Large eddy simulation of powered Fontan hemodynamics.

Children born with univentricular heart disease typically must undergo three open heart surgeries within the first 2-3 years of life to eventually establish the Fontan circulation. In that case the single working ventricle pumps oxygenated blood to the body and blood returns to the lungs flowing passively through the Total Cavopulmonary Connection (TCPC) rather than being actively pumped by a subpulmonary ventricle. The TCPC is a direct surgical connection between the superior and inferior vena cava and the left and right pulmonary arteries. We have postulated that a mechanical pump inserted into this circulation providing a 3-5 mmHg pressure augmentation will reestablish bi-ventricular physiology serving as a bridge-to-recovery, bridge-to-transplant or destination therapy as a "biventricular Fontan" circulation. The Viscous Impeller Pump (VIP) has been proposed by our group as such an assist device. It is situated in the center of the 4-way TCPC intersection and spins pulling blood from the vena cavae and pushing it into the pulmonary arteries. We hypothesized that Large Eddy Simulation (LES) using high-order numerical methods are needed to capture unsteady powered and unpowered Fontan hemodynamics. Inclusion of a mechanical pump into the CFD further complicates matters due to the need to account for rotating machinery. In this study, we focus on predictions from an in-house high-order LES code (WenoHemo(TM)) for unpowered and VIP-powered idealized TCPC hemodynamics with quantitative comparisons to Stereoscopic Particle Imaging Velocimetry (SPIV) measurements. Results are presented for both instantaneous flow structures and statistical data. Simulations show good qualitative and quantitative agreement with measured data.

A prospective analysis of the incidence and risk factors associated with junctional ectopic tachycardia following surgery for congenital heart disease.

This study was designed to evaluate the incidence and risk factors associated with the occurrence of junctional ectopic tachycardia (JET) in patients after congenital heart surgery. We prospectively analyzed cardiac rhythm status in 336 consecutive patients undergoing surgery for congenital heart disease at our institution during a 1-year period. The incidence of JET was 8% (27/336). Repairs with the highest incidence of JET were arterial switch operation (3/13, 23%), atrioventricular (AV) canal repair (4/19, 21%), and Norwood repair (2/10, 20%). Compared to patients with no arrhythmias, patients with JET were more likely to be younger (2.75 +/- 2.44 vs 5.38 +/- 7.25 years, p < 0.01), have had longer cardiopulmonary bypass times (126 +/- 50 vs 85 +/- 73, p < 0.01), and have a higher inotrope score (6.26 +/- 7.55 vs 2.41 +/- 8.11, p < 0.01). By multivariate analysis, ischemic time was the only factor associated with JET [odds ratio, 1.01 (confidence interval, 1.005-1.02); p = 0.0014). The presence of JET did not correlate with electrolyte abnormalities. JET is not necessarily related to surgery near the His bundle or hypomagnesemia. Longer ischemic time is the best predictor of JET. Patients undergoing arterial switch operation, AV canal repair, and Norwood repair are at highest risk of postoperative JET and should be considered for prophylactic therapy.

Modified Fontan operation in patients with anomalies of systemic and pulmonary venous connection.

The presence of anomalies of the systemic and pulmonary venous connection associated with single ventricle anomalies has been considered a contraindication for the Fontan operation (FO). The aim of this study is to outline the technical considerations associated with the presence of anomalies of systemic and/or pulmonary venous connections and to identify the risk factors for mortality in this group of patients undergoing the modified FO. Between 1989 and 2004, 63 patients (median age, 3.2 years) with anomalous systemic or pulmonary venous connection underwent a Fontan procedure at our institution. Nine patients had a combination of anomalous systemic and pulmonary venous connection, 49 patients had anomalous drainage only from the systemic circulation, and 5 patients had isolated anomalies of pulmonary venous return. Visceral heterotaxy syndrome was diagnosed in 25 patients. Previous palliative operations had been performed in 51 patients (81%). There was 1 early death, and 2 patients required take down of Fontan procedures. Two patients required reoperation for revision of the atrial baffle. At a mean follow-up of 4.6 +/- 3.4 years, there have been 5 late deaths (8%) and 45 patients (71%) have undergone Fontan completion. Actuarial survival was 92% at 1 year and 91% at 5 and 10 years-not significantly different from the overall survival of the Fontan patients. We conclude that the modified FO can be successfully performed in patients with anomalous systemic or pulmonary venous connections, including those with visceral heterotaxy syndrome, with morbidity and mortality rates that do not differ significantly from those achieved in all patients with normal connections.

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.

Pulmonary artery translocation: a surgical option for complex anomalous coronary artery anatomy.

Rather than perform a difficult and potentially high risk coronary reimplantation in a patient with an aberrant right coronary artery coursing between the aorta and pulmonary artery, the main pulmonary artery was translocated toward the left pulmonary hilum to create additional space between the aortic and pulmonic trunks.

[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.

Parahiatal hernia with volvulus and incarceration: laparoscopic repair of a rare defect.

A rare case of parahiatal hernia with gastric volvulus and incarceration is reported. An anatomically distinct diaphragmatic defect was present adjacent to a structurally normal esophageal hiatus. Laparoscopic repair was performed with excellent results.

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.

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.

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.

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.

Gap junction protein phenotypes of the human heart and conduction system.

INTRODUCTION: Gap junction channels are major determinants of intercellular resistance to current flow between cardiac myocytes. Alterations in gap junctions may contribute to development of arrhythmia substrates in patients. However, there is significant interspecies variation in the types and amounts of gap junction subunit proteins (connexins) expressed in disparate regions of mammalian hearts. To elucidate determinants of conduction properties in the human heart, we characterized connexin phenotypes of specific human cardiac tissues with different conduction properties. METHODS AND RESULTS: The distribution and relative abundance of Cx37, Cx40, Cx43, Cx45, and Cx46 were studied immunohistochemically using monospecific antibodies and frozen sections of the sinoatrial node and adjacent atria. AV node and His bundle, the bundle branches, and the left and right ventricular walls. Patterns of expression of these connexins in the human heart differed from those in previous animal studies. Sinus node gap junctions were small and sparse and contained Cx45 and apparently smaller amounts of Cx40 but no Cx43. AV node gap junctions were also small and contained mainly Cx45 and Cx40 but, unlike the sinus node, also expressed Cx43. Atrial gap junctions were larger than nodal junctions and contained moderate amounts of Cx40, Cx43, and Cx45. Junctions in the bundle branches were the largest in size and contained abundant amounts of Cx40, Cx43, and Cx45. Gap junctions in ventricular myocardium contained mainly Cx43 and Cx45; only a very small and amount of ventricular Cx40 was detected in subendocardial myocyte junctions and endothelial cells of small to medium sized intramural coronary arteries. Minimal Cx37 and Cx46 immunoreactivity was detected between occasional atrial or ventricular myocytes. CONCLUSIONS: The relative amounts of individual connexins and the number and size of gap junctions vary greatly in specific regions of the human heart with different conduction properties. These differences likely play a role in regulating cardiac conduction velocity. Differences in the connexin phenotypes of specific regions of the human heart and experimental animal hearts must be considered in future experimental or modeling studies of cardiac conduction.

Impaired hepatic bacterial clearance is reversed by surgical relief of obstructive jaundice.

Sepsis is a major cause of morbidity and mortality in infants with cholestatic jaundice. Previous studies have shown that biliary obstruction in rats causes a significant decrease in hepatic phagocytosis of viable Escherichia coli. This study tests this hypothesis and further evaluates whether the impaired function of the reticuloendothelial system of the liver (Kupffer cells) can be reversed by the relief of the biliary obstruction. Male Sprague-Dawley rats (weighing 140 to 150 g) were placed in three groups. Group I (n = 10) consisted of sham-operated controls. In Group II (n = 30), ligation and division of distal common bile duct (CDL) was performed. Group III (n = 30) underwent choledochoduodenostomy 2 weeks following ligation and division of common bile duct. At 1, 2, and 3 weeks following the operation, 10(9) 35S-radiolabeled viable E coli were injected intravenously via the tail vein. At 10 minutes, bacterial distribution in the liver, spleen, kidneys, and lungs was determined. Tissue samples (50 to 100 mg) from each organ were processed for liquid scintillation counting. The final distribution of bacteria was calculated from the input specific activity (dpm/bacteria) and expressed as the mean percentage of injected viable E coli per gram of tissue and per total organ weight. There was a significant decrease in the trapping of bacteria by the liver's Kupffer cells in rats in group II, at 2 and 3 weeks following CDL (45.0% +/- 14.0% and 15.1% +/- 4.9%, respectively, v controls 75.9% +/- 13.7%; P less than .005).(ABSTRACT TRUNCATED AT 250 WORDS)