Pharmacological Autonomic Blockade Research Articles

Heart rate responses to autonomic drugs in sick sinus syndrome. Correlation with syncope and electrophysiologic data.

To assess the influence of autonomic regulation on automaticity in patients with intrinsic sinus node dysfunction, heart rate responses to autonomic drugs were evaluated in 28 patients with sick sinus syndrome and in 8 normal subjects. Heart rates before and after intravenous administration of isoproterenol (Isp), propranolol, atropine, and methoxamine were measured. To compare the results with electrophysiologic data, heart rate and automaticity recovery time (ART) before and after pharmacologic autonomic blockade (AB) were evaluated. Seventeen patients without syncope showed a similar heart rate response after administration of Isp to that of normal subjects, but 11 patients with syncope showed a significantly lower response than patients without syncope. Responses to atropine and methoxamine were lower and response to propranolol was larger in patients as compared to normal subjects. However, no significant difference was observed between patients with and without syncope. Twelve patients showed severely prolonged max ART exceeding 5000 msec after AB. Seven of them showed preserved response to Isp and max ART before AB was significantly shorter than that after AB. The other 5 patients with lower response to Isp showed no significant change in max ART before and after AB. In conclusion, sympathetic regulation in patients with preserved response to Isp might compensate for the impaired intrinsic automaticity in preventing syncope even in patients with severely impaired intrinsic sinus node function.

Modification of sinus node function by epicardial laser irradiation in dogs.

This study tested the feasibility of neodymium:YAG laser photocoagulation of selected sinus node areas to depress sinus rate responsiveness. In 14 open-chest dogs, origin of the sinus impulse (O point) was electrically mapped from the epicardium before and during isoproterenol infusion. Epicardial laser photocoagulation was applied to the O point observed during isoproterenol infusion and stepwise to remapped new O points until a 30 +/- 5% decrease in heart rate occurred. Long-term effects were assessed by Holter monitoring and electropharmacologic testing preoperatively and up to 10 weeks or 6 months. Mean (+/- SEM) percent decreases were observed at 10 weeks in the following parameters: average 24-hour heart rate, 17.4 +/- 5.0%; maximum heart rate on Holter, 30.5 +/- 3.5%; heart rate during pharmacologic autonomic blockade, 32.7 +/- 3.5%; and maximum heart rate on isoproterenol, 23.1 +/- 4.6% (all p less than 0.01). Curves with pacemaker recovery time plotted against control cycle length remained unchanged. Holter monitoring did not show excessive bradycardic episodes even after administration of propranolol. In three control dogs (sham operation), sinus node function remained unchanged. Histologic study of the irradiated area showed replacement by inflammatory cells, fibrosis, and cartilage formation with surrounding normal cells and occasional cells resembling pacemaker-like cells at the caudal end of the sinoatrial node. This study suggests that 1) map-guided graded laser photocoagulation of sinus node regions showing earliest activation during catecholamine stimulation successfully limits maximum heart rates without causing significant bradycardia, 2) the effects are long lasting, and 3) the remaining pacemaker behaves like the sinus node. Laser modification of sinus node function could become a form of nonpharmacologic heart rate control in patients with coronary artery disease undergoing surgery and in the syndrome of inappropriate sinus tachycardia.

Effect of paced cycle length on sinus node effective refractory period before and after autonomic blockade in patients with sick syndrome

Effect of basic paced cycle length on sinus node effective refractory period was studied in 22 patients with sick sinus syndrome. Sinus node effective refractory period was measured using three different paced cycle lengths before and after pharmacologic autonomic blockade. Sinus node effective refractory period could be measured at one cycle length, at least, in 59% of the patients before blockade, however, it could be measured at two or more cycle lengths in only 18% of patients because of the chaotic response of sinus node against premature stimuli. It could be measured after pharmacologic autonomic blockade in 68% of the patients at two or more paced cycle lengths. On the other hand, the rest of the patients showed no measurable sinus node effective refractory period at any cycle length, for their sinus node effective refractory periods were shorter than their right atrial effective refractory periods. The comparison of sinus node effective refractory period at different paced cycle lengths was unsuccessful before pharmacologic autonomic blockade, while the refractory period was significantly prolonged as cycle length was shortened after blockade. We concluded that (1) sinus node effective refractory period in humans is prolonged as paced cycle length decreases, (2) the autonomic reflex is the major disturbing factor in measuring sinus node effective refractory period, and pharmacologic autonomic blockade can be usefully employed to eliminate a chaotic sinus nodal response, (3) when sinus node effective refractory period is shorter than right atrial effective refractory period, a shorter paced cycle length should be used for definite measurement of the former.

Reliability of Transesophageal Pacing in the Assessment of Sinus Node Function in Patients with Sick Sinus Syndrome

The purpose of this study was to find out whether transesophageal pacing could be utilized for assessment of sinus node function in patients with sick sinus syndrome (SSS). In 17 patients with SSS (study group) we compared the results of sinus node tests obtained both in the basal state and after pharmacological autonomic blockade by endocavitary stimulation and, 24 hours later, by transesophageal pacing. In another group of 17 patients with SSS (control group), we compared the results obtained by two endocavitary studies. In "study group", sinus cycle length (SCL) and corrected sinus node recovery time (CSRT) did not show significant differences between the two studies both in the basal state and after autonomic blockade, whereas sinoatrial conduction time (SACT) was more prolonged during esophageal pacing (P less than 0.01). In "control group", sinus node measures did not show significant differences between the two studies. In the "study group," the following coefficients of correlation were obtained in the basal state; SCL, r = 0.65, CSRT, r = 0.57, SACT, r = 0.52 and after autonomic blockade: SCL, r = 0.95, CSRT, r = 0.62 and SACT, r = 0.53. In the basal state, the correlation for SCL and CSRT between the two studies was lower in the "study group" than in the "control group" (P less than 0.05), whereas after autonomic blockade the correlation for sinus node measures did not show significant differences between the two groups of patients. These data suggest that transesophageal study influences the autonomic tone regulating the sinus node; however, it is not responsible for important variations in sinus node measures.(ABSTRACT TRUNCATED AT 250 WORDS)

The Effects of Pharmacological Autonomic Blockade on Intraocular Pressure Changes during Insulin-Induced Hypoglycaemia in Normal Humans

The Effects of Pharmacological Autonomic Blockade on Intraocular Pressure Changes during Insulin-Induced Hypoglycaemia in Normal Humans

Acute determinants of the hangout interval in the pulmonary circulation

Previous investigations have suggested that the duration of the hangout interval is determined by long-term alterations in right ventricular systolic loading rather than the length of right ventricular systole. The factor(s) that effect short-term changes in this interval are unknown. Accordingly, we altered pulmonary artery pressure with phenylephrine and nitroprusside to achieve three peak pressures at low, medium, and high levels in each of 10 normal patients. Simultaneous biplane right ventricular volumes, high-fidelity pulmonary artery and right ventricular pressures, and pulmonary artery flow/velocity were obtained at each condition. After pharmacologic autonomic blockade (atropine and propranolol) at a constant heart rate achieved with atrial pacing (93 beats/min), peak pulmonary artery pressures differed significantly at low, medium, and high loading conditions (23 ± 3 vs 31 ± 7 vs 42 ± 6 mm Hg, p < 0.01). No associated significant change occurred in the preejection period (109 ± 24 vs 98 ± 14 vs 106 ± 21 msec) and right ventricular ejection time (298 ± 24 vs 318 ± 23 vs 316 ± 24 msec). The hangout interval differed significantly at each loading condition (43 ± 16 vs 34 ± 13 vs 23 ± 6 msec, p < 0.01) and correlated inversely with both the peak pulmonary artery pressure ( r = −0.53, p < 0.01) and the right ventricular end-systolic pressure ( r = −0.56, p < 0.01). In contrast, the hangout interval and right ventricular ejection time were not linearly related. Therefore we conclude that the hangout interval is determined short-term by the level of pulmonary vascular loading rather than the duration of right ventricular systole.

Effects of Diproteverine, a New Calcium Antagonist on Sinoatrial Node and Atrioventricular Conduction in Conscious Unsedated Dogs

The electrophysiologic effects of diproteverine were studied in the conscious nonsedated chronically instrumented dog. Diproteverine at 0.25-0.75 mg/kg (i.e., at plasma levels within the assumed therapeutic range) dose-relatedly decreases heart rate, increases corrected sinus node recovery time, and decreases Wenckebach point. These effects are observed at plasma levels ranging between 16.2 +/- 4.1 and 144.7 +/- 12.5 ng/ml. After cholinergic blockade with N-methylscopolammonium, diproteverine lowers heart rate (greater than or equal to 0.25 mg/kg), increases corrected sinus node recovery time, and decreases Wenckebach point (greater than or equal to 0.5 mg/kg). After propranolol, diproteverine only significantly reduces corrected sinus node recovery time 5 min after the third administration (0.75 mg/kg). After pharmacologic autonomic blockade by N-methylscopolammonium propranolol combination, diproteverine lowers intrinsic heart rate (greater than or equal to 0.25 mg/kg) and Wenckebach point (greater than or equal to 0.5 mg/kg). Diproteverine does not modify mean blood pressure. These results show that diproteverine administered with and without pharmacologic autonomic blockade in the conscious dog causes dose-related depressant effects on sinus node function and atrioventricular conduction without producing significant vasodilatation.

Prolongation of the QT Interval by Volatile Anesthetics in Chronically Instrumented Dogs

The influence of volatile anesthetics on ventricular repolarization in vivo (QT interval) has not been studied in a systematic fashion. The purpose of this investigation was to characterize the electrocardiographic and hemodynamic actions of the volatile anesthetics halothane, isoflurane, and enflurane in chronically instrumented dogs. Because autonomic nervous system tone may influence ECG findings, experiments were completed with and without concomitant pharmacologic autonomic nervous system blockade. In six groups comprising 50 experiments with 21 instrumented dogs, anesthesia was mask-induced with nitrous oxide, oxygen, and one of the volatile anesthetics and maintained with the volatile anesthetic in 100% oxygen for 2 hours. Changes in the ECG and in hemodynamics were compared to the conscious state. In the absence of autonomic nervous system blockade, halothane and isoflurane significantly prolonged the QT interval (0.24 +/- 0.01 to 0.30 +/- 0.01 second and 0.22 +/- 0.01 to 0.28 +/- 0.01 second, respectively), whereas enflurane produced no change in ventricular repolarization (0.24 +/- 0.01 to 0.26 +/- 0.01 second). All of the volatile anesthetics increased the QT interval corrected for changes in basal heart rate (QTc), and all agents decreased intravascular pressure and dP/dt. Following autonomic nervous system blockade, halothane, isoflurane, and enflurane significantly increased the QT interval and QTc. The results demonstrate that ventricular repolarization is directly altered by the volatile anesthetics independent of changes in autonomic nervous tone. Whether or not such effects are additive with other congenital or acquired forms of QTc prolongation has yet to be examined. The present results indicate that caution should be used during the administration of volatile anesthetics to patients with abnormalities of the QT interval.

Diagnostic value pharmacological autonomic blockade in patients with suspected sick sinus syndrome.

The study comprised 67 subjects, mean age 43.7 years, with suspected sick sinus syndrome, in whom rapid atrial pacing before and after combined atropine and propranolol was performed by Narula's method. Three groups were formed: group I--with normal sinus node recovery time (SNRT) and corrected sinus node recovery time (CNRT) before and after the autonomic blockade; group II--with functional disorders of the sinus node and group III--with intrinsic sinus node dysfunction. After autonomic blockade in groups I and II mean SNRT, CNRT, post-stimulation cycle lengths (except No. 2 and Nos. 5, 6, 10, respectively) shortened, whereas HR rose. In contrast, in group III mean SNRT, CNRT, post-stimulation cycle lengths (Nos. 1, 2, 6, 10) and HR increased. Significant differences in post-stimulation cycle lengths were observed between groups I and III as well as groups II and III. In conclusion, rapid atrial pacing after combined atropine and propranolol helps us to diagnose latent sick sinus syndrome and extrinsic sinus node dysfunction more precisely, and significant differences in post-stimulation cycle lengths between the groups confirm diagnostic value.

The cardiovascular effects of trimazosin and prazosin in the rabbit.

The cardiovascular effects of trimazosin, a quinazoline derivative similar in structure to prazosin, were investigated and compared with prazosin in the rabbit. Radioligand binding to cerebral membranes showed that trimazosin has roughly 100-fold less affinity for the alpha 1-adrenoceptor. This was further supported by its lower pA2 derived from phenylephrine contractile responses in isolated thoracic aorta preparations. Trimazosin is less extensively distributed and has a lower clearance from whole blood than prazosin although their whole blood elimination half-lives are comparable. In addition, although it is a less potent alpha 1-adrenoceptor antagonist in vivo, its peripheral vascular depressor effect tends to be greater than prazosin. Trimazosin at the dose used and under the conditions of study did not reverse the peripheral pressor effect of angiotensin II or B-HT920 but at higher concentrations, unlike prazosin, it relaxed the K+ contracted thoracic aorta. In addition, following pharmacological autonomic blockade and treatment with prazosin in vivo, trimazosin caused a further depressor response. A similar though shorter lasting non-alpha 1-receptor mediated action was also observed with prazosin. 1-Hydroxytrimazosin (CP23445), the major metabolite of trimazosin in man, showed little affinity for either the alpha 1- or alpha 2-adrenoceptor from radioligand binding studies. In addition to alpha 1-adrenoceptor antagonism, trimazosin may exert an additional direct vasodilator effect in rabbits.

Effect of pharmacologic autonomic blockade on ventriculoatrial conduction

To determine the influence of autonomic tone on retrograde ventriculoatrial (VA) conduction, incre mental atrial and ventricular pacing was performed before and after pharmacologic autonomic blockade in 28 patients. VA conduction during ventricular pacing was demonstrated, with highest frequency in patients capable of 1:1 atrioventrlcular (AV) conduction at atrial paced cycle lengths of 300 ms or less (7 of 7, 100%). In subjects with 1:1 AV conduction at minimum cycle lengths of 300 to 500 ms, 14 of 21 (67%) demonstrated VA conduction in the control state; however, only 12 of 21 (57%) did so after autonomic blockade. The lowest frequency was observed in those capable of 1:1 AV conduction at minimum cycle lengths of 505 ms or more before and after autonomic blockade (2 of 7, [29%], p < 0.02 compared with values in the first group). No change in the mean minimum ventricular paced cycle length at which 1:1 VA conduction could be maintained was demonstrated after autonomic blockade. In individual subjects, incremental change in this cycle length after autonomic blockade correlated positively with the corresponding change in minimum atrial cycle length at which 1:1 AV conduction could be maintained (r = 0.62, p < 0.005), and was concordant in direction in 18 of 21. In conclusion, the sympathetic and parasympathetic modulation of VA conduction is balanced and concordant in direction to the effect on AV nodal conduction.

Effects of hypertension and hypercholesterolemia on vasodilatation in the rabbit.

Vasodilator substances act either directly on vascular smooth muscle (e.g., adenosine) or indirectly (e.g., acetylcholine) on endothelial cells that respond by releasing an unknown powerful, short-lived relaxing factor. To determine whether chronic hypertension or hypercholesterolemia or both would alter the release of the endothelium-derived relaxing factor, experiments were performed in hypertensive rabbits (5-week cellophane wrap perinephritis; mean blood pressure, 134.7 mm Hg) and normotensive rabbits (mean blood pressure, 80 mm Hg) with a Doppler flow transducer and perivascular balloon implanted on the lower abdominal aorta. Rabbits were fed either 1% cholesterol or control diet for 4 weeks before the experiment. On the day of the experiment, resting hindlimb vascular resistance was greatest in hypertensive rabbits fed 1% cholesterol diet, followed (in descending order) by hypertensive rabbits, normotensive rabbits fed 1% cholesterol diet, and normotensive rabbits. Pharmacological autonomic reflex blockade was induced, and steady state intravenous infusion curves to acetylcholine, serotonin, and adenosine were constructed. Sensitivity (location of effective dose, 50%) to the three vasodilator agents was altered less than twofold from the values in normotensive rabbits for any treatment group. The maximum vasodilator response to acetylcholine, but not to adenosine or serotonin, infusion was reduced significantly in the treated rabbits compared with that in normal rabbits. Reactive hyperemic responses to 5 to 80 seconds of ischemia were not significantly different among the treatment groups. These results indicate that hypertension with or without hypercholesterolemia does not greatly alter the responsiveness of the hindlimb resistance vasculature to these three vasodilator agents or to ischemia.

Endothelium-dependent relaxation is unaltered by hypertension, cholesterol or intimal thickening.

The effect of cellophane wrap hypertension (WRAP) and hypercholesterolemia (1% cholesterol diet, CHOL) for 4 weeks was assessed on the endothelium-dependent vasodilator response to acetylcholine in conscious rabbits after pharmacological autonomic blockade. Dose-response curves for the hindlimb vascular resistance (ear artery pressure/lower aortic blood flow; Doppler flowmeter) and acetylcholine infusion (i.v.) doses were unaltered in sensitivity (ED50) for any of the treatment groups. The range and slope of the curves were significantly altered by WRAP, CHOL or WRAP plus CHOL for acetylcholine and adenosine infusions consistent with medial hypertrophy in resistance vessels and raised serum viscosity. The effect of intimal thickening on the response to endothelium derived relaxing factor (EDRF) was tested in dog carotid artery ring segments in vitro 4 weeks after endothelium removal. The relaxation responses to acetylcholine (EDRF-dependent) and adenosine or nitroglycerin were not significantly altered by the neo-intima. Therefore the response to EDRF released by acetylcholine in resistance vessels was unaltered by hypertension, hypercholesterolemia or both together. Neo-intimal thickening in response to initial endothelium loss does not appear to alter EDRF responses in the carotid artery.

Effects of autonomic blockade on dual atrioventricular nodal pathways pattern

Fifteen patients (age: 57.6 +/- 14 years) showing dual A-V nodal pathways pattern during basal electrophysiological testing were studied following pharmacological autonomic blockade (iv propranolol 0.2 mg/Kg and iv atropine 0.04 mg/Kg). After induction of the autonomic blockade, the dual A-V nodal pathways pattern was not present in four patients due to disappearance of the slow pathway; the pattern remained in 11 (73%). The longest A2-H2 interval, the effective and functional refractory periods of the fast pathway did not change significantly following autonomic blockade. Even the electrophysiological measures of the slow pathway, in the 11 patients in whom they were comparable, did not change significantly after autonomic blockade. These data suggest that: the dual A-V nodal pathways pattern is mainly related to the intrinsic structure of the A-V node; the autonomic nervous system only affects in a variable way the refractoriness and the conduction velocity in the two pathways.

Different electrophysiological modes of action of oral quinidine in man.

The purpose of this study was to evaluate the effects of oral quinidine on the normal sinus node (SN) and A-V node and to determine if the drug exerts in man the same effects observed in cardiac tissue preparations (i.e. both direct and vagolytic action). Electrophysiological studies were performed twice in each of 16 patients (mean age: 57.7 +/- 12 years) with normal resting and intrinsic heart rates and normal A-H intervals. In the first study, the parameters of SN and A-V node were evaluated both in the basal state and following pharmacological autonomic blockade (AB), (propranolol 0.2 mg kg-1 and atropine 0.04 mg kg-1), Oral quinidine was administered for 3-4 days (1200 mg day-1) and the electrophysiological study was then repeated using the same methods. From the comparison of data obtained in the two studies in the basal state the overall effect of quinidine was evaluated, and by comparing those obtained following AB the direct action of the drug was assessed. The overall effect of quinidine on SN and A-V nodal functions was very slight since sinus cycle length, corrected SN recovery time, sino-atrial conduction time, A-H interval, A1-H1 interval at a cycle length of 600 ms and Wenckebach periods did not change significantly after the drug. On the contrary, following AB these measures increased significantly (P less than or equal to 0.01). These results provide evidence of dual effects of oral quinidine in man: a direct depressant action and an autonomically mediated opposing action, very probably vagolytic. The overall effect of the drug is very slight.

Effects of pharmacologic autonomic blockade on atrial electrophysiologic properties in normal subjects and in patients with sinus node disease

In order to elucidate the influence of autonomic nervous system on atrial electrophysiologic properties, we studied 10 patients with sinus node dysfunction and 10 age-matched normal subjects. In each of them effective and functional refractory periods of the right atrium (near its junction with the superior caval vein) were measured, during atrial pacing (100/min) and using variable current strengths (2, 3, 4, 5, 7,1 0, and 15 mA), before and after pharmacologic autonomic blockade (using intravenous propranolol 0.2 mg/kg and atropine 0.04 mg/kg). Mean values of effective and functional refractory periods at each current strength were significantly higher in patients with sinus node disease than in normal subjects both before and after autonomic blockade. Blockade did not significantly modify mean values of effective and functional refractory periods at any current strength, either in patients with sinus node disease or in normal subjects. Furthermore, autonomic blockade did not change the effects of the increase of current strength on atrial refractoriness in either group. We conclude that our data indicate a prolonged refractoriness to be present in patients with sinus node disease even in the absence of influences from the autonomic nervous system. Thus, we can suggest a “primary” involvement of atrial fibers in this pathophysiological condition. Propranolol together with atropine did not induce changes of atrial refractoriness. Indeed, they probably exerted an opposite effect. The effects of the increase of current strength on atrial excitability do not seem to be mediated by autonomic humoral agents.

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 pharmacological autonomic blockade. In the basal state A-H and H-V intervals and H wave duration ranged from 55-110 ms (mean 83 +/- 15.9), 35-45 ms (mean 39.5 +/- 3.9) and 10-20 ms (mean 17 +/- 4.1), respectively. The lowest atrial rate inducing Wenckebach periods ranged from 150-200 beats min-1 (mean 176.5 +/- 13.8). The effective refractory period (ERP) and the functional refractory period 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 the ranges 230-310 ms (mean 269.3 +/- 27.2) and 330-450 ms (mean 395 +/- 41.2), respectively. After autonomic blockade the H-V interval and the H wave duration did not change in any subject. The A-H interval was in the range 55-105 ms (mean 82.5 +/- 15) and the lowest atrial rate inducing Wenckebach periods 150-220 beats min-1 (mean 179.5 +/- 13.5). The ERP and the FRP of the atrium ranged from 170-270 ms (mean 215.5 +/- 28.3) and 210-300 ms (mean 254 +/- 27.2), respectively. The ERP and the FRP of the 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 following autonomic blockade. These data indicate that: the definition of normal values of A-V node measurements after autonomic blockade allow us to evaluate the role of the autonomic nervous system in the patients with A-V node conduction disturbances; in the basal state the normal values of A-V conduction variables we obtained, of refractory periods in particular, are shorter than those previously reported; this appears to be related to the strict criteria we used in subject selection.

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.

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 node dysfunction. We compared primary and secondary atrial postpacing pauses and postextrasystolic sino-atrial responses before and after autonomic blockade in 56 patients with the clinical diagnosis of sick sinus syndrome. Pharmacological autonomic blockade was achieved by atropine 0.04 mg kg-1 and propranolol 0.2 mg kg-1, i.v. In a group of patients with a normal intrinsic heart rate the number of positive electrophysiologic variables associated with sinus node dysfunction declined after autonomic blockade. In 91% of these patients, sinus node function was characterized by a normal intrinsic recovery time, gradual exponential return to the constant sinus cycle length, and biphasic postextrasystolic return responses. Three patients in this group had intrinsic SA-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 as manifested by bradycardia and the tachycardia-bradycardia syndrome. SA-block and sinus arrest up to 29120 ms. In the abnormal intrinsic heart rate group, disturbed intrinsic rhythmicity was characterized in all by a prolonged corrected intrinsic recovery time (2320 +/- 2740 ms [+/- SD]), arrhythmia and/or bradycardia in the secondary postpacing cycles, chaotic postextrasystolic patterns, or prolonged sinoatrial conduction times. Significantly slow minimal heart rates during sleep significantly prolonged average sinus cycle lengths and positive ECGs for sinoatrial disorders in the waking period were present on the 24-h rhythm recording. It is concluded that intrinsic heart rate obtained by autonomic blockade is the best and most simple method for the diagnosis of intrinsic sinus node dysfunction. Combined autonomic blockade and electrophysiological tests can be of great value in unmasking the severity and degree of intrinsic dysfunction and analyzing the abnormality of secondary pacemaker function. These investigations, however, are rather insensitive and therefore ineffective in detecting autonomic sinus node dysfunction. To assess the role and significance of the autonomous neurovegetative tone in the genesis of sinoatrial disorders, rhythm monitoring is required.

Enhanced atrioventricular nodal conduction in man: electrophysiologic effects of pharmacologic autonomic blockade.

Enhanced atrioventricular nodal conduction (EAVC) comprises a portion of the spectrum of atrioventricular node electrophysiology in which physiologic slowing of atrioventricular conduction is diminished. To evaluate the basis of EAVC in humans, we compared the effect of pharmacologic autonomic blockade on electrophysiologic characteristics of atrioventricular nodal conduction and refractoriness in 10 patients with EAVC and 12 patients without EAVC (non-EAVC). The effects of autonomic blockade (0.2 mg/kg iv propranolol and 0.04 mg/kg iv atropine) on sinus cycle length and atrial refractory period were similar in both EAVC and non-EAVC patients. After autonomic blockade, minimum atrial paced cycle length with 1:1 atrioventricular conduction lengthened in EAVC patients (control, 268 +/- 25 msec; blockade, 307 +/- 34 msec; p less than .01), but remained unchanged in non-EAVC patients (control, 392 +/- 69 msec; blockade, 382 +/- 49 msec; p = NS). Similarly, atrioventricular nodal functional refractory periods tended to lengthen in EAVC patients, while remaining unchanged or shortening in non-EAVC patients. Furthermore, although autonomic blockade reduced differences between EAVC and non-EAVC patients, both minimum cycle length with 1:1 atrioventricular conduction and atrioventricular functional refractory period remained shorter in EAVC than in non-EAVC patients (p less than .02). Thus, baseline differences in autonomic atrioventricular nodal control differ in EAVC and non-EAVC patients, but do not fully account for differences in atrioventricular nodal electrophysiologic properties in these patients. Consequently, underlying structural functional factors may play an important role in determining the range of atrioventricular nodal electrophysiologic characteristics in man.