Intracardiac Stimulation of Human Parasympathetic Nerve Fibers Induces Negative Dromotropic Effects:

Intracardiac Stimulation and Dromotropic Effect. Introduction : The dromotropic effects of intracardiac parasympathetic nerve stimulation have not been well studied; furthermore, the effects of radiofrequency ablation lesions on parasympathetic nerve stimulation are not clear.
Methods and Results : Group I: intracardiac electrical stimulation in the right posteroseptal and anteroseptal areas under different stimulation strengths; group II: intracardiac electrical stimulation before and 10 minutes after intravenous propranolol; group III; intracardiac electrical stimulation before and 5 minutes after intravenous atropine. Among the 10 patients with AV nodal reentrant tachycardia (group IV) and the 10 patients with atrial flutter (group V), atrial fibrillation was induced before and after successful ablation, and intracardiac electrical stimulation in the right posteroseptal area was performed before and after successful ablation. The maximal response and complete decay of the response occurred within 2 to 6 seconds of initiation or termination of parasympathetic nerve stimulation. This negative dromotropic effect disappeared after atropine was administered, but not after propranolol. After successful ablation, parasympathetic stimulation still induced negative dromotropic effects.
Conclusion : Electrical stimulation of parasympathetic nerve fibers near the posteroseptal and anteroseptal areas could induce a negative dromotropic effect, and this effect was preserved after successful radiofrequency ablation of slow pathway and isthmus conduction.     

Characterization of Sinoatrial Parasympathetic Innervation in Humans

INTRODUCTION: The response to sinoatrial parasympathetic nerve stimulation (shortened atrial refractoriness) was used to determine the atrial distribution of these nerve fibers in humans. We hypothesized that, in humans, parasympathetic nerves that innervate the sinoatrial node also innervate the right atrium and that the greatest density of innervation is near the sinoatrial nodal fat pad. METHODS AND RESULTS: Temporary epicardial wire electrodes were sutured in pairs in the sinoatrial nodal fat pad, high right atrium, and right ventricle by direct visualization during coronary artery bypass surgery in nine patients. Appropriate electrode placement was confirmed by electrically stimulating the fat pad in the operating room to prolong sinus cycle length by 50%. Experiments were performed in the electrophysiology laboratory 1 to 5 days after surgery. Programmed atrial stimulation was performed via an endocardial electrode catheter advanced to the right atrium. The catheter tip electrode was moved in 1-cm concentric zones around the epicardial wires by fluoroscopic guidance. Atrial refractoriness was determined in the presence and absence of sinoatrial parasympathetic nerve stimulation at each catheter site. In 8 of 9 patients, parasympathetic nerve stimulation reproducibly prolonged sinus cycle length by 50%. There was no effect on AV nodal conduction (no prolongation of PR interval) and no change in AV nodal refractoriness. Atrial effective refractory periods reproducibly shortened in response to parasympathetic nerve stimulation in 1-cm zones up to 3 cm surrounding the fat pad, by a mean (+/- SEM) of 26.6+/-4.3 msec (zone 1), 11.4+/-1.8 msec (zone 2), and 10.0+/-2.5 msec (zone 3), respectively (P = 0.0001). At distances > 3 cm from the fat pad, the effective refractory period did not shorten. CONCLUSION: Stimulation of parasympathetic nerves that innervate the sinoatrial node shortened atrial refractoriness in humans.     

Identification and characterization of atrioventricular parasympathetic innervation in humans

INTRODUCTION: We hypothesized that in humans there is an epicardial fat pad from which parasympathetic ganglia supply the AV node. We also hypothesized that the parasympathetic nerves innervating the AV node also innervate the right atrium, and the greatest density of innervation is near the AV nodal fat pad. METHODS AND RESULTS: An epicardial fat pad near the junction of the left atrium and right inferior pulmonary vein was identified during cardiac surgery in seven patients. A ring electrode was used to stimulate this fat pad intraoperatively during sinus rhythm to produce transient complete heart block. Subsequently, temporary epicardial wire electrodes were sutured in pairs on this epicardial fat pad, the high right atrium, and the right ventricle by direct visualization during coronary artery bypass surgery in seven patients. Experiments were performed in the electrophysiology laboratory 1 to 5 days after surgery. Programmed atrial stimulation was performed via an endocardial electrode catheter advanced to the right atrium. The catheter tip electrode was moved in 1-cm concentric zones around the epicardial wires by fluoroscopic guidance. Atrial refractoriness at each catheter site was determined in the presence and absence of parasympathetic nerve stimulation (via the epicardial wires). In all seven patients, an AV nodal fat pad was identified. Fat pad stimulation during and after surgery caused complete heart block but no change in sinus rate. Fat pad stimulation decreased the right atrial effective refractory period at 1 cm (280 +/- 42 msec to 242 +/- 39 msec) and 2 cm (235 +/- 21 msec to 201 +/- 11 msec) from the fat pad (P = 0.04, compared with baseline). No significant change in atrial refractoriness occurred at distances >2 cm. The response to stimulation decreased as the distance from the fat pad increased. CONCLUSION: For the first time in humans, an epicardial fat pad was identified from which parasympathetic nerve fibers selectively innervate the AV node but not the sinoatrial node. Nerves in this fat pad also innervate the surrounding right atrium.     

Prevention of Short Term Reversible Chronic Atrial Fibrillation by Permanent Pacing at the Triangle of Koch

Objectives: The purpose of this study was to investigate if single lead interatrial septum pacing could be effective in maintaining sinus rhythm in patients in whom restoration of sinus rhythm was only possible for a period of 2–24 hours after one or more previous electrical cardioversions, and in whom a sinus bradycardia was documented before arrhythmia restarted. The two hours limit was chosen because it was considered a sufficient time to implant a dual chamber pacemaker. Background: Alternative atrial pacing techniques have been demonstrated to be successful in preventing recurrences of atrial fibrillation (AF) in patients with sinus bradycardia. Excluding the AF occurring after only a few sinus beats, at 24 hours from electrical cardioversion an early restart of chronic AF has been reported in 12[emsp4 ]% to 17[emsp4 ]% of the patients. Methods: After sinus rhythm was restored by internal electrical cardioversion, 17 patients, 7 ablated at the AV junction, underwent a dual chamber rate response (DDDR) pacemaker implantation with a screw-in atrial lead placed in the interatrial septum. Results: After a follow-up period of 17±5 months (range 12 to 27 months) persistence of sinus rhythm was observed in 11 patients (65[emsp4 ]%). Six patients (35[emsp4 ]%) had recurrences of paroxysmal attacks, while five (30[emsp4 ]%) were totally free of AF. Recurrence of chronic AF was observed in six cases (35[emsp4 ]%) after 2 days–12 months from implantation. No dislodgements of the atrial lead and no complications were observed at implantation and during follow-up. Conclusions: Interatrial septum pacing is a safe and feasible technique with a satisfying success rate (65[emsp4 ]%) in long-term maintaining sinus rhythm in previously unsuccessfully cardioverted patients.     

Cardiac Swelling Associated with Linear Radiofrequency Ablation in the Atrium

Objectives: To characterize myocardial swelling in response to application of endocardial radio- frequency ablation lesions. Background: In individual patients, we have observed that ablation in the posterior right atrium was associated with echocardiographic evidence of atrial and contiguous right pulmonary vein wall swelling. Methods: 1. Human Subjects: linear ablation was performed in the posterior right atrium in 10 subjects; a portion of the ablation lesion was contiguous to the right pulmonary vein; this area was defined as the contiguity zone. In the contiguity zone, right atrial wall thickness and pulmonary vein lumen diameter were measured utilizing intracardiac echocardiography. Measurements were made just prior to (baseline) and immediately after ablation.2. Porcine Subjects: linear ablation was performed in the posterior right atrium of 14 pigs. In the contiguity zone, atrial wall thickness, interstitial space thickness, right pulmonary vein wall thickness and lumen diameter were measured using intracardiac echocardiography. Measurements were made at baseline, immediately after ablation, and at 1, 4, 8 or 12 weeks after ablation (followup). Post-mortem pathologic evaluation of the contiguity zone was performed. Results: 1. Human Subjects: Immediately after ablation, relative to baseline right atrial wall thickness was significantly increased (9.4±3.1[emsp4 ]mm versus 5.4±1.5[emsp4 ]mm) and right pulmonary vein lumen diameter was significantly decreased (6.2±2.9[emsp4 ]mm versus 8.1±2.9[emsp4 ]mm).2. Porcine Subjects: Immediately after ablation, right atrial wall thickness (4.1±1.2[emsp4 ]mm), interstitial space thickness (1.9±1.1[emsp4 ]mm), and right pulmonary vein wall thickness (1.2±0.4[emsp4 ]mm) were each significantly increased relative to baseline (1.0±0.3[emsp4 ]mm, 0±0[emsp4 ]mm, and 0.7±0.2[emsp4 ]mm, respectively) and pulmonary vein lumen diameter was significantly decreased (5.0±1.4[emsp4 ]mm versus 6.9±2.2[emsp4 ]mm). Similar findings were made at the 1 week followup interval. At 4, 8 and 12 week followup intervals, thicknesses and lumen diameter were not significantly different from baseline. At post-mortem examination, direct measurements of wall thickness were significantly correlated with echocardiographic measurements. Histologic analysis demonstrated edema to be the cause of the early wall thickness and lumen diameter changes. Ablation lesions were transmural in the right atria of all animals; in some animals, lesion formation was also observed in the pulmonary vein wall. Conclusions: Cardiac edema resulting from right atrial linear ablation results in swelling of atrial and contiguous right pulmonary vein walls, as well as the interposed extracardiac interstitial space. These changes are associated with a decrease in pulmonary vein lumen diameter. Swelling evolves rapidly and resolves within 4 weeks.     

Selective stimulation of parasympathetic nerve fibers to the human sinoatrial node.

BACKGROUND. In animals, parasympathetic nerve fibers that innervate the sinoatrial node can be selectively stimulated to increase atrial cycle length. These nerve fibers course through an epicardial fat pad at the margin of the right superior pulmonary vein, the superior vena cava, and the right atrium. We hypothesized that similar nerves exist and can be selectively stimulated in humans. METHODS AND RESULTS. Microscopic examination of fat pads excised from the margin of the right superior pulmonary vein, the superior vena cava, and the right atrium during two human autopsies revealed the presence of nerve fibers and ganglia. We electrically stimulated this epicardial fat pad in 16 patients during cardiac surgery. The fat pads were stimulated with continuous-pulse trains for 15 seconds via a hand-held bipolar electrode using constant current (10-15 mA), constant pulse width (0.02-0.05 msec), and at 6.6, 10, 20, 25, and 30 Hz. The mean atrial cycle length +/- 1 SEM increased from 734 +/- 34 msec at baseline to a maximum of 823 +/- 61 msec at 6.6 Hz, 1,167 +/- 125 msec at 10 Hz, 1,734 +/- 281 msec at 20 Hz, 2,993 +/- 661 msec at 25 Hz, and 2,461 +/- 668 msec at 30 Hz during nerve stimulation. Linear regression analysis showed that the response of atrial cycle length to sinoatrial parasympathetic nerve stimulation was frequency dependent. The maximum response and complete decay of the response occurred within 4-8 seconds of initiation or termination of sinoatrial parasympathetic nerve stimulation. Atrioventricular conduction time and the PR interval did not change during sinoatrial parasympathetic nerve stimulation, even when the atria were paced at the baseline heart rate. CONCLUSIONS. Electrical stimulation of parasympathetic nerve fibers in a fat pad near the sinoatrial node increased atrial cycle length without affecting atrioventricular nodal conduction. This is the first study in which such nerve fibers that innervate the sinoatrial node have been selectively stimulated in humans.     

Vagal efferent control of electrical properties of the heart in experimental diabetes

Autonomic neuropathy is a common and severe complication of diabetes mellitus that leads to dysfunction of the cardiovascular system. The reduced ability to finely regulate heart rate is attributed to an impairment of cardiac parasympathetic regulation, but it is not known whether this is due to parasympathetic neuropathy and/or direct cardiac impairments. Therefore, we recorded the electrocardiogram of streptozotocin-induced diabetic rats under basal conditions and during electrical stimulation of the vagus nerve. We used the neurotrophic agent Org 2766, an adrenocorticotropic hormone [ACTH]-(4–9) analogue, to investigate the involvement of a neurogenic component in the altered vagal control of heart rate. The R-R interval was increased and atrioventricular transmission time unchanged 1 week after diabetes induction and remained so until 20 weeks. Treatment with Org 2766 could not prevent the bradycardia. After bilateral vagotomy, both diabetic and non-diabetic rats had the same R-R and P-R interval. The response of the R-R interval to electrical stimulation of the right vagus nerve was impaired, and this impairment was not reversed by Org 2766 in diabetic rats. These results suggest that neurogenic factors are of little or no importance in the impaired parasympathetic control of heart rate seen in experimental diabetes. Received: 6 June 1997 / Accepted in revised form: 27 November 1997     

The Hemostatic Effects of Warfarin Titration in Post CABG Patients in Comparison to Placebo Treatment

Background: Since coronary artery bypass graft patients remain at risk of coronary artery and bypass graft occlusion after successful surgery, adjunct treatment regimens are under investigation. In a study of the patients of the multicenter Post Coronary Artery Bypass Graft (Post CABG) Trial, 1[emsp4 ]mg warfarin was found to have no important effect on coagulation parameters. Study design: The effects of 1, 2 and 3[emsp4 ]mg warfarin were evaluated at six-week intervals in 20 Post CABG Trial patients receiving titrated dose increases in comparison to 20 patients of similar age, gender and time from CABG treated with placebo. Results: International normalized ratio (INR) values increased with warfarin dose increments for 1, 2, and 3[emsp4 ]mg, respectively (0.95±0.16, 1.08±0.19, and 1.34±0.39) and in comparison to placebo treated patients (dose×treatment p<0.001). Factor VII coagulant activity decreased with warfarin titration (1[emsp4 ]mg, 119.0±18.3%%; 2[emsp4 ]mg, 100.6±32.8%%; 3[emsp4 ]mg, 95.0±27.8%%) and in comparison to placebo (dose×treatment p=0.008). Levels of prothrombin fragment F1.2, tissue plasminogen activator, fibrinogen and von Willebrand factor were unchanged with warfarin dose increments and in comparison to placebo. Conclusions: At doses up to 3[emsp4 ]mg, warfarin acts on the INR through a reduction of factor VII with no effect on the fibrinolytic system, fibrinogen or von Willebrand factor. At these doses F1.2 did not document reduced coagulation activity. The observations of this study were consistent with the decision in the Post CABG Trial to increase the warfarin dose above 1[emsp4 ]mg to achieve a distinct effect of warfarin that was less than full anticoagulation.     

Pacemaker Repetitive Nonreentrant Ventriculoatrial Synchronous Rhythm. A Review

The normal functioning of dual chamber pacemaker-cardioverter defibrillator (AV pacer/ICD) may be affected by oversensing of the farfield R wave (FFRW) by the atrial channel. This study aimed to investigate whether placement of the AV pacer/ICD's atrial lead at a lateral (LAT) wall location compared to a medial (MED) location i.e. the appendage of the right atrium, would reduce the amplitude of FFRWs but not the nearfield atrial electrograms (AEGMs) during sinus rhythm (SR) and ventricular fibrillation (VF). In 17 patients, real time electrograms were recorded during SR and induced VF through the atrial lead initially at the MED and subsequently at the LAT location. In 10 patients the electrograms in SR were also recorded on a computerized data acquisition and recording system at different band-pass filter settings. Although FFRWs were recorded both at MED and LAT locations, they were much smaller, 3.5±4.1[emsp4 ]mm during SR and 1.7±2.2[emsp4 ]mm during VF at the LAT location. At 30–500[emsp4 ]Hz band-pass filter, lower amplitudes of FFRWs 0.14±0.09[emsp4 ]mV were recorded at the LAT location. The V/A ratios of the amplitudes of FFRWs and AEGMs were smaller at the LAT location during SR and VF. The nearfield AEGMs were of similar amplitudes at the MED and LAT locations. These data indicate that lower amplitudes of FFRWs are recorded by placement of the atrial lead at the lateral wall of the right atrium. Oversensing of FFRWs may be prevented to improve functioning of the AV pacer-ICD.     

自主神经系统在心律失常中的调控作用

目的探讨迷走神经与交感神经在心律失常中的介导作用。方法以最长R R间期>1.5s各类心律失常患者为研究对象,应用24h动态心电图测定病人的心率变异性(HRV)的变化趋势。结果①与对照组比较期前收缩组HRV无明显差异。窦性心动过缓、窦房传导阻滞组病人的HRV指标上升,主要以迷走神经张力增高为主,而窦性停搏组随R-R间期延长HRV指标反而明显下降有非常显著性差异(P<0.01)。②期前收缩组内各型心律失常HRV指标无统计学意义,P>0.05。窦性心动过缓、窦房传导阻滞组不同最长R R间期组HRV指标无统计学意义,P>0.05。结论结果提示窦房结功能不良的患者HRV降低,其降低的程度与窦房结病变的严重程度呈正相关。     

Paradoxical Change in Atrial Fibrillation Dominant Frequencies with Baroreflex‐Mediated Parasympathetic Stimulation with Phenylephrine Infusion

Baroreflex Response and AF Dominant Frequency . Introduction: Parasympathetic stimulation is known to promote atrial fibrillation (AF) through shortening of atrial refractory periods. We hypothesized that baroreflex‐mediated parasympathetic stimulation via phenylephrine (PE) infusion would increase AF rate as measured by dominant frequency (DF). Methods and Results: The protocol was performed in 27 patients (24 M, 59 ± 1 years old) prior to AF ablation. For 10 patients in AF, PE was infused until systolic blood pressure increased ≥30 mmHg. Electrograms were recorded in the left atrium before and after PE. DFs of each recording were calculated offline. Atrial effective refractory periods (ERPs) were measured before and after PE in 11 patients who were in sinus rhythm during the procedure. DFs were also measured in 6 patients in AF before and after complete parasympathetic blockade with atropine (0.04 mg/kg). PE resulted in increased RR intervals during sinus rhythm (1,170 ± 77 to 1,282 ± 85 ms, P = 0.03) and AF (743 ± 32 to 826 ± 30 ms, P = 0.03), consistent with parasympathetic effect on the sinus and AV nodes, respectively. DFs were decreased by PE in the left atrium (6.2 ± 0.2 to 6.0 ± 0.2 Hz, P = 0.004). Correspondingly, atrial ERPs significantly increased from 218 ± 13 to 232 ± 11 ms (P = 0.04). Atropine resulted in a decreasing trend in DF in the left atrium (5.9 ± 0.1 to 5.8 ± 0.1 Hz, P = 0.07). Conclusions: Despite baroreflex‐mediated parasympathetic effect, PE produced a slowing of AF along with lengthening of ERP, while parasympathetic blockade also slowed DF. It is therefore likely that the direct and indirect adrenergic effects of PE on atrial electrophysiology are more prominent than its parasympathetic effects. (J Cardiovasc Electrophysiol, Vol. 23 pp. 1045‐1050, October 2012)     

Effects of Sodium Channel Blockade on Ibutilide Induced Prolongation of Repolarization in the Isolated Rabbit Ventricle

Introduction: Ibutilide fumarate is indicated for the termination of atrial fibrillation and atrial flutter. It's mechanism of action is unclear but may involve activation of a late inward Na⁺ current. Methods and Results: Twenty seven experiments were performed using an isolated perfused rabbit right ventricle preparation. In each experiment effective refractory periods (ERP) and transmembrane 90% action potential durations (APD) were measured. In 8 experiments ERP and APD were measured at baseline, in the presence of ibutilide (0.1[emsp4 ]uM), and in the presence of both ibutilide and tetrodotoxin (TTX, 2[emsp4 ]uM). In 8 experiments lidocaine (10[emsp4 ]uM) was used in place of TTX. Measures were made at 200, 400, and 800[emsp4 ]msec paced cycle lengths under each condition. The baseline values for APD at 200, 400 and 800[emsp4 ]msec cycle lengths for the experiments treated with ibutilide and TTX were 111±8, 140±14 and 159±22[emsp4 ]msec, respectively. In the presence of ibutilide, APD increased to 130±19, 192±26 and 217±35[emsp4 ]msec at 200, 400 and 800[emsp4 ]msec cycle lengths, respectively (all p0.03). After the addition of TTX there was no shortening of APD or ERP compared to treatment with ibutilide alone at any cycle length (all p0.062). Similarly, in the presence of ibutilide and lidocaine there were no changes in APD or ERP compared to treatment with ibutilide alone (all p0.41). In 11 control experiments, there were no changes in APD or ERP on serial measures after placebo and TTX or lidocaine. Conclusion: Ibutilide induced prolongation of ventricular repolarization is not affected by Na⁺ channel blockade with lidocaine or TTX in the isolated rabbit heart. These findings suggest that the effects of ibutilide are not mediated by a Na⁺ channel dependent late current or that this mechanism contributes minimally to its action in this model.     

Identification of preferential sites of parasympathetic input to the atrioventricular node in man.

OBJECTIVES: The effects of subthreshold stimulation performed at various sites in the perinodal and posteroseptal space on atrioventricular (AV) nodal conduction were investigated. BACKGROUND: The identification of specific or preferential sites of parasympathetic innervation to the AV node is suggested by observations made in both the animal and clinical laboratories. Pathologic studies of the parasympathetic innervation to the AV node show it is made up of serpiginous fibers traveling at highly specific sites within the myocardium endocardially towards the compact AV node. METHODS: We utilized endocardial subthreshold stimulation to selectively identify and characterize AV nodal inputs. Fourteen patients (age: 56 +/- 4 years) undergoing electrophysiologic testing with or without radiofrequency ablation for supraventricular tachycardia were studied. A steerable quadripolar catheter was positioned in 3 to 9 locations in the region between the site recording the His bundle electrogram and the coronary sinus (CS) os under flouroscopic and electroanatomic guidance. We mapped anterosuperior sites at or near sites with His potential recordings, and up to 2 mm inferior to the His bundle recording, posteroseptal sites included the CS os and sites along the posterior, superior, and inferior border of the CS. Atrial pacing was performed at a cycle length 50 ms longer than Wenckebach cycle length. Subthreshold stimulation was applied at a frequency of 10 Hz and 20 Hz delivered to the distal electrode pair. AH and HV intervals were recorded before and during subthreshold stimulation. AH prolongation was defined as a reproducible increase in AH interval by >10 ms from a stable baseline AH interval. RESULTS: Eight of 14 patients demonstrated prolongation of AV conduction at a mean of 1.75 +/- 0.2 sites. Mean AH prolongation was 56.4 +/- 13.0 ms (p = 0.02) from baseline. AH prolongation was achieved 15.4 +/- 1.8 mm below the His bundle recording in 7 patients, at the site of the His bundle recording in 3 patients, and along the posterior CS os border in 3 patients. CONCLUSION: Subthreshold stimulation prolongs AV nodal conduction only at specific sites within the triangle of Koch, suggesting discrete parasympathetic endocardial inputs into the AV nodal region.     

Electrical and hemodynamic function produced by stimulation of atropine sensitive right ventricular nerves in humans

In mammalian ventricles including humans, it is recognized that parasympathetic ganglia innervate the heart. Little is known about the location and function of right ventricular parasympathetic nerves in humans. We hypothesized that in humans: (1) there are parasympathetic ganglia that supply the right ventricle that can be stimulated via an endocardial catheter and (2) stimulation of these fibers will alter the electrical and hemodynamic function of the right ventricle. Parasympathetic nerve stimulation was performed via an endocardial catheter placed along several sites of the right ventricle, superior vena cava, and right internal jugular area in humans. The spatial extent of parasympathetic innervation was mapped in 1-cm zones across the right ventricle. Cardiac output, heart rate, and atrioventricular conduction were monitored to provide independent assessment of parasympathetic innervation. In all 22 patients, ventricular refractoriness shortened from 12 ± 3 to 3 ± 1 ms during parasympathetic nerve stimulation, and the greatest shortening of refractoriness was observed at the base of the right ventricle (p = 0.01). No significant shortening in ventricular refractoriness occurred in areas beyond 2 cm from the right ventricular base. These results were compared by using T table test. The parasympathetic nerve stimulation protocol decreased cardiac output, reaffirming the principle effect of parasympathetic ganglia. Atropine was administered in seven patients. All effects from nerve stimulation were abolished after atropine administration. These results were also compared by using T table test. These data provide the first demonstration of the electrical and hemodynamic function by stimulation of atropine sensitive nerves of the human right ventricle. Greater understanding of parasympathetic innervation may lead to novel therapies for arrhythmias.     

“Paradoxical” AH Shortening Caused By Proximal Coronary Sinus Stimulation During Orthodromic Reciprocating Tachycardia

AH Shortening During ORT. Introduction: During extrastimulation or entrainment of orthodromic atrioventricular (AV) reciprocating tachycardia (ORT), the atriuni-His (AH) interval as measured at the His-bundle recording site is expected to lengthen due to extrastimu-Lation-dependent or pacing rate-dependent slowing of AV nodal conduction by impulses that penetrate the tachycardia circuit. We report 6 patients in whom the AH interval “paradoxically” shortened during ORT in response to extrastimulation and rapid pacing from the proximal coronary sinus. Methods and Results: Accessory pathway location was right anterior (1 patient), right anteroseptal (1 patient), and left anterior (4 patients). Cycle length of ORT was stahle (variation ≤ 5 msec) and ranged from 325 to 410 msec. During ORT, extrastimulation and rapid pacing were performed from the proximal coronary sinus and the right atrium. Extrastimulation from the proximal coronary sinus late in diastole caused significant shortening of AH interval in all patients hy a mean of 18 ± 3 msec (range 15 to 20 msec). AH shortening was demonstrated without a change of either the timing or morphologic appearance of the low septal right atrium at the H is-bundle recording site. This phenomenon was not ohserved during right atrial extrastimulation. Rapid pacing from the proximal coronary sinus at cycle lengths of 305 to 390 msec (i.e., 15 to 20 msec shorter than the cycle length of each ORT) again demonstrated shortening of AH interval in all patients by a mean of 15 ± 3 msec (range 10 to 20 msec). By contrast, rapid pacing from the right atrium demonstrated classical AH prolongation at any paced cycle length. Conclusion: AH shortening without a change of either the timing or morphologic appearance of the low septal right atrium at the His-handle recording site confirms the existence of a distinct posterior atrial input to the AV node. In this setting low septal right atrial activation is not requisite for AV nodal conduction. Whether activation of the low septal right atrium is essential for. or contributes to, AV nodal conduction of atrial impulses from locations other than the proximal coronary sinus needs to he determined.     

Prospective Study of Autonomic Nerve Function in Type 1 and Type 2 Diabetic Patients: 24 Hour Heart Rate Variation and Plasma Motilin Levels Disturbed in Parasympathetic Neuropathy

To clarify the impact of autonomic neuropathy in diabetic patients, we have conducted a prospective study of 58 Type 1 and 51 Type 2 diabetic patients (investigated at baseline, after 4, and after 7 years). In Type 1 diabetic patients, the sympathetic nerve function (orthostatic acceleration and brake indices) and in Type 2 patients, parasympathetic nerve function (R-R interval variation; E/I ratio) deteriorated during 7 years of prospective observation. Symptoms of autonomic neuropathy were associated with signs of autonomic neuropathy (low brake indices) in Type 1 but not in Type 2 diabetic patients. In the latest assessment 24 h ECG recording was performed and blood samples assayed for neuropeptide Y (NPY) and motilin were obtained. Type 1 diabetic patients with parasympathetic neuropathy (abnormal E/I ratio) showed significantly lower SD value (less variation in the R-R intervals; 29 [17] vs 50 [16], [mean {interquartile range}]; p = 0.001) and higher postprandial plasma motilin values (70 [20] pmol I^?1 vs 50 [15] pmol I^?1; p< 0.01) than patients with normal parasympathetic nerve function. In Type 2 diabetic patients, sympathetic neuropathy (low brake indices) was associated with an increased frequency of ventricular extra systolic beats during 24 h ECG recording (r_s = 0.65; p<0.01). Postprandial plasma NPY levels were not associated with disturbed autonomic nerve function.     

Electrophysiology and long-term efficacy of pentisomide in patients with supraventricular tachycardia.

The electrophysiologic effects of pentisomide were investigated after intravenous (5 mg/kg) and oral (900-1200 mg three times a day) application in 9 patients with drug refractory atrioventricular nodal tachycardia and 6 patients with orthodromic atrioventricular re-entrant tachycardia. Pentisomide did not change sinus cycle length, effective refractory period of the right ventricle and the atrioventricular node. AH, HV interval, effective refractory period of the right atrium, QRS duration and QTc duration were (p less than or equal to 0.01) increased. Tachycardia cycle length was only increased after intravenous application of pentisomide, antegrade effective refractory periods of the accessory pathways and shortest fully pre-excited R-R intervals during atrial fibrillation were increased after the oral treatment phase (p = 0.054). Intravenous pentisomide prevented tachycardia in 6/9 patients with atrioventricular nodal tachycardia and in 2/6 patients with atrioventricular re-entrant tachycardia. If intravenous pentisomide did not prevent induction of the tachycardia, oral pentisomide was not effective either. During long-term follow-up 2/7 patients with atrioventricular nodal tachycardia and 1/4 patient with atrioventricular re-entrant tachycardia had a recurrence. Long-term treatment with pentisomide had to be discontinued because of possible side effects in 2 patients. It is concluded, that the electrophysiological effects of pentisomide are similar to those of flecainide and propafenone.     

Heart Rate Variability: Does it Change After RF Ablation of Reentrant Supraventricular Tachycardia?

Background: Following RF ablation of reentrant supraventricular tachycardia, inappropriate sinus tachycardia may occur. Local parasympathetic denervation is a possible mechanism for these rhythm disturbances. The purpose of this study was to determine the incidence of sinus tachycardia and to determine the relation between endocardial lesions at different ablation sites and alterations in autonomic tone in several different groups of patients with supraventricular tachycardia, using techniques of heart rate variability analysis. Methods: The subjects of this study were 75 patients (48 women, 27 men) with a mean age of 39.99 (SD = 13.39). They underwent RF ablation of AV nodal slow pathways (40 cases), posteroseptal APs (23 cases), left lateral and right free wall APs (12 cases) because of symptomatic tachycardias. The mean sinus rate and time domain (standard deviation of RR intervals and root mean square of differences of adjacent RR intervals) and frequency domain (low frequency, high frequency and low frequency/high frequency ratio) analyses of heart rate variability were obtained by use of 24 hour Holter monitoring before and 1 month after ablation compared with pre-ablation values. Results: Analysis of 24 hour ambulatory Holter-monitors, performed 1 month after RF ablation, showed no significant changes in time and frequency domain parameters of heart rate variability in different groups. A significant increase in mean heart rate was noted after RF ablation at AV nodal slow pathway group and left freewall/right free wall accessory pathways group. Patients undergoing RF ablation of right or left posteroseptal accessory pathways had no significant increase in the mean heart rate. Conclusion: In summary, an increase in sinus tachycardia may be initiated by RF ablation of atrioventricular reentrant tachycardia (AVNRT) and right free wall or left free wall accessory pathways. This finding shows that the modifications of heart rate are not directly related to the posteroseptal region or to the accessory pathways.     

干预犬下腔静脉脂肪垫对窦房结及房室结功能的影响

目的通过不同干预方法,观察犬下腔静脉脂肪垫对窦房结及房室结功能的影响。方法选择16只犬开胸暴露下腔静脉脂肪垫,首先以固定的输出频率(20Hz)连续电刺激下腔静脉脂肪垫30 s,测量刺激前和刺激时窦房结恢复时间(SNRT)、校正SNRT(cSNRT)及AH、HV、RR间期变化;然后在直视下心外膜射频消融脂肪垫,再测定迷走神经刺激前后上述指标的变化。结果:14只完成试验。当电刺激下腔静脉脂肪垫时,AH间期与刺激前比较明显延长(122.2±12.4 m s vs 82.5±10.3 m s,P<0.05),其余指标未发生明显变化。电刺激通常在2 s内起效,AH间期随刺激电压增加而延长,在刺激停止3 s内恢复。射频消融下腔静脉脂肪垫后,刺激左右颈部迷走神经,SNRT、cSNRT及RR间期与刺激前比较有明显变化(分别为696.4±54.9 m s vs 467.5±45.4 m s;296.3±20.5 m svs 164.5±20.1 m s,400.3±39.1 m s vs 210.1±14.5 m s,P均<0.05),但AH间期及HV间期未发生明显变化。结论:刺激下腔静脉脂肪垫可使房室传导延迟,而不影响窦房结功能。消融下腔静脉脂肪垫可以消除迷走神经对房室结的支配。     

Role of force – frequency relation during AV–block,sinus node block and betaadrenoceptor block in conscious animals

Objective Myocardial contractility is regulated by adrenergic stimulation, the strength–length relationship and the force–frequency relationship or Bowditch effect. The latter mechanism was clearly demonstrated in muscle strips, in the isolated heart as well as in in–vivo experiments. The aim of this study was to further investigate the role of the force–frequency effect on the contractile response to exercise or isoproterenol infusion in conditions of restricted increases in heart rate i.e., AV–block, sinus node block and beta–adrenoceptor block. Methods Nineteen dogs were instrumented with a left ventricular miniature pressure gauge, catheters in the aorta, pulmonary artery and left atrium and pacing leads on the left atrium and left ventricle. In order to control the chronotropic response during sympathetic stimulation, permanent AV–block was induced in nine dogs, sinus node block using UL–FS 49 and beta–adrenoceptor block using propranolol was studied in ten dogs. Results Adrenergic stimulation (isoproterenol 0.4 µg/kg or exercise) after total AV–block failed to increase LVdP/dt. However, increasing LV pacing rate (from 50 up to 200 bpm) prior to adrenergic stimulation elicited a significant increase in LVdP/dt (4762 ± 166 mmHg/s vs. 6485 ± 381 mmHg/s, p < 0.05). In dogs in sinus rhythm, heart rate and LVdP/dt response to isoproterenol and exercise following pre–treatment with UL-FS 49 is significantly reduced, with heart rate increasing from 103 ± 7 up to 154 ± 5 bpm and LV dP/dt_max from 2925 ± 171 mmHg/s to 6249 ± 400 mmHg/s compared to the response in control conditions (HR 220 ± 3 bpm and LV dP/dt_max 7473 ± 616 mmHg/s) (p < 0.05). When heart rate is matched using atrial pacing, the LVdP/dt_max response reached comparable values as observed in control conditions (7310 ± 550 mmHg/s). Similar responses were obtained during exercise. Beta–adrenoceptor blockade attenuates considerably the heart rate and LVdP/dt response to sympathetic stimulation. Adjusting heart rate with atrial pacing restores only partially LVdP/dt_max. Conclusion During sympathetic stimulation, the chronotropic response plays a major role for the concomitant full expression of the inotropic response. In conditions where increases in heart rate are absent or severely restricted such as in permanent AV–block, sinus node block and beta–adrenoceptor block, the inotropic response will also be impaired.