Effect of amiodarone on retrograde conduction and refractoriness of the His-Purkinje system in man

Fourteen previously reported cases of atresia of the coronary sinus ostium, in which the coronary venous flow entered the right atrium by a persistent left superior vena cava, the innominate vein, and the right superior vena cava, are reviewed and two new cases reported. The first new case was in a 43 year old woman with atypical chest pains in whom investigations for suspected ischaemic heart disease, including coronary arteriography, yielded normal results. She died suddenly from massive myocardial infarction due to extensive old thrombotic occlusion of a major coronary artery without any appreciable underlying disease of the vessel wall. Exercise testing is considered to be advisable in symptomatic patients with normal coronary angiograms and attention to the venous phase might be informative. The second new case occurred in a child with an atrial septal defect and complete transposition of the great arteries, who died aged 1 month.     

Effect of lidocaine on conduction in the ischemic His-Purkinje system of dogs

The effect of lidocaine on His-Purkinje conduction in dogs with ischemic damage to the His bundle was compared with the effect of lidocaine in normal dogs. The anterior septal artery was ligated in 14 dogs, and 30 minutes later atrial pacing was performed to increase residual ischemic damage. Four to 6 days later, His bundle recordings were obtained during sinus rhythm and atrial pacing before and after the administration of lidocaine in a dose of 2 mg/kg and a total dose of 4 mg/kg. His bundle recordings were also obtained in nine control animals before and after the administration of lidocaine. Lidocaine significantly increased the H-V time in the animals with ischemic damage during sinus rhythm and at all pacing rates. It also resulted in advanced His-Purkinje conduction defects including His bundle block and right bundle branch block in these animals. In contrast, the effect of lidocaine in the normal animals was negligible. It is concluded that lidocaine significantly depresses His-Purkinje conduction in the setting of preexisting ischemic damage. These results suggest that lidocaine may be used as a diagnostic tool to unmask latent His-Purkinje conduction defects due to ischemia.     

Effect of sudden rate acceleration on the human His-Purkinje system: adaptation of refractoriness in a dampened oscillatory pattern

Although the refractoriness of the human His-Purkinje system (HPS) during constant-cycle length pacing appears to be closely related to the cycle length of the stimulation, the mode of adaptation of this refractoriness with sudden rate acceleration is not well understood. A systematic evaluation of this adaptation was performed in 14 patients with normal QRS durations and HV intervals referred for electrophysiologic evaluation. The relative refractory period of the HPS (HPS-RRP) was evaluated by the extrastimulus (S2) method during a constant ventricular drive (S1) having a cycle length as close to sinus rhythm as possible. An accelerated train of 6 ventricular beats (S1') was then added to the constant drive and the HPS-RRP of each successive beat of this train was similarly determined. Mean S1 cycle length was 750 +/- 164 msec (range 600 to 1000). Mean S1' cycle length was 475 +/- 55 msec (range 400 to 600). The HPS-RRP of each successive beat of the accelerated train was significantly shorter than that during the S1 drive and behaved in a dampened oscillatory fashion alternating from a lower value on the odd-numbered beats to a higher value on the even-numbered beats. In contrast, the effective and relative refractory periods of the ventricular myocardium during the accelerated train behaved in a cumulative manner, decreasing progressively with the first 2 beats of the train before reaching a plateau value. In conclusion, the data reported here present a new and intriguing picture of the mode of adaptation of the HPS refractoriness to sudden rate acceleration. At least in the range of the cycle lengths used in this study, the refractoriness of the HPS behaves in a dampened oscillatory manner that is radically different from the behavior of the ventricular myocardial refractoriness.     

Postextrasystolic alterations in refractoriness of the His-Purkinje system and ventricular myocardium in man

The changes in refractoriness of the His-Purkinje system (HPS) and ventricular myocardium (VM) that are associated with the occurrence of postextrasystolic beats in man are unknown. Accordingly, using a pacing model of the cycle length changes created by a ventricular extrasystole-postextrasystole sequence, we measured retrograde HPS and VM relative and effective refractory periods (RRP and ERP) in 15 patients with the use of ventricular test extrastimuli during preextrasystolic basic control drive (method I) and after programmed extrasystolic (method II) and postextrasystolic (method III) beats. The basic cycle length (same for all three methods) ranged from 500 to 700 msec (mean 613 +/- 74 msec) and the extrasystolic coupling interval (identical for methods II and III) comprised 68 +/- 4% of the basic cycle length. In method III the postextrasystolic pause was programmed to equal the basic cycle length (i.e., noncompensatory) so that method I could serve as control for method III. RRP-HPS decreased from 331 +/- 37 msec in method I to 245 +/- 37 msec or less during the extrasystolic beat (p less than .001). A less dramatic corresponding shortening of ERP-VM and RRP-VM was observed, i.e., from 245 +/- 21 and 264 +/- 23 msec (method I) to 233 +/- 23 and 251 +/- 22 msec (method II), respectively (p less than .001). With the postextrasystolic beat, however, RRP-HPS increased to exceed the control value of method I by 23 +/- 11 msec (p less than .001). This greater-than-expected RP prolongation was also associated with significantly increased retrograde HPS conduction times (in method III vs method I) at both long and short test stimulus coupling intervals.(ABSTRACT TRUNCATED AT 250 WORDS)     

运用希浦传导系统解剖指导传导束起搏定位

近年来,希浦传导系统起搏已成为在心力衰竭需要心室起搏的患者中替代传统右心室起搏的一种可行方法.在术中,术者需要将电极精确定位在希氏束或左束支区域,而能否成功植入起搏电极,很大程度上取决于术者对希浦传导系统解剖分布特点及其心脏结构变异的了解.本文旨在分析房室结区、希氏束及左束支近端的解剖特点,以及传导系统不同解剖结构与传导系统病变发生的关系,为指导希浦传导系统起搏提供参考.     

Acute effects of amiodarone on membrane properties,refractoriness, and conduction in guinea pig papillary muscles

Summary Amiodarone has potent and complex antiarrhythmic effects associated with a rare incidence of proarrhythmia. For a comprehensive understanding of its antiarrhythmic mechanisms in the same preparations, amiodarone (50 µM) was employed as it would be in the clinical setting and applied to guinea pig papillary muscles impaled by microelectrodes, paced at different rates, and superfused with various concentrations of potassium ([K]_e). Amiodarone exerted complex actions, as follows: (1) The maximum rate of rise (V_max) of the fast action potential (i.e., [K]_e = 5.4–9.0mM) as well as that of the slow action potential (i.e., [K]_e = 15.0mM in the presence of 1.0µM isoproterenol) was suppressed in a rate-dependent manner. (2) Amiodarone exhibited a rate- and [K]_e-dependent increase in the ratio of effective refractory period vs action potential duration at 90% repolarization (ERP/APD₉₀), disclosing post-repolarization refractoriness. (3) Amiodarone had no effect on passive cable factors, such as threshold current and tissue resistance, during propagation. These versatile electrophysiological effects of amiodarone may contribute to its unique antiarrhythmic effects, as well as the low incidence of proarrhythmia with this drug.     

Effects of intravenous amiodarone on ventricular refractoriness, intraventricular conduction, and ventricular tachycardia induction.

AIMS: Intravenous amiodarone has recently emerged as an important drug for the acute treatment of ventricular tachyarrhythmias. However, electrophysiological actions and the efficacy of the drug in the suppression of ventricular tachycardia inducibility have not yet been fully established. The present study was designed to address these issues. METHODS AND RESULTS: The study group consisted of 18 patients (all males, mean age 75 +/- 14 years), who underwent electrophysiological study due to a history of sustained ventricular tachyarrhythmia or syncope with non-sustained ventricular tachycardia detected on ambulatory ECG monitoring. The effects of 5 mg.kg(-1) or 10 mg.kg(-1) of intravenous amiodarone on (1) ventricular refractoriness (QTc interval, right ventricular effective refractory period and monophasic action potential duration), (2) intraventricular conduction (paced-QRS and signal-averaged QRS duration), and (3) ventricular tachycardia inducibility, were examined. The drug had no significant effect on ventricular refractoriness. However, a relatively small but significant slowing of intraventricular conduction was seen (paced-QRS duration: 182 +/- 27 ms vs 191 +/- 28 ms, P<0.0007; 183 +/- 32 ms vs 195 +/- 33 ms, P<0.0007; and 177 +/- 21 ms vs 192 +/- 24 ms, P<0.003, at the cycle lengths of 600, 500 and 400 ms, respectively). This effect was more evident during extrasystolic beats than during stable pacing (for example, at the cycle length of 600 ms, the magnitude of amiodarone-induced lengthening of QRS duration was 23.9 +/- 17.6 ms vs 9.7 +/- 7.2 ms, P<0.009, respectively). Intravenous amiodarone did not prevent induction of sustained ventricular tachycardia in any of five patients inducible at baseline. Of six patients with non-sustained ventricular tachycardia, five had sustained ventricular tachycardia or fibrillation induced after amiodarone infusion. CONCLUSION: Intravenous amiodarone does not prolong ventricular refractoriness, slows intraventricular conduction and may facilitate inducibility of sustained ventricular arrhythmias.     

Divergence between refractoriness of His-Purkinje system and ventricular muscle with abrupt changes in cycle length

The concept that refractoriness of the His-Purkinje system (HPS) and ventricular muscle both vary directly with cycle length is based on observations during the use of constant cycle length. During abrupt changes in ventricular cycle length, refractoriness of the ventricular muscle is known to reflect the cumulative durations of preceding cycle lengths. The effect of such changes on retrograde refractoriness of the HPS is not known. In this study refractoriness of ventricular muscle and of the HPS was evaluated in 30 patients with normal intraventricular conduction by the ventricular extrastimulus (V2) technique during constant cycle length (method I) and during abrupt cycle length changes (method II). During method II the cycle length immediately before V2 was identical to the constant cycle length of method I and therefore was designated as the reference cycle length (CLR); however, the cycle length preceding (CLP) CLR was either longer than CLR (method IIA) by 100 to 300 msec in 11 patients or shorter than CLR (method IIB) by 100 to 300 msec in 30 patients. Results showed that compared with method I, method IIA shortened the relative refractory period (RRP) of the HPS from 350 +/- 29 to 344 +/- 29 msec (p less than .04), whereas the effective refractory period (ERP) of the ventricular muscle increased from 225 +/- 21 to 233 +/- 20 msec (p less than .0001). In contrast, compared with method I, method IIB lengthened the RRP of the HPS from 335 +/- 30 to 351 +/- 35 msec (p less than .0001), whereas ERP of the ventricular muscle decreased from 223 +/- 23 to 213 +/- 22 msec (p less than .0001). Similar to the inverse relationship between CLP and RRP of the HPS, ERP of the HPS was prolonged with short CLP (method IIB) compared with long CLP (method IIA). The results indicate a marked divergence between refractoriness of the HPS and of ventricular muscle during abrupt cycle length changes; these results were not previously anticipated. Whereas ventricular muscle responded to cumulative effects of preceding cycle lengths and varied directly with CLP, the HPS appeared to respond to directional and/or dynamic changes in cycle length and varied inversely with CLP. Moreover, in contrast to ventricular muscle, the HPS appeared to be responsive to rate of change in cycle length whereby short-to-long change in cycle length had a greater effect than long-to-short change in cycle length.     

Effect of autonomic nervous system modulation on retrograde atrioventricular nodal conduction in the human heart

Although the influence of the autonomic nervous system on anterograde atrioventricular nodal conduction is well established, its effect on retrograde atrioventricular nodal conduction has not been examined systematically. Since retrograde atrioventricular nodal conduction in subjects with normal anterograde conduction may vary from intact retrograde conduction to complete retrograde block when assessed during ventricular pacing, in this study patients with (a) intact retrograde atrioventricular nodal conduction (group 1) were studied during parasympathetic (vagal) stimulation by carotid sinus pressure and during sympathetic inhibition (propranolol 0.2 mg.kg-1 intravenously) and (b) retrograde atrioventricular nodal block (group 2) were studied during vagal blockade (atropine 0.04 mg.kg-1 intravenously) and during sympathetic stimulation (isoproterenol 1-4 micrograms.min-1 infusion). In both groups changes in sinus cycle length and anterograde atrioventricular nodal conduction were measured. In group 1 vagal stimulation by carotid sinus pressure in 20 patients caused the cycle length at which retrograde atrioventricular nodal block was induced to be significantly lengthened from a mean(SD) of 375(59) to 451(51) ms in six patients; caused complete retrograde block in 10 patients; and had no effect in four patients. Sympathetic inhibition by propranolol in another 15 patients delayed the onset of pacing induced retrograde atrioventricular nodal block from a mean(SD) of 340(60) to 418(80) ms in 11 patients; caused complete retrograde atrioventricular nodal block in three patients; and had no effect in one patient. In group 2 vagal blockade by atropine caused a 1:1 retrograde response during ventricular pacing up to a mean(SD) cycle length of 470(135) ms in six out of eight patients. The infusion of isoproterenol caused the retrograde atrioventricular nodal block to be abolished and 1:1 conduction to be resumed up to a ventricular pacing mean(SD) cycle length of 364(57) ms in six out of eight patients. It is concluded that (a) the autonomic nervous system modulates retrograde atrioventricular nodal conduction in a similar manner to its anterograde counterpart and (b) that since retrograde atrioventricular nodal conduction was reversible after the administration of either atropine or isoproterenol retrograde atrioventricular nodal block may be dynamic (physiological) rather than fixed (anatomical) in nature.     

Effects of digitalis on ventricular myocardial and His-Purkinje refractoriness and reentry in man

The effects of digitalis on retrograde conduction and refractoriness of the His-Purkinje system, ventricular myocardium and reentry within the His-Purkinje system were studied in 17 patients using the ventricular extrastimulus (V₂) technique. Studies were performed, before and 30 minutes after intravenous administration of ouabain, 0.01 mg/kg. After treatment with ouabain, there was a significant decrease in the functional refractory period (266 ± 19 to 254 ± 18 msec, P < 0.001), relative refractory period (253 ± 17 to 240 ± 16 msec, P < 0.001) and effective refractory period (242 ± 23 to 231 ± 24 msec, P < 0.005) of the ventricular muscle. In contrast, there was no significant change in retrograde His-Purkinje conduction and refractoriness. The phenomenon of reentry within the His-Purkinje system characterized by the reentrant beat (V₃) at critical retrograde conduction delays in the His-Purkinje system (V₂-H₂) within a narrow range of V₁–V₂ intervals was seen in 10 of 17 patients. Ouabain increased and shifted to the left the zone of reentry within the His-Purkinje system in 7 of 10 patients (36 ± 23 to 55 ± 23 msec, P < 0.001) and decreased it by 10 to 30 msec in the remaining 3 patients. The critical V₂-H₂ (186 ± 29 to 193 ± 27 msec, difference not significant [NS]) and V₁–V₂ (299 ± 30 to 294 ± 36 msec, NS) intervals for reentry did not significantly change after ouabain. However, the minimal V₁–V₂ intervals (266 ± 26 to 253 ± 25 msec, P < 0.025) decreased significantly, whereas the maximal V₂-H₂ intervals (266 ± 40 to 239 ± 37 msec, P < 0.01) increased significantly.

Thus, in the intact human heart, digitalis (1) significantly decreased all measures of ventricular myocardial refractoriness, (2) had no significant effect on retrograde conduction and refractoriness of the His-Purkinje system, and (3) widened the zone of reentry within the His-Purkinje system due to shortening of the functional refractory period of the ventricular muscle with attainment of longer V₂-H₂ delays.     

The effect of heart rate, acetylcholine, and vagal stimulation on antegrade and retograde His-Purkinje conduction in the intact heart

In ten dogs the effects of acetylcholine, graded vagal stimulation, and heart rate on both antegrade and retrograde His-Purkinje conduction were evaluated. His bundle pacing was used to obtain the antegrade His-Purkinje conduction time and pacing the ventricle and recording the retrograde His bundle electrogram gave the retrograde His-Purkinje conduction time. Acetylcholine and vagal stimulation sufficient to produce cardiac arrest had no effect on antegrade and retrograde His-Purkinje conduction. Similarly, pacing at cycle lenghts varying from 400 to 200 msec. had no effect on antegrade or retrograde conduction time. However, when the cycle length of ventricular pacing was decreased to less than 200 msec. various degrees of retrograde His-Purkinje conduction delay and block developed.     

Progressive improvement of His-Purkinje conduction during recovery from catheter-induced heart block.

Complete heart block developed during HBE studies in a patient with left bundle branch block, after inadvertent catheter-induced trauma to the right bundle branch. Normal intraventricular conduction (HV interval) was documented during the initial part of the study, and was demonstrated to be markedly prolonged after the appearance of heart block. Conduction through the right bundle branch improved over a short period of time as manifested by steplike shortenings of the HV interval, until the original conduction velocity was re-established. This case strongly supports the concept that the His-Purkinje system is capable of varying its conduction velocity and further demonstrates that, in patients with bundle branch block, a prolonged HV interval indicates disease of the remaining bundle branch.     

Effect of glucose-insulin-potassium infusion on the human conduction system

His bundle electrograms were performed in 21 patients with organic heart disease. Recordings were made at various rates utilizing right atrial pacing. A mixture containing 50 g of glucose, 10 mEq of potassium and 20 units of insulin was given intravenously over 10 minutes to 10 subjects. The P-A, A-H, H-Q and H-S intervals were determined before and immediately after the glucose-insulin-potassium infusion. A significant prolongation in the A-H interval occurred with negligible effects on the P-A, H-Q and H-S intervals. At the atrial pacing rate of 100/min, the average A-H interval increased from the control value of 140 msec to 151 msec after the infusion (P < 0.05); at the pacing rate of 140/min, the A-H interval increased from 145 to 165 msec (P < 0.05). The identical study was performed in three additional patients who received an infusion of 50 g of glucose and 20 units of insulin. No significant change was observed in the conduction system. In eight patients a solution of 2.6 mEq of potassium in 65 cc of 5 percent glucose and water was infused over an 8 minute period. A significant prolongation of the A-H interval was observed. At the atrial pacing rate of 100/min, the average A-H interval increased from the control value of 122 to 133 msec after the glucose and potassium infusion (P < 0.05), whereas at the pacing rate of 140/min, the A-H interval increased from 165 to 188 msec (P < 0.05). These findings demonstrate that the potassium in a glucose-potassium-insulin infusion may cause impaired conduction through the atrioventricular node.     

Effect of procainamide on reentry within the His-Purkinje system in man

The effects of a single intravenous infusion of 500 mg of procainamide on macro-reentry within the His-Purkinje system were assessed, in 10 patients using bundle of His electrograms and the ventricular extrastimulus method. Procainamide did not abolish reentry in any of the 10 patients and produced repetitive reentry (two or more consecutive reentrant beats) in 8 of 10 patients. On the average, procainamide caused reentry to be initiated at longer S₁-S₂ intervals, widening the zone of reentry. In all but one patient reentry was manifest at significantly longer S₂-H₂ intervals than control values. The H-V intervals of reentrant beats (H₂-V₃ intervals) after procainamide were longer than control values at comparable S₂-H₂ intervals. Procainamide shortened or abolished the retrograde gap zones thereby causing reentry to be present more frequently within the zone of reentry. No significant change was seen in effective refractory period of ventricular muscle.

On the assumption that many clinically encountered ventricular arrhythmias that respond to procainamide result from micro-reentry, the observed differences between the effects of procainamide on macro- and micro-reentry may be explained on the basis of the relation between drug effect and size of the reentrant circuit. Procainamide may produce a greater increase in refractoriness in a micro-reentrant circuit than in macro-reentry, thereby producing bilateral block and abolishing reentry in the former; or if the degree of electrophysiologic changes produced by procainamide were the same in both types of circuits, then for a given change, the pathway in a micro-reentrant circuit may be too small to sustain reentry.