Morphological and membrane characteristics of spider and spindle cells isolated from rabbit sinus node.

This study reports the comparative quantitative, morphological, and electrophysiological properties of two pacemaker cell types, spider and spindle-shaped cells, isolated from the rabbit sinoatrial node. Isolated nodal cells were studied with perforated and ruptured patch whole cell recording techniques. The basic spontaneous cycle length of the spider cells was 381 +/- 12 ms, and the basic spontaneous cycle length of the spindle cells was 456 +/- 17 ms (n = 12, P < 0.05). The spider cells had a more positive maximum diastolic potential (-54 +/- 1 mV) compared with the spindle cells (-68 +/- 1mV, P < 0.05). The overshoot and action potential amplitudes were also smaller in the spider cells. The hyperpolarization-activated inward (I(f)) current density, measured from their tail currents, was 15 +/- 1.3 pA/pF for the spider cells and 9 +/- 0.7 pA/pF for the spindle cells (P < 0.01). I(f) current activation voltage was more positive in the spider cells than the spindle cells. Isoproterenol (1 microM) decreased the spontaneous cycle length of the spider cells by 28 +/- 3% and the spindle cells by 20 +/- 1.5% (P < 0.05). Acetylcholine (0.5 microM) hyperpolarized the membrane potential of the spider cells to -86 +/- 0.7 mV and the spindle cells to -76 +/- 0.8 mV (P < 0.05). In summary, there are at least two distinct pacemaker cell types in the sinus node with different electrophysiological characteristics.

Cryoablation of ventricular tachycardia guided by return cycle mapping after entrainment.

BACKGROUND: Although the implantable cardioverter-defibrillator effectively prevents sudden cardiac death, patients are still prone to recurrence of ventricular tachyarrhythmias. Electrophysiologically guided surgery is the most effective modality in abolishing ventricular tachycardia, having a lower recurrence rate than pharmacologic therapy or catheter ablation. Return cycle mapping after entrainment has been shown to localize the central common pathway, which is the target region for ablation, without pacing at the pathway or recording the potentials from the pathway. METHODS: To determine the accuracy and usefulness of return cycle mapping in surgery for ventricular tachycardia, we cryoablated 8 morphologies of ventricular tachycardia induced in postinfarction dogs with the guidance of return cycle mapping. The ventricular tachycardia was entrained from 3 to 5 different epicardial sites at a paced cycle length 10 to 20 ms shorter than the ventricular tachycardia cycle length and the epicardium was mapped with 61 unipolar electrodes during cessation of entrainment to construct return cycle maps. The return cycle was determined by subtracting the first activation time from the second activation time after the last stimulus in each electrode location, and the maps were then displayed on a computer. RESULTS: The total analysis process was completed within 3 minutes by means of a computer with custom-made programs. The activation map during ventricular tachycardia did not localize the central common pathway in any morphology of ventricular tachycardia, because the pattern of activation was concentric and diastolic potentials were not recorded. Cryoablation of the region where the isotemporal lines of the return cycle equal to the ventricular tachycardia cycle length intersected resulted in termination of ventricular tachycardia in all morphologies. The intersection was 26 +/- 9 mm from the earliest activation site. Epicardial mapping with 253 electrodes during cryothermia showed that the region localized by return cycle mapping was the central common pathway sandwiched between the lines of conduction block and that the cryolesion connected the lines of block, blocked the rotating wave front, and resulted in termination of the ventricular tachycardia. CONCLUSION: Return cycle mapping provides an accurate and rapid means of localizing the central common pathway without the need for recording potentials from the pathway or pacing at the pathway in ablation for ventricular tachycardia.

Spatial distribution and frequency dependence of arrhythmogenic vagal effects in canine atria.

INTRODUCTION: Prior studies in isolated canine atria demonstrated that acetylcholine-induced reentrant atrial fibrillation (AF) was triggered by multifocal activity in the area of normal impulse origin (sinus node-crista terminalis). The aim of this study was to investigate the activation sequence in AF induced by vagal stimulation (VS) in intact dog hearts. METHODS AND RESULTS: VS (10 to 50 Hz, 1 msec, 15 V, 5-sec trains) induced single or multiple atrial premature depolarizations (APDs), and/or AF in 8 of 10 open chest dogs. Occurrence of APDs and AF increased with increasing VS intensity. Epicardial mapping (254 unipolar electrodes) of both atria showed that APDs as a rule emerged from ectopic sites, often from the right atrial appendage. Activation mapping of the first 10 cycles of AF showed that only a small number (<3 to 4) of unstable reentrant circuits were possible at the same moment. Moreover, most sustained VS-induced AFs were accounted for by a single leading stable reentrant circuit that activated the remainder of the atria. CONCLUSION: (1) Occurrence of vagally induced APDs and AF increases with increasing frequency of VS. (2) VS-induced focal ectopic APDs are widely distributed over the atria. (3) A single APD can be sufficient for initiation of reentrant AF. (4) Despite its high rate of sustained AF, it may be maintained by single stable reentrant circuit. (5) The atrial septum can play an important role in both the initiation and the maintenance of VS-induced AF.

The development of the Maze procedure for the treatment of atrial fibrillation.

The Maze procedure was developed for the treatment of atrial fibrillation over a period of several years. Extensive experimental and clinical studies of the underlying electrophysiology of the arrhythmia were performed, and numerous surgical techniques and principles were tried before the Maze procedure was conceived. Few cardiac surgical procedures have undergone more extensive research and experimental trials before being applied clinically. This article gives a brief summary of the work leading up to the eventual Maze-III procedure that is now in clinical use.

The closed heart MAZE: a nonbypass surgical technique.

BACKGROUND: The MAZE-III is the surgical treatment of choice for medically refractory atrial fibrillation. Although a number of nonsurgical techniques are evolving to duplicate the transmural atrial lesions of the MAZE-III, the surgical atriotomy remains the gold standard for conduction block. It was the objective of this study to surgically create the atrial incisions of the MAZE-III without the use of cardiopulmonary bypass. METHODS: A technique was developed to create and intersect the linear incisions of the MAZE-III on 10 beating canine hearts without the use of cardiopulmonary bypass using a "tunnel" of atrial tissue. The effectiveness of the procedure was tested by atrial burst pacing. RESULTS: This technique was successfully performed on 10 mongrel dogs without operative mortality. Preoperatively, sustained atrial fibrillation (>30 seconds) was induced in all animals. Postoperatively, all the animals remained in sinus rhythm even after burst pacing. CONCLUSIONS: In an experimental canine model, the MAZE-III can be performed on beating hearts without the assistance of cardiopulmonary bypass using a "tunnel" technique. This technique allows for the immediate assessment of electrophysiologic and mechanical function after the MAZE-III, or any other type of procedure using the "maze principle" and may find future application in the clinical arena.

Radial approach: a new concept in surgical treatment for atrial fibrillation I. Concept, anatomic and physiologic bases and development of a procedure.

BACKGROUND: The maze procedure cures atrial fibrillation; however, it isolates the pulmonary vein area and results in discordant activation in certain adjacent left atrial segments, which affects left atrial function. To preserve a more physiologic atrial transport function, we developed a new concept of surgical treatment for atrial fibrillation-the radial approach. The atrial incisions radiate from the sinus node toward the atrioventricular annular margins to allow a more physiologic atrial activation sequence and parallel the atrial coronary arteries to preserve blood supply to most atrial segments. METHODS: We examined the atrial coronary arteries and the activation sequence during sinus rhythm in normal canine hearts to design the atrial incisions according to the concept of a radial approach. RESULTS: The pattern of coronary artery distribution was centripetal, branching from the right coronary or left circumflex coronary artery at the right or left atrioventricular groove and spreading toward the sinus node. The endocardial mapping of the atria disclosed some important findings in designing the atrial incisions of the radial approach: the activation sequence at the left atrial septum and at the posterior left atrium between the pulmonary vein orifices. The atrial incisions were designed according to these findings. CONCLUSIONS: The radial approach may represent a more physiologic atrial transport function.

Radial approach: a new concept in surgical treatment for atrial fibrillation. II. Electrophysiologic effects and atrial contribution to ventricular filling.

BACKGROUND: In a previous study the atrial incisions that follow the concept of the radial approach were designed according to the activation sequence during sinus rhythm and the atrial coronary artery anatomy in normal dogs. The purpose of the present study was to determine whether the radial approach provides a more physiologic activation sequence and atrial transport function than the maze procedure. METHODS: Ten dogs that had undergone the radial approach (n = 5) or the maze procedure (n = 5) were studied 6 weeks postoperatively. Sinus node function and inducibility of atrial fibrillation were examined before and after operation. The atria were mapped endocardially with 212 electrodes, and atrial activation sequences during sinus rhythm and right atrial pacing were examined. Atrial transport function was assessed by transepicardial Doppler echocardiography. RESULTS: No dogs developed sinus node dysfunction postoperatively. Both the radial approach and the maze procedure equally prevented sustained atrial fibrillation. The atrial activation sequence was more synchronous after the radial approach than after the maze procedure. There was no electrically isolated region after the radial approach. The total activation time of the left atrium was significantly shorter after the radial approach than after the maze procedure (53.6+/-9.8 versus 70.5+/-9.6 ms, p<0.05). The ratio of peak flow velocity of the E wave to the A wave (peak E/A) of the transmitral Doppler flow was significantly smaller after the radial approach than after the maze procedure (1.7+/-0.4 versus 3.5+/-1.7, p<0.05). The atrial filling fraction of the transmitral Doppler flow was significantly larger after the radial approach than after the maze procedure (29.9%+/-7.3% versus 14.8%+/-5.0%, p<0.01). There was no significant difference in peak E/A and atrial filling fraction of the transtricuspid Doppler flow between the two procedures. CONCLUSIONS: The radial approach provides a more synchronous activation sequence and atrial transport function, and thus may represent a more physiologic alternative to the maze procedure as a surgical treatment for atrial fibrillation.

[Effects of warm blood and clot crystalloid cardioplegia on the heart rate variability of canine].

The objectives of this study were to explore the mechanisms of cardiac autonomic system (CAS) impairment and to assess whether warm blood cardioplegia can prevent the decrease of heart rate variability (HRV) after CPB. Twelve adult mongrel dogs were divided into two groups. One group received warm blood cardioplegia and maintained at a systemic temperature of 38 degrees C throughout the experiment (WB group). The other received cold crystalloid cardioplegia at 31 degrees C and topical hypothermia (CC group). Anesthesia was induced and maintained with sodium pentobarbital and isoflurane. The heart was exposed through a right thorectomy. CPB was established using a single right atrial cannula. The arterial cannula was placed in the right femoral artery. The crossclamp time for both groups was 30 minutes. Serum potassium levels were normalized throughout the study. Each animal's ECG was continuously recorded for 24 hours before surgery and for the first five postoperative days (POD) using a two-channel Holter monitor. The data were analyzed for heart rate variability (TP = total power, 0.01-1.00; LF = low frequency, 0.04-0.15; HF = high frequency, 0.15-0.40; LF/HF). There were no differences in the preoperative values. In both groups the TP, LF, and HF decreased, compared to control (P < 0.05), with CC group having significantly lower TP, LF and HF than the WB group (P < 0.05). The LF/HF did not change both between groups and between before- and after-CPB in each group (P > 0.05). The mean heart rate at 24 hours (MHR) increased in both groups, compared to control (P < 0.05), with CC group having a significantly higher MHR than WB group (P < 0.05). The data suggest that CPB, with warm blood or cold crystalloid cardioplegia does not disturb the balance of CAS, but it causes the decrease of HRV, and warm blood cardioplegia can not prevent the impairment of HRV.

Varying types of circus movement re-entry with both normal and dissociated contralateral conduction causing different right and left atrial rhythms in canine atrial flutter.

The purpose of this study was to develop an animal model of atrial flutter (AFL) or fibrillation (AFB) and to determine precisely the pathway of atrial activation during arrhythmias induced by programmed stimulation. In 10 dogs, a shunt from the left subclavian artery to the left upper pulmonary vein was created to produce left atrial enlargement. Five months later, using programmed electrical stimulation, it was possible to induce 17 sustained atrial tachycardias in 9 of the 10 dogs, including 9 episodes of AFL caused by circus movement re-entry, 6 episodes of focal tachycardia, and 2 episodes of AFB. Short cycle length left atrial tachycardias caused by either circus movement or a focus did not propagate in a uniform 1:1 pattern to the right atrium (RA), resulting in RA dissociation. In these arrhythmias, complex wavefronts from both current and preceding left atrial cycles coexisted in the RA. Circus movement was associated with a spectrum of different re-entrant pathways with different path lengths. These differences in the path length were determined by various ways in which obstacles such as the superior vena cava and orifice of the right atrial appendage or pulmonary vein orifices were combined by contiguous areas of functional block.

Return cycle mapping after entrainment of ventricular tachycardia.

BACKGROUND: The central common pathway, which is the target for ablation in reentrant ventricular tachycardia, can be localized by entrainment mapping techniques. However, localization of the pathway is not always possible because of the elevated pacing threshold and the low voltage and fractionated potentials at the pathway. We examined whether return cycle mapping after entrainment localizes the pathway without pacing at the pathway or recording the potentials from the pathway and determined the required electrode resolution to localize the pathway. METHODS AND RESULTS: Epicardial mapping was performed with 253 unipolar electrodes during and after entrainment of 13 morphologies of ventricular tachycardia that were induced in dogs 4 days after infarction. The return cycle was calculated by subtracting the first activation time from the second activation time after the last stimulus and the return cycle distribution map was constructed for each stimulation site. The return cycle isochrones equal to the ventricular tachycardia cycle length converged on the lines of conduction block irrespective of the stimulation site, and the central common pathway was localized at the region between the intersections of the return cycle isochrones after entrainment from different stimulation sites. The potentials from the central common pathway were not required to localize the pathway, and the mapping accuracy did not change with or without analysis of the potentials from the pathway. According to the correlation between the electrode resolution and the mapping accuracy, an interelectrode distance of 8.5 mm was estimated as sufficient resolution for successful tachycardia termination during radiofrequency ablation guided by return cycle mapping. CONCLUSIONS: Return cycle mapping after entrainment localizes the central common pathway without pacing at the pathway or recording the potentials from the pathway. This new mapping technique could improve the success rate of the ablative procedures.

Differential expression of gap junction proteins in the canine sinus node.

Electrical coupling of pacemaker cells at gap junctions appears to play an important role in sinus node function. Although the major cardiac gap junction protein, connexin43 (Cx43), is expressed abundantly in atrial and ventricular muscle, its expression in the sinus node has been a subject of controversy. The objectives of the present study were to determine whether Cx43 is expressed by sinus node myocytes, to characterize the spectrum of connexin expression phenotypes in sinus node pacemaker cells, and to define the spatial distribution of different connexin phenotypes in the intact sinus node. To fulfill these objectives, we performed high-resolution immunohistochemical analysis of disaggregated adult canine sinus node preparations. Using enhanced tissue preservation and antigen retrieval techniques, we also performed immunohistochemical studies on sections of intact canine sinus node tissue. Analysis of disaggregated sinus node preparations revealed three populations of pacemaker cells distinguished on the basis of connexin immunohistochemical phenotype: approximately 55% of cells expressed only connexin40 (Cx40); 30% to 35% of cells expressed Cx43, connexin45 (Cx45), and Cx40; and the remaining cells had no detectable connexin expression. In immunostained sections of intact sinus node, Cx43- and Cx45-positive cells were limited in their distribution and were observed in discrete bundles that appeared to abut atrial myocytes. In contrast, Cx40 immunoreactive signal was widely distributed in the sinus node region. These results indicate that subsets of pacemaker cells express distinct connexin phenotypes. Differential expression of connexins could create regions within the sinus node with different conduction properties, thereby contributing to the nonuniform conduction properties seen in this tissue.

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.

Global electrophysiological mapping of the atrium: computerized three-dimensional mapping system.

The atria are anatomically complex three-dimensional (3-D) structures. Impulse propagation is dynamic and complex during both normal conduction and arrhythmia. Atria activation has traditionally been represented on two-dimensional surface maps, which have inherent inaccuracies and are difficult to interpret. Interactive computerized 3-D display facilitates interpretation of complex atrial activation sequence data obtained from form-fitting multipoint electrodes. Accordingly, the purpose of this article is to describe the application of 3-D form-fitting electrode molds to the 3-D mapping and display system developed in this laboratory for the study of complex cardiac arrhythmias. Computer generated 3-D surface models are created from a database of serial cross-sectional anatomical images. Points chosen on endocardial and epicardial surfaces in each cross-sectional image are processed to create polygons defining myocardial wall boundaries. The polygons from adjacent serial images are then combined, to create a 3-D surface model. The discrete anatomical locations of unit electrodes on multipoint electrode templates are then assigned in the proper position on the surface model. Computer analysis of simultaneous activation data from each unit electrode is performed based on parameters set by the user. Activation data from each unit electrode site are displayed on the computer surface model in a color spectrum correlating with a user-defined time scale. Activation sequence maps can be visualized as static isochrone maps, interval maps, or as dynamic maps at variable speeds, from any 3-D perspective. Thus, an interactive computerized 3-D display system is described, which allows anatomically superior analysis and interpretation of complex atrial arrhythmias.

[Multielectrode mapping study of proarrhythmic vagal effects in the dog atria]. / Issledovanie metodom mnogokanal'nogo kartirovaniia aritmogennogo deistviia bluzhdaiushchikh nervov v predserdiiakh sobaki.

Epicardial mapping (254 unipolar electrodes) of the dog heart both atria was performed to determine spatial distribution of arrhythmic events. The mapping showed that the first atrial premature depolarisation (APD) emerged from ectopic foci, it showed also specific multifocal patterns suggesting a septal source of tachycardia. The data obtained suggests that vagal stimulation (VS) induces focal ectopic APDs, that APDs and escape beats may be due to the same mechanism of spontaneous depolarization in the absence of a reset from dominant rhythm, that a single VS-induced APD is sufficient for initiation of a reentrant atrial fibrillation.

Microfibrosis produces electrical load variations due to loss of side-to-side cell connections: a major mechanism of structural heart disease arrhythmias.

The purpose of this article is to demonstrate how adaptive changes in myocardial microstructure provide mechanisms for emergent new conduction disturbances that initiate reentrant arrhythmias. The mechanisms are based on discontinuous conduction phenomena produced by increases in cellular loading; these increases result from changes in the normal distribution of the gap junctions. Recent studies that at a microscopic level propagation in normal mature cardiac muscle is stochastic. For example, the nonuniform and irregular distribution of the gap junctions in such normal muscle produces load variations that are associated with changes in Vmax inside individual cells during both longitudinal and transverse propagation. The stochastic nature of normal propagation at a microscopic level offers considerable protection against arrhythmias by reestablishing the general trend of wavefront movement after small variations in excitation events occur. If such microscopic diversity is decreased, large fluctuations in load develop that are distributed over more cells than usual. The decrease in diversity may be caused by loss of side-to-side coupling between fibers, which produces relatively isolated groups of cells with microfibrosis. With loss of side-to-side fiber coupling, the myocardial architecture may fail to reestablish a smoothed wavefront at the macroscopic level. Spatial nonuniformities of electrical loading then give rise to conduction block and reentry.

Relationship between local atrial fibrillation interval and refractory period in the isolated canine atrium.

BACKGROUND: Atrial refractory periods and their spatial distribution are important determinants of atrial reentrant arrhythmias. The objective of this study was to demonstrate a correlation between the local atrial fibrillation interval (AFI) and local effective refractory period (ERP). METHODS AND RESULTS: To measure the local ERP and local AFI under stable conditions without hemodynamic, autonomic, or reflex influences, isolated perfused canine whole atria were used (n = 8). The isolated atria were mounted on two endocardial electrodes. Bipolar electrograms were simultaneously recorded from 253 endocardial sites, and 16 to 20 randomly distributed electrodes were used to measure the local ERP by the extrastimulus technique. In all studies, several episodes of AF were induced by a single extrastimulus. The ERP and minimum AFI converged with increasing duration of AF. The convergence was more rapid if the total duration of AF analyzed came from multiple episodes of AF. The correlation coefficient between the local ERP and minimum local AFI was .92 (n = 119, P < .001). The minimum AFI was used to construct AFI distribution maps at all 253 sites. Activation block during premature stimulation correlated with regions of long AFI. CONCLUSIONS: The minimum local AFI measured from at least 10 seconds of AF approximates the local ERP. Construction of a minimum local AFI map during AF can be used to predict the distribution of refractoriness and can be used to predict sites of functional block. Contrary to studies done in intact animals and patients, the AFI were longer than the ERPs, suggesting that reflex changes may shorten ERP in the intact heart.

Beta-adrenergic and muscarinic cholinergic receptor densities in the human sinoatrial node: identification of a high beta 2-adrenergic receptor density.

The objective of this study was to measure autonomic receptor densities in the human sinoatrial node and adjacent atrial myocardium to gain further insights into autonomic regulation of sinoatrial node function in the human heart. Sinoatrial nodes (n = 9) were acquired from human donors. Quantitative light microscopic autoradiography of radioligand binding sites in tissue sections was used to compare beta-adrenergic and muscarinic cholinergic receptor densities within specific tissue compartments of the sinoatrial node and adjacent myocardium. Total beta-adrenergic receptors were measured with the nonsubtype selective radioligand [125I]iodocyanopindolol. beta 2-Adrenergic receptors were determined by measuring the amount of radioactivity bound to sections incubated with radioligand in the presence of the highly beta 1-selective antagonist CGP-20712A. Specific autoradiographic grain densities were normalized to myocyte area/unit tissue area. Myocytes in the sinoatrial node occupied 47.7% +/- 0.1% of the total tissue area compared with 92.8% +/- 0.1% in myocardium (P < 0.001). Total specific beta-adrenergic receptor density per unit myocyte area was 3.5 +/- 0.9 times greater in the sinoatrial node than in myocardium (P < 0.001). The relative densities of beta 1-(4.2, P < 0.002), beta 2-(2.6, P < 0.002), and muscarinic (3.3, P < 0.001) receptors were significantly greater in the sinoatrial node than in the atrium. Thus, total beta-adrenergic and muscarinic cholinergic receptor densities are > 3-fold higher in the sinoatrial node than adjacent atrial myocardium, reflecting their specialized roles in regulating cardiac rate and rhythm. The beta 1-subtype is predominant in both regions. The beta 2-subtype, however, is > 2.5-fold more abundant in the sinoatrial node than in atrial myocardium. The relatively high beta 2-receptor density in the human sinoatrial node is consistent with physiologic studies that implicate this receptor in regulating cardiac chronotropism.

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.

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.