Ventriculophasic modulation of atrioventricular nodal conduction in humans

BACKGROUND: Baroreceptor-mediated phasic changes in vagal tone have been hypothesized to cause ventriculophasic sinus arrhythmia (VPSA). The objectives of this study were to demonstrate ventriculophasic modulation of AV nodal conduction and to substantiate the role of the baroreflex on ventriculophasic AV nodal conduction (VPAVN) by pharmacological perturbation of parasympathetic tone. METHODS AND RESULTS: Twelve patients with infra-Hisian second-degree heart block and VPSA were studied. Incremental atrial pacing was performed until AV nodal Wenckebach block at baseline, after phenylephrine infusion, and after atropine. AV nodal conduction curves were constructed for each phase and compared. At baseline, VPAVN was present in 9 of 12 patients on the steep portion of the AV nodal conduction curves. Phenylephrine increased systolic blood pressure from 149+/-33 to 177+/-22 mmHg (P<0.001) and sinus cycle length from 844+/-169 to 1010+/-190 ms (P<0.001) and shifted the AV nodal conduction curves up and to the right. Phenylephrine induced VPAVN in 2 of 3 patients in whom it was not present at baseline and in 11 of 12 total. Atropine abolished both VPSA and VPAVN in all patients. CONCLUSIONS: VPAVN was demonstrated in patients with infra-Hisian second-degree AV block. It was accentuated by phenylephrine and abolished by atropine, suggesting a baroreflex mechanism for VPSA and VPAVN.     

Catheter ablation for the common type of atrioventricular nodal reentrant tachycardia

Radiofrequency (RF) catheter ablation of the slow AV nodal pathway was attempted in 34 patients with common type of AV nodal reentrant tachycardia (AVNRT). Radiofrequency energy of 18-32 watts was applied for 30-60 seconds at sites exhibiting atrial-slow pathway potentials or slow potentials. These potentials were recorded at the mid or posterior septum, anterior to the coronary sinus ostium. A mean of two radiofrequency applications successfully eliminated AVNRT in all patients. The incidence of junctional ectopy was significantly higher during 34 effective applications of radiofrequency energy than during 36 ineffective applications (100% versus 17%). Thus, the recording of atrial-slow pathway potentials or slow potentials, and the development of junctional ectopy can be used as a marker for successful ablation. Slow AV nodal conduction was eliminated in 22 patients and persisted without inducible AVNRT in 12. None of the patients had recurrences of AVNRT over a mean follow-up interval of 12 months, and all had preserved AV conduction. Long-term follow-up studies with an electrophysiological method confirmed that the ablation was effective. Transient AV block was observed in only 1 patient, and no major complications were noted. Thus, radiofrequency catheter ablation of the slow AV nodal pathway is highly effective and safe, with a low rate of complication, for the treatment of common type of AVNRT.     

Cardiovascular action of verapamil in the dog with particular reference to myocardial contractility and atrioventricular conduction

Verapamil (Isoptin) caused a dose-dependent peripheral vasodilation, increase in myocardial contractility, and tachycardia in the anaesthetized dog. Propranolol pretreatment blocked the cardiac stimulation following verapamil but the vasodilation was unaltered. Inflation of a thoracic aortic balloon prevented the fall in intravascular pressure and reduced the tachycardia and positive inotropic responses. These experiments suggest that clinical doses of verapamil cause peripheral vasodilation which leads to a sympathetic reflex induced increase in heart rate and myocardial contractility. Verapamil also had a direct myocardial depressant action which became evident at doses above the range used clinically. The drug increased the PR interval in conscious dogs for up to 60 minutes. This effect was partly mediated through cholinergic stimulation and partly through a direct depression on atrioventricular conduction.     

Case report: radiofrequency catheter ablation of atrioventricular nodal reentrant tachycardia in a patient with heart transplantation

We have assessed hepatocellular integrity in patients anaesthetized with desflurane or isoflurane using glutathione transferase Alpha (GSTA) as a sensitive indicator. Volatile anaesthetic was administered to 72 women at 0.7 MAC for 25 min and thereafter at 1.0 MAC. GSTA was measured with a time-resolved immunofluorometric assay in serum samples. Mild or moderate increases in GSTA were found in approximately 40% of patients immediately after anaesthesia. In the desflurane group (n = 30) the increase in GSTA concentration was from a baseline value of the geometric mean of 1.3 microgram litre-1 (95% confidence interval 0.9-1.9 microgram litre-1) to a peak of 2.6 (1.8-3.8) micrograms litre-1. The corresponding increase in the isoflurane group (n = 31) was from 1.3 (0.9-1.9) microgram litre-1 to 3.0 (2.2-4.2) micrograms litre-1. The change in GSTA concentration was significant in both groups but not between groups. No predictive factors for the increase in GSTA concentrations were found. Increased GSTA concentrations were not accompanied by increases in amino-transferases. We conclude that desflurane and isoflurane anaesthesia were associated with a mild subclinical disturbance of hepatocellular integrity.     

Preceding His-atrial interval as a determinant of atrioventricular nodal conduction time in the human and rabbit heart

This investigation shows that atrioventricular (A-V) nodal conduction time (A-H interval), both in the human and in the isolated rabbit heart, is determined mainly by the length of the preceding His-atrial (H-A) interval. The A-H intervals obtained during atrial extrasystolic stimulation at different basic rates, during Wenckebach cycles and during both transient and steady state responses to stepwise increases in stimulation frequency were plotted against the corresponding H-A intervals. The A-H intervals were found to have nearly the same duration provided they were preceded by the same H-A interval. The only important difference appeared in the short H-A interval range as a shortening of the A-H interval at faster basic rates. This facilitating effect of frequency, which was found in the majority of cases, is compatible with the similarly frequency-dependent shortening of the functional refractory period of the A-V node.     

Absence of junctional rhythm during successful slow-pathway ablation in patients with atrioventricular nodal reentrant tachycardia

BACKGROUND: The presence of junctional rhythm has been considered to be a sensitive marker of successful slow-pathway ablation. However, in rare cases, junctional rhythm was absent despite multiple radiofrequency applications delivered over a large area in the Koch's triangle, and successful ablation was achieved in the absence of a junctional rhythm. METHODS AND RESULTS: This study included 353 patients with AV nodal reentrant tachycardia (143 men and 210 women; mean age, 50+/-17 years) who underwent catheter ablation of the slow pathway. Combined anatomic and electrogram approaches were used to guide ablation. Inducibility of AV nodal reentrant tachycardia was assessed after each application of radiofrequency energy. Successful sites were located in the posterior area in 18 (90%) of 20 patients without junctional rhythm during slow-pathway ablation compared with 200 (60%) of 333 patients with junctional rhythm (P<0.001). The fast-slow form of tachycardia was more common in patients without than in those with junctional rhythm (30% versus 3%; P=0.001). At the successful ablation sites, patients with junctional rhythm had a higher incidence of a multicomponent or slow-pathway potential (51% versus 10%; P<0.001), a longer duration of the atrial electrogram (64+/-8 versus 50+/-9 ms; P=0.04), and a smaller atrial/ventricular electrogram amplitude ratio (0.29+/-0.18 versus 0.65+/-0.27; P<0. 001) than those without junctional rhythm. Mean temperatures at successful sites (56+/-6 degreesC versus 58+/-9 degreesC; P=0.57) and incidence of transient AV block (2% versus 0%; P=0.86) were similar between patients with and without junctional rhythms. By multivariate analysis, location of ablation sites, atrial/ventricular electrogram amplitude ratio, absence of a multicomponent or slow-pathway potential, and occurrence of the fast-slow form of tachycardia were independent predictors of the absence of a junctional rhythm during successful slow-pathway ablation. CONCLUSIONS: In some rare cases, successful slow-pathway ablation is possible in the absence of a junctional rhythm.     

Architecture of the atrial musculature in and around the triangle of Koch: its potential relevance to atrioventricular nodal reentry

INTRODUCTION: Recent studies suggest that atrial fibers in the approaches to the AV node form part of the dual pathways recognized electrophysiologically in patients with AV nodal reentrant tachycardia (AVNRT). Our aim was to determine, by gross dissection, the arrangement of the superficial musculature in the area of the triangle of Koch in normal hearts and in hearts with documented AVNRT, hoping to ascertain anatomic features that might contribute to the debate. METHODS AND RESULTS: We used blunt dissection to study the architecture of the superficial atrial musculature in 16 autopsied hearts from adults who died of noncardiac disease. A well-defined pattern of architecture of muscle fibers was found in the region of the triangle of Koch, showing marked variations in 7 of the 16 specimens. The relationship of these fibers to the histologically specialized AV node was confirmed by histology in three cases. Two hearts from patients with known AVNRT, treated by ablation in one, were examined further histologically. These sections showed that the site of ablation was well distant from the histologically discrete AV node. CONCLUSION: The variability in the arrangement of the superficial atrial muscle fibers in the area of the triangle of Koch may be one of the factors influencing the route for impulses entering the AV node. Lesions that ablate nodal reentry are within these atrial fibers rather than the histologically specialized AV node.     

Successful ablation of atrioventricular nodal reentry tachycardia in a patient with persistent left superior vena cava

We report the case of a patient with atrioventricular nodal reentry tachycardia associated with persistent left superior vena cava draining to a large coronary sinus. Successful ablation was performed at the level of the superior lip of the coronary sinus ostium.     

Selective functional properties of dual atrioventricular nodal inputs. Role in nodal conduction, refractoriness, summation, and rate-dependent function in rabbit heart

BACKGROUND: The atrioventricular node receives its activation signal from the low crista terminalis and low interatrial septum, the summation of which is believed to favor conduction. A functional asymmetry between the inputs is also believed to be involved in nodal reentrant rhythms. We studied the selective functional characteristics of nodal inputs and determined their role in nodal conduction, refractoriness, summation, and rate-dependent function. METHODS AND RESULTS: The nodal properties of recovery, facilitation, and fatigue were characterized with stimulation protocols applied with varying phases between the two inputs in isolated rabbit heart preparations. The effects of the input phase, nodal functional state, and input reference on the nodal conduction time, recovery time, and refractory periods were assessed with multifactorial ANOVAs. It was found that the phase of stimulation significantly affected nodal conduction time but not the refractory periods or the time constant of the recovery. Each input could show longer and shorter conduction time than the other depending on the stimulation phase, input reference, and coupling interval. These effects were similar for different nodal functional states. However, pacing and recording from the low crista resulted in similar conduction and refractory values than did pacing and recording from the low septum. Input summation did not increase the otherwise equal efficacy of individual input in activating the node. Nodal surface recordings confirmed this functional symmetry and equivalent efficacy of the inputs and showed that input effects were confined to the proximal node. CONCLUSIONS: The two nodal inputs have equivalent functional properties and are equally effective in activating the rate-dependent portion of the node. Input interaction affects perinodal activation but not the rate-dependent nodal function.     

Randomized comparison of anatomic and electrogram mapping approaches to ablation of the slow pathway of atrioventricular node reentrant tachycardia

OBJECTIVES: The purpose of this study was to prospectively compare in random fashion an anatomic and an electrogram mapping approach for ablation of the slow pathway of atrioventricular (AV) node reentrant tachycardia. BACKGROUND: Ablation of the slow pathway in patients with AV node reentrant tachycardia can be performed by using either an anatomic or an electrogram mapping approach to identify target sites for ablation. These two approaches have never been compared prospectively. METHODS: Fifty consecutive patients with typical AV node reentrant tachycardia were randomly assigned to undergo either an anatomic or an electrogram mapping approach for ablation of the slow AV node pathway. In 25 patients randomly assigned to the anatomic approach, sequential radiofrequency energy applications were delivered along the tricuspid annulus from the level of the coronary sinus ostium to the His bundle position. In 25 patients assigned to the electrogram mapping approach, target sites along the posteromedial tricuspid annulus near the coronary sinus ostium were sought where there was a multicomponent atrial electrogram or evidence of a possible slow pathway potential. If the initial approach was ineffective after 12 radiofrequency energy applications, the alternative approach was then used. RESULTS: The anatomic approach was effective in 21 (84%) of 25 patients, and the electrogram mapping approach was effective in all 25 patients (100%) randomly assigned to this technique (p = 0.1). The four patients with an ineffective anatomic approach had a successful outcome with the electrogram mapping approach. On the basis of intention to treat analysis, there were no significant differences between the electrogram mapping approach and the anatomic approach with respect to the time required for ablation (28 +/- 21 and 31 +/- 31 min, respectively, mean +/- SD, p = 0.7) duration of fluoroscopic exposure (27 +/- 20 and 27 +/- 18 min, respectively, p = 0.9) or mean number of radiofrequency applications delivered (6.3 +/- 3.9 vs. 7.2 +/- 8.0, p = 0.6). With both the anatomic and electrogram mapping approaches, the atrial electrogram duration and number of peaks in the atrial electrogram were significantly greater at successful target sites than at unsuccessful target sites. CONCLUSIONS: The anatomic and electrogram mapping approaches for ablation of the slow AV nodal pathway are comparable in efficacy and duration. If the anatomic approach is initially attempted and fails, the electrogram mapping approach may be successful at sites outside the areas targeted in the anatomic approach. With both the anatomic and electrogram mapping approaches, there are significant differences in the atrial electrogram configuration between successful and unsuccessful target sites.     

Differential effect of adenosine on anterograde and retrograde fast pathway conduction in patients with atrioventricular nodal reentrant tachycardia

INTRODUCTION: Several studies have shown that the fast pathway is more responsive to adenosine than the slow pathway in patients with AV nodal reentrant tachycardia. Little information is available regarding the effect of adenosine on anterograde and retrograde fast pathway conduction. METHODS AND RESULTS: The effects of adenosine on anterograde and retrograde fast pathway conduction were evaluated in 116 patients (mean age 47 +/- 16 years) with typical AV nodal reentrant tachycardia. Each patient received 12 mg of adenosine during ventricular pacing at a cycle length 20 msec longer than the fast pathway VA block cycle length and during sinus rhythm or atrial pacing at 20 msec longer than the fast pathway AV block cycle length. Anterograde block occurred in 98% of patients compared with retrograde fast pathway block in 62% of patients (P < 0.001). Unresponsiveness of the retrograde fast pathway to adenosine was associated with a shorter AV block cycle length (374 +/- 78 vs 333 +/- 74 msec, P < 0.01), a shorter VA block cycle length (383 +/- 121 vs 307 +/- 49 msec, P < 0.001), and a shorter VA interval during tachycardia (53 +/- 23 vs 41 +/- 17 msec, P < 0.01). CONCLUSION: Although anterograde fast pathway conduction is almost always blocked by 12 mg of adenosine, retrograde fast pathway conduction is not blocked by adenosine in 38% of patients with typical AV nodal reentrant tachycardia. This indicates that the anterograde and retrograde fast pathways may be anatomically and/or functionally distinct. Unresponsiveness of VA conduction to adenosine is not a reliable indicator of an accessory pathway.     

Radiofrequency catheter ablation of atrioventricular junctional ("AV nodal") reentrant tachycardia in patients with implantable cardioverter defibrillators

Catheter ablation of tachycardias has been undertaken successfully in patients with ICDs without damage to the ICD or lead. Ablation of the slow AV nodal pathway, however, is technically challenging because the lead of the ICD lies close to the ablation site. We report successful ablation of AV junctional reentrant tachycardia (AVJRT) in three patients with ICDs. In all cases, the ablation site was within a few millimeters of the ICD lead. The ablation was successful in all cases and did not cause damage to the ICD or lead. The patients have remained free of recurrence of AVJRT during a mean follow-up of 12 months.     

A randomized comparison of fixed power and temperature monitoring during slow pathway ablation in patients with atrioventricular nodal reentrant tachycardia

In the present study, using sodium dodecyl sulphate-polyacrylamide gel electrophoresis and Western blot techniques, the patterns of proteins extracted from C. neoformans yeast cells were analysed. A major 105 kilodalton (kDa) antigen that binds to Concanavalin A and cross-reacts with anti-mannan antibodies was identified. The 105 kDa mannoprotein, highly expressed in the acapsular mutant of C. neoformans with respect to the encapsulated strain, is involved in the lymphoproliferative response of T lymphocytes to Cryptococcus-sensitized monocytes.     

The pharmacokinetics of metoclopramide in man with observations in the dog

1 The pharmacokinetics of metoclopramide have been studied in eight normal male volunteers. 2 The mean plasma beta half-life was 156.7 min after i.v. administration of 10 mg metoclopramide. 3 After oral dosing of 10 mg the mean half-life was 196.6 min and after 20 mg 317.5 min (P less than 0.05). 4 Bioavailability of a 10 mg oral dose of metoclopramide varied between 32 and 97%. 5 A major urinary metabolite was metoclopramide-N-4-sulphate and the amounts of conjugates appearing in urine to 24 h correlated significantly with the bioavailability. 6 In the dog the metabolic fate of metoclopramide is different to man with conjugation being a minor metabolic pathway. The half-life in the dog does not appear to be dose dependent. 7 The wide differences in bioavailability of metoclopramide in man may contribute to the unpredictable occurrence of side effects.