A canine model of atrial flutter following the intra-atrial lateral tunnel Fontan operation.

Atrial flutter (AFL) is a common problem in children who have undergone a Fontan operation for single ventricle physiology. Although this has been attributed to the atrial stretch inherent in the earlier forms of this operation, AFL has persisted in spite of a modification that minimizes atrial distension. Therefore, it was hypothesized that AFL following the modified Fontan procedure may result from anatomic barriers related to suture lines rather than from atrial stretch or hypertension. In a series of experiments performed in dogs under general anesthesia, the modified Fontan repair was simulated by placing only the suture line of the intra-atrial repair. No baffle was placed, thus avoiding any hemodynamic alterations. After closure of the atriotomy, 253 point unipolar atrial endocardial form-fitting electrodes were inserted through the mitral and tricuspid valves via bilateral ventriculotomies. Induction of AFL was attempted with atrial burst pacing and programmed extrastimulation, and activation sequence maps of subsequent reentry were generated from the endocardial electrodes. Atrial flutter was induced in all of 17 dogs, with a median cycle length of 177 +/- 31 ms. Activation sequence maps demonstrated conduction block along the crista terminalis corresponding to the free wall portion of the suture line. This created an isthmus between the suture line and tricuspid annulus, which appeared critical for sustaining AFL, although the circuit used both the septal and free wall surfaces of the right atrium. In seven dogs, a cryolesion was placed from the tricuspid annulus to the free wall segment of the suture line, terminating the AFL, in all seven. When the free wall segment of the suture line was moved 5 mm medial to the crista terminalis, AFL was induced in four of five dogs, but only in the presence of isoproterenol and at a shorter cycle length (136 +/- 8 ms, P < .001). Atrial flutter was not inducible, even with the addition of isoproterenol, in any of five dogs in which the suture line was placed 10 mm anterior to the crista terminalis and incorporated into closure of the atriotomy. This acute canine model of the modified Fontan operation demonstrates that conduction block from the free wall portion of the suture line creates an isthmus of tissue between the suture line and the tricuspid annulus. This is a sufficient substrate to produce AFL; no hemodynamic alteration is required. Injury to the crista terminalis is a significant risk factor in this model, which suggests that a modification of the suture line might reduce the incidence of AFL in patients following this operation.

Spontaneous atrial flutter in a chronic canine model of the modified Fontan operation.

OBJECTIVES: This study sought to 1) establish whether the atrial flutter (AFL) inducible acutely occurs spontaneously in a chronic canine model, and 2) characterize any reentrant circuits present chronically. BACKGROUND: We previously demonstrated, in an acute canine model of the modified Fontan operation, that the lateral tunnel suture line creates a sufficient electrophysiologic substrate for AFL. METHODS: Using cardiopulmonary bypass, a suture line was placed through a right atriotomy in adult dogs (n = 7) to simulate the lateral tunnel of the Fontan operation. Holter recordings were made preoperatively, on the first postoperative day and 2, 4 and 6 weeks postoperatively. At 6 to 8 weeks, through bilateral ventriculotomies, 253-point unipolar atrial electrodes were inserted. AFL was induced using atrial burst pacing, and endocardial activation sequence maps were created. RESULTS: Preoperatively, all dogs were in sinus rhythm. Spontaneous AFL occurred in all dogs postoperatively, with a mean (+/-SD) cycle length of 192 +/- 22 ms. At 6 weeks postoperatively, of six dogs that survived, four had intermittent AFL, and two had incessant AFL. At reoperation, sustained AFL was inducible in six of six dogs, with a mean cycle length of 194 +/- 17 ms. Activation sequence maps demonstrated conduction block at the lateral tunnel suture line, which facilitated unidirectional conduction critical for propagation of the reentrant circuit. The AFL circuit was similar to that observed acutely. CONCLUSIONS: In a chronic canine model of the modified Fontan operation, the lateral tunnel suture line alone, in the absence of atrial stretch or hypertension, provides an electrophysiologic substrate that promotes spontaneous AFL. This model may be useful for evaluating various forms of treatment and prevention of AFL after the Fontan operation.

Anatomically based ablation of atrial flutter in an acute canine model of the modified Fontan operation.

BACKGROUND: Lateral tunnel total cavopulmonary connection, also called the modified Fontan operation, uses a baffle through the right atrium. We established, in an acute canine model, that atrial flutter after total cavopulmonary connection revolves around a line of conduction block imposed by the free wall lateral tunnel suture line. We hypothesized that a line of conduction block between the free wall total cavopulmonary connection suture line and the tricuspid anulus would interrupt atrial flutter in this model. OBJECTIVE: Our objective was to determine whether a cryolesion placed between the free wall total cavopulmonary connection suture line and the tricuspid anulus would terminate atrial flutter in an acute canine model. METHODS: Seven adult dogs underwent median sternotomy and institution of cardiopulmonary bypass. A suture line was placed through a right atriotomy to simulate total cavopulmonary connection lateral tunnel construction. Form-fitting 253-point biatrial endocardial mapping electrodes were placed via bilateral ventriculotomies. Atrial flutter was induced by atrial burst pacing. A cryothermal lesion was then placed between the free wall total cavopulmonary connection suture line and the tricuspid anulus in the low lateral right atrium (i.e., CRYO 1 procedure), and reinduction of atrial flutter was attempted. If atrial flutter was reinduced, the cryolesion was modified superiorly to include the caudal portion of the atriotomy (i.e., CRYO 2 procedure). Activation sequence maps were generated for sinus rhythms before and after the cryolesions were placed and for induced arrhythmias. RESULTS: In all seven cases, atrial flutter was inducible after suture line placement, before placement of a cryolesion. The reentrant circuit incorporated both caval orifices in five of seven cases and was successfully ablated by the CRYO 1 approach in each case. Atrial flutter was not inducible after placement of the CRYO 2 lesion in the remaining two cases, in which breakthrough of the wave front occurred across the lateral tunnel suture line in the intercaval region. Activation sequence maps of sinus rhythm after placement of the cryolesions demonstrated a conduction block at the site of the lesion. CONCLUSIONS: A linear cryothermal lesion placed between the free wall aspect of the total cavopulmonary connection suture line and the tricuspid anulus created a line of conduction block that successfully ablates atrial flutter in the canine model.

Atrial flutter: a newly recognized complication of pediatric lung transplantation.

BACKGROUND AND METHODS: Atrial flutter after pediatric lung transplantation has not previously been reported. We reviewed the records of 78 children who underwent lung transplantation at our institution to characterize the incidence and clinical course of postoperative atrial flutter. The diagnosis was based on either a surface or transesophageal electrocardiogram that demonstrated a fixed cycle length atrial tachycardia that did not require ventricular participation. RESULTS: Atrial flutter occurred in seven of 62 (11.3%) patients who underwent bilateral sequential lung transplantation, zero of 10 patients after single lung transplantation, and zero of six patients after heart-lung transplantation. Ages of the patients with atrial flutter ranged from 2.5 months to 14 years. Electrocardiographic findings among patients varied with respect to p-wave morphology and atrioventricular conduction. No patient had a prior atrial arrhythmia or coexisting structural cardiac disease. None had atrial flutter in relation to a rejection episode. Two patients had atrial flutter transiently during the first postoperative day, but it resolved spontaneously. Five patients had recurrent atrial flutter that began 13 +/- 7 days after the operation. The mean cycle length of atrial flutter was 196 +/- 65 msec. The arrhythmia was unresponsive to digoxin in four patients to whom it was administered. It was controlled with procainamide in four patients and with flecainide in one. At 1 and 6 months after lung transplantation, procainamide was discontinued in two patients without recurrence. One patient died of bronchiolitis obliterans 6 months after the operation while still receiving flecainide. Two patients continue to receive procainamide 4 and 7 months after transplantation. CONCLUSIONS: (1) Atrial flutter commonly occurs after bilateral lung transplantation in children. (2) Electrocardiographic manifestations are variable. (3) Type 1 antiarrhythmic agents provide satisfactory control.

Left-sided atrial flutter: characterization of a novel complication of pediatric lung transplantation in an acute canine model.

BACKGROUND: Postoperative atrial flutter has been observed in approximately 10% of children undergoing lung transplantation at our institution. We hypothesized that the left atrial anastomoses made to establish pulmonary venous continuity provide the primary electrophysiologic substrates for atrial flutter. OBJECTIVES: Our objectives were (1) to determine whether the left atrial suture lines alone are sufficient to produce atrial flutter in an acute canine model of lung transplantation and (2) to characterize any resulting reentrant circuits to surgically ablate the atrial flutter. METHODS: Supported by cardiopulmonary bypass, adult dogs (n = 10) underwent bilateral pneumonectomies. The left atrial anastomotic suture lines were simulated by dividing the tissue between the ostia of the transected superior and inferior pulmonary veins and closing the resulting defects. Bilateral suture lines were placed in group 1 (n = 6) to simulate bilateral lung transplantation. In group 2 (n = 4), only a left-sided suture line was placed to represent single lung transplantation. Unipolar 253-point biatrial endocardial mapping electrodes were inserted via bilateral ventriculotomies. Atrial flutter was induced by atrial burst pacing, and activation sequence maps were generated. In five of six cases in group 1, a T-incision connecting the two suture lines and the mitral anulus was then made. In group 2, a single incision from the suture line to the mitral anulus was performed in each case. Burst pacing was subsequently repeated. RESULTS: Atrial flutter could not be induced after bypass alone in any case. After simulated lung transplantation, sustained atrial flutter was reproducibly induced in 10 of 10 dogs. The mean cycle length in all dogs was 133 +/- 7 msec. There was no significant difference in mean cycle length or activation sequence patterns between groups 1 and 2. The reentrant circuit was confined to the left atrium. Each simulated left atrial anastomosis created a zone of conduction block around which circus movement could occur. In group 1, either suture line functioned as the central obstacle. Atrial flutter was terminated in five of five dogs in group 1 by means of the T-incision and in all four dogs in group 2 with the incision connecting the suture line to the mitral anulus. CONCLUSIONS: (1) In an acute canine model of lung transplantation, each left atrial suture line alone provides an electrophysiologic substrate for atrial flutter by creating a zone of conduction block around which circus movement can occur. (2) Extending this zone of block to the mitral anulus, together with interruption of the isthmus of tissue between the two suture lines present after bilateral lung transplantation, terminates the atrial flutter in this model and may have an application prophylactically at the time of lung transplantation in children to prevent postoperative atrial flutter.

Risk of radiation induced skin injuries from arrhythmia ablation procedures.

Catheter guided ablation of cardiac arrhythmias is an effective and safe procedure for the treatment of most supraventricular and selected ventricular tachycardias. Because catheter manipulation is fluoroscopically guided, there is risk of radiation induced injury, especially during prolonged procedures. The Food and Drug Administration has recently issued a bulletin warning of the risks of acute skin injury occurring during fluoroscopically guided procedures that result in an exposure level exceeding 2 Gray units (Gy). This study was performed as an investigation into the risk of radiation induced skin injury during arrhythmia ablation procedures. The amount of radiation exposure for 500 patients who underwent ablation was calculated based upon fluoroscopy times and the entrance dose of radiation (0.02 Gy/min). The mean radiation exposure was 0.93 +/- 0.62 Gy. Although 5.6% of patients (n = 28) received enough radiation exposure to reach the threshold dose (2 Gy) for early transient erythema, no clinical manifestations of acute radiation induced skin injury were observed. No patients achieved the threshold dose for irreversible skin injury. Patients undergoing AV node ablation or modification received significantly less radiation (0.39 +/- 0.40 Gy and 0.79 +/- 0.44 Gy, respectively) than patients undergoing other ablation procedures (0.94-1.45 Gy, P < 0.05). There was no association between the magnitude of radiation exposure and the presence of underlying heart disease. Patients undergoing ablation of accessory pathways were exposed to more radiation if there was a right-sided pathway (1.69 +/- 0.93 Gy) compared to other sites (0.87-1.24 Gy, P < 0.05). This study demonstrates that the risk of significant radiation induced skin injury during arrhythmia ablation procedures is low provided that precautions are taken to minimize radiation exposure.

Catheter ablation of clinical intraatrial reentrant tachycardias resulting from previous atrial surgery: localizing and transecting the critical isthmus.

OBJECTIVES: We sought to evaluate the efficacy of anatomically based radiofrequency catheter ablation for the treatment of intraatrial reentrant tachycardia in patients with previous atrial surgery. BACKGROUND: Intraatrial reentrant tachycardias, a common late complication of atrial surgery, are often refractory to standard medical management. Data from experimental animals and from humans indicate that anatomic barriers resulting from residual atrial scars provide a substrate for intraatrial reentry. We speculated that these tachycardias require a narrow isthmus of tissue between surgical scars and native nonconductive boundaries and that transection of this isthmus with radiofrequency ablation would therefore constitute an effective treatment. METHODS: Fourteen patients with a history of atrial surgery and clinical intraatrial reentrant tachycardia underwent electrophysiologic testing. From activation mapping, putative surgical scars and patches that served as boundaries of reentrant circuits were identified. Radiofrequency lesions were then placed to transect the narrowest isthmus of conducting tissue between a surgical scar and an anatomic barrier. Catheter ablation was attempted only for tachycardias consistent with the patient's clinical arrhythmias. RESULTS: Radiofrequency catheter ablation was attempted for 17 (55%) of 31 tachycardias identified; it successfully terminated tachycardias in 13 (93%) of 14 patients (95% confidence interval [CI] 79% to 99%). There were clinical recurrences in six patients (46%, 95% CI 19% to 73%), each of whom underwent a repeat ablation that was successful. Twelve (86%) of 14 patients (95% CI 67% to 99%) have remained free of intraatrial reentrant tachycardia for a mean of 7.5 +/- 5.3 months. CONCLUSIONS: Anatomically guided radiofrequency catheter ablation is an effective technique for definitive management of intraatrial reentrant tachycardia in patients with previous atrial surgery.

Characterization and surgical ablation of atrial flutter after the classic Fontan repair.

BACKGROUND: Atrial flutter (AFL) is a frequent postoperative complication of the classic Fontan operation, which uses an atriopulmonary connection. We hypothesized that the suture lines alone, in the absence of any hemodynamic alterations, provide the necessary electrophysiologic substrates for AFL. The objectives of this study were to determine if the Fontan suture lines alone are sufficient to permit sustained AFL in an acute canine model and to characterize any resulting reentrant circuits to surgically ablate the AFL. METHODS: After cardiopulmonary bypass, adult dogs (n = 18) underwent a simulated classic Fontan operation. This included a longitudinal right atriotomy and an incision from the base of the right atrial appendage toward the dome of the left atrium, representing the atriopulmonary connection. In 6 of 18 dogs, an atrial septal defect was created at the level of the fossa ovalis. Unipolar 253-point biatrial endocardial mapping electrodes were placed via bilateral ventriculotomies. Induction of AFL was attempted by atrial burst pacing. If AFL could not be induced, isoproterenol was administered and pacing repeated. Activation sequence maps of the pathways of atrial reentry were generated. In 8 dogs with inducible AFL, an incision was made from the atriotomy to the atriopulmonary connection and burst pacing repeated. RESULTS: Sustained AFL could not be induced after bypass alone in any case. After the simulated Fontan operation, sustained AFL was reproducibly induced in all 18 dogs, 6 of which required isoproterenol. The mean cycle length of all cases was 177 +/- 20 ms. During AFL, atrial activation sequence maps demonstrated lines of conduction block created by both the atriotomy and the atriopulmonary connection. The isthmus of tissue between these two lines of block was essential for propagation of the reentrant wavefront. Interruption of this isthmus with an incision successfully terminated AFL in 8 of 8 dogs. CONCLUSIONS: In an acute canine model, the Fontan suture lines alone, in the absence of atrial hypertension or stretch, permit the induction of AFL. An essential electrophysiologic substrate is an isthmus of myocardium between the atriotomy and the atriopulmonary connection. Interruption of conduction through this isthmus terminates the AFL in this model and suggests a technique for ablation of AFL in patients who have undergone a classic Fontan operation.

Lateral tunnel suture line variation reduces atrial flutter after the modified Fontan operation.

BACKGROUND: Atrial flutter (AFL) is a common postoperative sequela of the modified Fontan operation, or total cavopulmonary connection. We hypothesized that injury to the crista terminalis (CT) by the lateral tunnel suture line contributes to the development of AFL in this setting. This study was designed to determine the effects of alteration of the lateral tunnel suture line, relative to the CT, on the inducibility of AFL in an acute canine model of the modified Fontan operation. METHODS: Adult mongrel dogs (n = 25) underwent a median sternotomy and normothermic cardiopulmonary bypass. In groups 1, 2, and 3, through a right atriotomy, a suture line was placed to simulate the lateral tunnel of the modified Fontan operation (n = 20). The lateral aspect of the suture line ran along the CT in group (n = 10), 5 mm medial to the CT in group 2 (n = 5), and 10 mm anterior to the CT, incorporated into the atriotomy closure, in group 3 (n = 5). In group 4 (n = 5), only the lateral portion of the suture line, along the CT, was placed. Form-fitting 253-point unipolar endocardial mapping electrodes were inserted in the left and right atria via bilateral ventriculotomies. Induction of AFL was then attempted using atrial burst pacing. If sustained AFL could not be induced, isoproterenol was administered and the pacing protocol repeated. Endocardial activation sequence maps of spontaneous rhythm and AFT were constructed. RESULTS: Under baseline conditions, after placement of the suture line, sustained AFL could reproducibly be induced in 8/10 dogs in group 1, 0/5 dogs in group 2, 0/5 dogs in group 3, and 5/5 dogs in group 4 (p < 0.001). After isoproterenol administration, sustained AFL was reproducibly inducible in the remaining 2 dogs in group 1, 4/5 dogs in group 2, and 0/5 dogs in group 3 (p = 0.01). The mean cycle length of AFL was 189 +/- 25 ms in group 1, 136 +/- 8 ms in group 2, and 182 +/- 20 ms in group 4 (p < 0.001). Atrial activation sequence maps, during sinus rhythm, demonstrated a line of conduction block along the lateral portion of the suture line in all cases in groups 1 and 4 and in only those cases in group 2 in which sustained AFL was inducible. During AFL this block facilitated unidirectional conduction, permitting propagation of the reentrant wavefront. Mean conduction velocity along the CT during sinus rhythm was 0.63 +/- 0.10 m/s in group 1, 1.04 +/- 0.17 m/s in group 2, 1.01 +/- 0.12 m/s in group 3, and 0.44 +/- 0.13 m/s in group 4 (p < 0.01). CONCLUSIONS: In an acute canine model of the modified Fontan operation, conduction block imposed by the lateral tunnel suture line is an essential component of the AFL circuit. The inducibility of AFL is increased by suture line placement along the CT. Slow conduction, resulting from injury to the CT, promotes this increased inducibility. Avoidance of the CT may reduce the incidence of AFL in children undergoing the modified Fontan operation.

Recognition and management of nonpenetrating cardiac trauma in children.

OBJECTIVE: To characterize the evaluation and clinical course of children with nonpenetrating injury to the heart. METHODS: We reviewed the medical records for children admitted to St. Louis Children's Hospital between the years 1987 to 1992 with traumatic cardiac injury. Patients with penetrating trauma were excluded; eight children, ages 4 to 13 years, were the study subjects. Chest x-ray studies, electrocardiograms, and serum creatine kinase values were obtained on admission. Two-dimensional echocardiography was performed when indicated by unexplained hemodynamic instability or abnormal radiographic findings. RESULTS: All children with nonpenetrating cardiac trauma were involved in a motor vehicle accident. The principal cardiac diagnoses were ventricular septal defect (1), mitral regurgitation (1), pericardial effusion (2), contusion (3), and arrhythmia (1). Multisystem injury was present in each case, but cardiac injury was not suspected at the time of admission in seven of the eight patients. The hemodynamic status of four children was compromised 12 to 48 hours after admission; echocardiography was diagnostic in each instance, but the electrocardiogram and creatine kinase values were nonspecific. Two patients eventually required cardiac surgery. CONCLUSIONS: Recognition of blunt cardiac trauma in children may be confounded by associated multisystem injury and the delayed onset of clinical manifestations. Echocardiography is a sensitive diagnostic tool for hemodynamically significant disease, and should be performed promptly when patients have unexplained hypotension or diminished peripheral perfusion.

Origin of the sinus impulse.

It was generally accepted that the site of normal impulse origin within the atria was a single static focus within the sinus node. This review will examine how this model of impulse origin came about and has evolved. Early on, conflicting data suggested that the sinus node focus was not static and changed with interventions that changed heart rate, such as vagal stimulation. Furthermore, even with removal of the sinus node, a normal atrial rhythm was generated. High-resolution mapping in humans and dogs showed that the initiation of the impulse was dynamic and could be multicentric, with more than one focus initiating a single beat. Shifts in the site of origin correlated with changes in rate and were consistent with P wave changes routinely observed in the standard ECG. These studies suggested multiple pacemakers were responsible for impulse initiation. However, it was not clear how these widespread pacemakers were coordinated to function synchronously. Recent canine data suggest that the node may be partially insulated from the surrounding atrium, resulting in multicentric origin starting from a single site within the node. What has evolved is a model of impulse origin with a sinus node having discrete exit sites and a dominant pacemaker within the node that can shift to other nodal sites. Complex and changing conduction out of the node, coupled with extranodal pacemakers, which can assume dominance over the node, combine with the autonomic nervous system to control heart rate and the pattern of impulse origin within the atria.

Atrial flutter after lateral tunnel construction in the modified Fontan operation: a canine model.

Intraatrial reentrant tachycardia, or atrial flutter, is a common postoperative problem after Fontan repair, which involves an atriopulmonary connection. A modification of Fontan repair, total cavopulmonary connection, minimizes the portion of the right atrium exposed to stretch and hypertension; however, atrial flutter continues to occur after this procedure. We postulated that the intraatrial lateral tunnel suture line of total cavopulmonary connection, in the absence of physiologic alterations such as atrial hypertension or stretch, provides the necessary electrophysiologic substrate for atrial flutter. The purpose of this study was to produce a canine model of total cavopulmonary connection (1) to establish that the intraatrial suture line alone is sufficient to permit sustained atrial flutter and (2) to characterize the pathways of resulting reentrant arrhythmias. After induction of general anesthesia, 25 to 30 kg dogs (n = 17) underwent median sternotomy, cradling of the pericardium, and placement of a pacing electrode on the right atrial appendage. Normothermic cardiopulmonary bypass was initiated. The total cavopulmonary connection suture line was placed through a standard right atriotomy,simulating construcion of the lateral tunnel. After closure of the atriotomy, 253 point unipolar atrial endocardial form-fitting electrodes were placed through bilateral ventriculotomies. By means of atrial burst pacing and programmed extrastimulation, induction of atrial flutter was attempted. If atrial flutter could not be induced, isoproterenol was infused and the stimulation protocol was repeated. After induction of atrial flutter, mapping of the activation sequence was performed. Before suture line placement, no dog had inducible atrial flutter. After placement of the suture line, sustained atrial flutter was reproducibly induced in every dog, although isoproterenol was required for this in three (17.6%). The mean flutter cycle length was 177 +/- 30 msec. In each case, the atrial flutter circuit was limited to the right atrium, with the left atrium being passively activated. The atrial flutter circuit was dependent on a corridor of myocardium that resulted from conduction block on the free wall, created by the lateral margin of the total cavopulmonary connection. In no case was the atriotomy integral to the atrial flutter circuit. This study establishes that the total cavopulmonary connection baffle suture line alone, without alteration in circulatory physiology, creates a sufficient anatomic substrate for atrial flutter in a short-term canine model. Delineation of the anatomic boundaries of the reentrant circuit raises the possibility of targeting areas within the circuit that could be modified, potentially reducing the incidence of postoperative atrial flutter after total cavopulmonary connection.

Impact of clinical history and electrophysiologic characterization of accessory pathways on management strategies to reduce sudden death among children with Wolff-Parkinson-White syndrome.

OBJECTIVES: This study sought to determine whether the clinical and electrophysiologic criteria developed in adults also identify children with Wolff-Parkinson-White syndrome at risk for sudden death. BACKGROUND: In adults with Wolff-Parkinson-White syndrome, a shortest RR interval <220 ms during atrial fibrillation is a sensitive marker for sudden death. However, because reliance on the shortest RR interval has a low positive predictive value, the clinical history has assumed a pivotal role in assessing risk. This approach has not been evaluated in children. METHODS: We retrospectively evaluated 60 children

Relative densities of muscarinic cholinergic and beta-adrenergic receptors in the canine sinoatrial node and their relation to sites of pacemaker activity.

The site of earliest extracellular electrical activation in the sinoatrial node (SAN) is known to shift in response to autonomic stimuli, but the mechanisms underlying this phenomenon and the determinants of the location of dominant pacemaker activity have not been elucidated. The present study was designed to characterize the spatial distribution of muscarinic cholinergic and beta-adrenergic receptors in the canine SAN and to determine whether a consistent relationship exists between autonomic receptor densities and the site of dominant pacemaker activity. We used quantitative light-microscopic autoradiography of radioligand binding sites to characterize the spatial distribution of muscarinic cholinergic and beta-adrenergic receptor subtypes in tissue sections containing the SAN and adjacent right atrial muscle from 18 canine hearts. Muscarinic receptor density was 5.4 times greater in SAN cells than in atrial myocytes (P < .01). Total beta-adrenergic receptor density was more than 3 times greater in SAN cells than in atrial myocytes (P < .0001), due entirely to the significantly greater number of beta 1-adrenergic receptors in the SAN. The region of dominant pacemaker activity, localized in 4 hearts with in vitro mapping, consistently exhibited greater densities of muscarinic and beta 1-adrenergic receptors than other SAN regions. Muscarinic receptor density in the dominant pacemaker region was 18 +/- 2% and 29 +/- 7% higher than in adjacent superior and inferior regions, respectively. beta 1-Receptor density in the dominant site was 53 +/- 5% and 26 +/- 4% higher than in adjacent superior and inferior SAN regions, respectively. Thus, the SAN is richly endowed with both muscarinic cholinergic and beta 1-adrenergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary negativity does not predict dominant pacemaker location: implications for sinoatrial conduction.

Activation sequence maps derived during normal sinus rhythm from extracellular potentials in the canine right atrium exhibit widely separated sites of origin. The objectives of this study were to characterize the distribution of pacemakers within the right atrium and to determine the relationship of pacemaker action potentials to sites of earliest surface activation as well as to local extracellular electrograms. The right atria of six adult mongrel dogs were rapidly excised under deep pentobarbital sodium anesthesia and perfused with 95% O2-5% CO2 Krebs-Henseleit solution. Action potentials from the epicardial surface were recorded throughout the region bounded by the crista terminalis laterally and the atrial septum medially. Simultaneously, unipolar extracellular electrograms were recorded from 250 endocardial sites. The earliest pacemakers preceded the earliest electrogram by 63 +/- 34 ms; the latest pacemakers followed the earliest electrogram by 71 +/- 40 ms. Primary negativity in the extracellular electro gram did not predict the site of the earliest or dominant pace maker and in some cases was associated with the latest pace makers. We conclude that primary negativity and/or the sites of earliest activation reflect the point at which the impulse engages atrial myocardium, not the site of earliest pacemaker activity. As such, early extracellular activation appears to represent sites of exit from a relatively insulated sinus node.

Randomized comparison of atenolol and fludrocortisone acetate in the treatment of pediatric neurally mediated syncope.

Overall, these results indicate that oral treatment of neurally mediated syncope is safe and efficacious. Further randomized trials in children will be required to determine the significance of a placebo effect, as well as potential differences in results related to the mechanism of syncope.

Simultaneous epicardial and endocardial activation sequence mapping in the isolated canine right atrium.

BACKGROUND: Since the atria are thin-walled structures, most studies that have examined the spread of activation in the atria have assumed that they behave electrophysiologically as a two-dimensional surface. It was the objective of this study to determine whether or not this assumption is true by simultaneously mapping the epicardial and endocardial activation sequences in the right atrium. METHODS AND RESULTS: Identical precisely superpositioned epicardial and endocardial electrode templates with 250 unipolar electrodes each were used to map the isolated canine right atrium (n = 8) during continuous perfusion and superfusion with Krebs-Henseleit buffer. Data were recorded during control conditions (normal sinus rhythm), continuous pacing (S1S1 = 300 msec), and premature stimulation (S1S2 = effective refractory period + 5 msec). Pacing was performed at two sites, one located on the inferior crista terminalis and one lateral to the crista terminalis on a pectinate muscle. Tachyarrhythmias were induced by a single extrastimulus during the continuous perfusion of acetylcholine (10(-3.5) mol/L). Individual electrode sites were correlated with the gross anatomy and histology. Activation time differences were calculated between each two corresponding epicardial and endocardial sites. There were differences in the activation times between the epicardium and endocardium during all experimental conditions. However, the average difference for each condition was < 1 msec, suggesting that overall activation did not spread faster on either the epicardium or the endocardium, even though in certain regions one surface could lead the other. The dispersion of time differences was smallest during normal sinus rhythm and continuous pacing (SD = 5.6-5.8 msec) and largest after premature stimulation (SD = 6.3 msec for crista pacing, p < 0.05; SD = 8.1 msec for pacing lateral to the crista, p < 0.001). Differences in the activation sequence correlated with the underlying anatomic architecture. The largest differences in activation times between the epicardium and endocardium were associated with those regions of the atrium where pectinate muscles ran below the epicardial surface. The pectinate muscles in those areas were often discontinuous with the epicardial surface and facilitated the discordant epicardial-endocardial activation. The discordant activation was also found in regions where the atrial wall thickness was < 0.5 mm and correlated with transmural differences in fiber orientation. A tachyarrhythmia induced in the presence of acetylcholine, which demonstrated a focal activation pattern, was shown to have a reentrant loop that used free-running muscle bundles connecting the epicardial and endocardial surfaces, resulting in a three-dimensional pathway. CONCLUSIONS: The findings of this study demonstrate that epicardial and endocardial activation can be discordant in specific regions and that discordance increases with abnormal activation sequences. Many of the differences in the epicardial and endocardial activation can be correlated with the heterogeneity of the anatomic architecture of the right atrium. The study also demonstrates that reentry can occur in a three-dimensional plane using the epicardial and endocardial surfaces connected by transmural muscle fibers.

Cholinergically mediated tachyarrhythmias induced by a single extrastimulus in the isolated canine right atrium.

Cholinergic agonists and vagal stimulation potentiate the inducibility of atrial fibrillation. To describe the activation patterns and determine the mechanisms that sustain cholinergic fibrillation, tachyarrhythmias were induced with a single extrastimulus in the isolated Krebs-Henseleit-perfused canine right atrium (n = 11) at increasing concentrations of acetylcholine (from 10(-7.5) to 10(-4.5) M). Bipolar electrograms were recorded from 250 epicardial sites simultaneously during control conditions and during extrastimulation (S1S1, 300 msec; S1S2, effective refractory period+5 msec) with and without acetylcholine. Activation sequence maps were constructed from each recording. Without acetylcholine, no tachyarrhythmias were induced. With increasing concentrations of acetylcholine, the refractory period decreased, and nonsustained (< 2 seconds) rapid repetitive responses were induced. At higher concentrations, a sustained (> 2-minute) fibrillation was induced. Activation sequence maps revealed that the rapid repetitive responses were characterized by multiple reentrant circuits. The number of circuits and wavelets increased in a dose-dependent fashion. However, unexpectedly, this trend did not continue when the tachyarrhythmia became sustained. Instead, the reentry tended to stabilize to a small, single, relatively stable reentrant circuit. In conclusion, the data suggest that, in this model, below a critical level of refractory period (< 95 msec) atrial reentrant circuits, unassociated with anatomic obstacles, can become stable and dominate activation.

Spontaneous tachyarrhythmias after cholinergic suppression in the isolated perfused canine right atrium.

Atrial fibrillation occurs spontaneously after bradycardia induced by acetylcholine infusion or vagal stimulation. To determine the mechanism of initiation of this tachyarrhythmia, we infused acetylcholine (5 ml, 10(-3.5) M) into Krebs-Henseleit-perfused isolated canine right atria (n = 10). Unipolar electrograms were recorded from 250 sites simultaneously during control rhythms, pacing (cycle length = 300 msec) with and without acetylcholine, and recovery of spontaneous activity. Activation sequence maps were constructed from each recording. Stable spontaneous rhythm was present in all preparations during control conditions. Activation sequence maps, recorded during continuous pacing with and without acetylcholine, demonstrated no dromotropic changes due to the acetylcholine. Focal asynchronous recovery of spontaneous activity was initiated from different sites, resulting in bigeminal or trigeminal premature depolarizations in 41 of 73 cases after infusion of acetylcholine. A reentrant tachyarrhythmia was initiated in 24 of 41 cases by the closely coupled recovery beats (A1A2 = 100 +/- 37 msec; A2A3 = 97 +/- 27 msec). The reentry was initiated by interaction of the premature impulse with regions of functional block that were a result of the cholinergically induced dispersion of refractoriness. All the tachyarrhythmias terminated spontaneously, and stable spontaneous control rhythms returned. In conclusion, the data suggest that the premature depolarizations that initiate the reentrant tachyarrhythmia are caused by the asynchronous recovery of multiple right atrial pacemakers accompanied by variable entrance block at the later depolarizing sites.