercise assessment of sinoatrial node function following the Mustard operation

To screen for sinoatrial node dysfunction following the Mustard procedure for transposition of the great arteries, we studied the chronotropic response to graded maximal treadmill exercise in 29 patients at mean 6.7 years after operation. Although 93% of patients had normal resting heart rate (HR), 83% demonstrated significant depression of maximum HR and/or recovery HR after termination of exercise. These findings were similarly present among a subset of 13 patients with normal exercise tolerance. Resting and exercise-induced HR in 10 patients receiving chronic digoxin therapy were no different than in the 19 patients without medication. Sixteen patients with abnormal chronotropic responses to exercise had intracardiac electrophysiologic evaluation which confirmed sinoatrial node dysfunction in nine. Abnormal HR responses did not correlate with clinical symptoms, cardiac arrhythmias, or postoperative hemodynamics. Maximal exercise testing may be a sensitive noninvasive method to identify sinoatrial node dysfunction in postoperative children.