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Biomedical subjects

S Bharati

Publications and source records attributed to S Bharati.

At least 37 records · Page 2Linked to original sources

The conduction system in sudden death in Alaskan sled dogs during the Iditarod race and/or during training.

Using serial section examination, we studied the conduction system in five Alaskan sled dogs that died suddenly; four during the Iditarod race and one during training. We compared our findings with the conduction system of three sled dogs of similar age that died of natural causes unrelated to the cardiovascular system. The conduction system of sudden death dogs revealed marked fibrosis of the sinoatrial (SA) node and/or its approaches and narrowing of the SA nodal artery in 3 dogs, fibrosis and marked fatty infiltration in and around the AV node in all 5, total isolation and/or tenuous connection of the AV node with its approaches in 4, fat and fibrosis in the AV bundle and bundle branches to a varying degree in all, and focal fibrotic scars in the left ventricle with fat and/or some disarray in 3. The control group revealed mild fibro-fatty changes in the conduction system without fibrotic scar areas in the heart. These findings are similar to the pathological findings in and around the conduction system in cases of sudden death in humans, especially trained athletes. These changes may form an anatomical substrate for an arrhythmic event in susceptible dogs during an altered physiological state.

Alaska↗

Pathologic findings following sudden death in an infant with hypertrophic cardiomyopathy and supraventricular tachycardia.

The cardiac conduction system from infants suddenly dying with hypertrophic cardiomyopathy has not been described. We studied by serial section examination the conduction system from a 13-month old infant also known to have had supraventricular tachycardia. At autopsy, there was cardiomegaly with asymmetric septal hypertrophy. Microscopic examination revealed myofiber disarray around an abnormally formed central fibrous body, numerous nodoventricular fibers to both sides of the ventricular septum, and fibrosis of the left bundle branch. We postulate that supraventricular tachycardia utilized a concealed pathway or the malformed AV junction. Death may have resulted from deranged hemodynamics secondary to supraventricular tachycardia.

Atrioventricular Node↗

Properties of a recombinant human uracil-DNA glycosylase from the UNG gene and evidence that UNG encodes the major uracil-DNA glycosylase.

We have expressed a human recombinant uracil-DNA glycosylase (UNG delta 84) closely resembling the mature form of the human enzyme (UNG, from the UNG gene) in Escherichia coli and purified the protein to apparent homogeneity. This form, which lacks the first seven nonconserved amino acids at the amino terminus, has properties similar to a 50% homogeneous UDG purified from human placenta except for a lower salt optimum and a slightly lower specific activity. The recombinant enzyme removed U from ssDNA approximately 3-fold more rapidly than from dsDNA. In the presence of 10 mM NaCl, Km values were 0.45 and 1.6 microM with ssDNA and dsDNA, respectively, but Km values increased significantly with higher NaCl concentrations. The pH optimum for UNG delta 84 was 7.7-8.0; the activation energy, 50.6 kJ/mol; and the pI between 10.4 and 10.8. The enzyme displays a striking sequence specificity in removal of U from UA base pairs in M13 dsDNA. The sequence specificity for removal of U from UG mismatches (simulating the situation after deamination of C) was essentially similar to removal from UA matches when examined in oligonucleotides. However, removal of U from UG mismatches was in general slightly faster, and in some cases significantly faster, than removal from UA base pairs. Immunofluorescence studies using polyclonal antibodies against UNG delta 84 demonstrated that the major fraction of UNG was located in the nucleus. Furthermore, > 98% of the total uracil-DNA glycosylase activity from HeLa cell extracts was inhibited by the antibodies, indicating that the UNG protein represents the major uracil-DNA glycosylase in the cells.

Base Sequence↗

Microwave ablation of the atrioventricular junction in open-chest dogs.

The use of microwave energy for ablation of the atrioventricular (AV) junction was examined in open-chest dogs. Using a specially designed microwave catheter and a 2450 MHz generator, microwave energy was delivered to the AV junction according to one of two protocols. In protocol 1, increasing amounts of energy were delivered until irreversible AV block occurred. In protocol 2, only two applications of energy were used, one at low energy and the other at an energy found to be high enough to cause irreversible AV block. Each dog received between one and six applications of microwave energy. The amount of energy delivered per application ranged from 25.6 to 311.4 J. No AV block was seen at 59.4 +/- 28.3 J. Reversible AV block was seen with an energy of 120.6 +/- 58 J. Irreversible AV block was seen at 188.1 +/- 75.9 J. Irreversible AV block could be achieved in each animal. There was no difference in the energy required to cause irreversible AV block between the two protocols. The tissue temperature measured near the tip of the microwave catheter was correlated with both the amount of energy delivered and the extent of AV block caused. Histologic examination demonstrated coagulation necrosis of the conduction system. Microwave energy is a feasible alternative energy source for myocardial ablation. Since tissue damage is due exclusively to heating and the resulting rise in temperature can be measured, microwave energy may have advantages over currently existing energy sources in terms of both titrating delivered energy and monitoring the extent of tissue destruction.

Animals↗

Cardiac conduction system involvement in sudden death of obese young people.

Involvement of the conduction system in the sudden death of obese young people has not been documented in the literature. We therefore studied the conduction system by serial section examination in 7 subjects, 5 obese and 2 mild to moderately obese, who died suddenly at ages 6, 11, 14, 16, 20, 30, and 32 years of age (5 males, 4 black and 1 white; two females, 1 black and 1 white). Three had a history of sleep apnea. The heart was hypertrophied and enlarged in 6; all 6 had a distinct ventricular septal bulge and epicardial coronary arteries were normal. All had focal mononuclear cells in and around the sinoatrial node and/or its approaches, with marked fat throughout the conduction system in 3, fibrosis of the atrioventricular (AV) bundle and/or the left bundle branch in 5, and the branching bundle sandwiched between the bulbar muscle and the summit of the ventricular septum in 5 (2 with left-sided bundle, 1 with loop formation, and 1 with a markedly fragmented bundle). The AV node was partly within the central fibrous body and/or the atrial septum in 6 patients; focal mononuclear cells were present to a varying degree, with focal fibrosis of the ventricular septum in 6 patients, arteriolosclerosis in 4, and myocardial disarray in 3. The mild to moderately obese patients demonstrated lesser amounts of fat with more fibrosis when compared with the markedly obese. In summary, there are significant pathologic findings in the conduction system in the sudden death of obese young people.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Hypoplasia of the eustachian valve and abnormal orientation of the limbus of the foramen ovale in hypoplastic left heart syndrome.

We examined the eustachian valve and the limbus of the foramen ovale in 42 hearts with hypoplastic left heart syndrome (HLHS) and in 16 normal hearts. In HLHS, only 4.8% of the eustachian valves were moderately to well developed, whereas the remaining 95.2% were abnormal (p < 0.001): 92.9% of the eustachian valves were absent or markedly hypoplastic, and 2.4% had an abnormally redundant and enlarged eustachian valve. The eustachian valve was well developed in 87.5% of normal hearts. In addition, the lesser development of the eustachian valve seemed to correlate with lesser development of the left side of the heart. The limbus was well developed in 100% of the normal hearts and moderately to well developed in only 33.3% of the HLHS group (p < 0.001). Most hearts in the HLHS group had marked hypoplasia of the limbus, which was rotated and deviated so as to be close to the superior vena caval entrance.

Aortic Valve↗

Intermittent preexcitation and mesothelioma of the atrioventricular node: a hitherto undescribed entity.

This is the first documented case of spontaneous intermittent preexcitation associated with mesothelioma of the atrioventricular (AV) node. A 66-year-old male with recurrent atrial arrhythmias, palpitations, heart failure, and marked intra-atrial conduction defect that required a pacemaker died during sleep. Electrophysiologic study revealed left free-wall bypass tract with marked intra-atrial conduction defect and prolonged conduction across the bypass tract. With atrial pacing, high degrees of block were noted in the bypass tract. Serial section of the conduction system and both AV rims revealed two left posterior and lateral bypass pathways with patchy areas of fibrosis. A large mesothelioma (benign AV nodal tumor) almost completely replaced the AV node. In addition, there was marked fatty infiltration of the atria. In summary: (1) the intermittent preexcitation with prolonged conduction across the bypass tract and block with atrial pacing were probably related to the incomplete patchy degenerative changes in the bypass tract, and/or almost complete replacement of the AV node by the tumor; (2) the intra-atrial conduction defect was probably related to the replacement of the AV node by mesothelioma and/or the fatty infiltration of the atria; and (3) the paroxysmal atrial arrhythmias probably reflect the marked atrial pathology.

Aged↗

Alternatives in biventricular repair of double-outlet left ventricle.

Wide variation in morphology of double-outlet left ventricle allows numerous surgical alternatives that require sorting out to develop a more organized approach. There is a high association between tricuspid abnormalities and right ventricular hypoplasia with double-outlet left ventricle that calls for either Fontan-type procedure or biventricular repair. With pulmonic stenosis, biventricular repair has been accomplished using right-sided conduits. When pulmonic stenosis is mild or absent, repair techniques without conduits depend on the commitment of the ventricular septal defect (VSD). With subaortic VSD and mild pulmonic valvar stenosis, we successfully performed translocation of the main pulmonary artery and valve to the right ventricle on 2 patients (ages 32 and 8 months). Both patients are doing well 2 years and 1 year postoperatively. Others have successfully connected the right ventricle to the pulmonary artery with intraventricular baffle by enlarging a subaortic VSD or when the VSD is either subpulmonic or doubly committed. With subaortic VSD, although it has not been reported, biventricular repair can also be accomplished using a right ventricle-to-aorta baffle combined by either atrial or arterial switch. We believe that a simplified management plan can be formed in double outlet left ventricle based on the size of the right ventricle, presence of pulmonic stenosis, and commitment of the VSD. Whenever possible, translocation of the main pulmonary artery and valve or intraventricular repair should be accomplished in double-outlet right ventricle minimizing the use of right-sided conduits and reoperation.

Cardiac Surgical Procedures↗

Conduction system findings in sudden death in young adults with a history of bronchial asthma.

OBJECTIVES: This study was conducted to determine whether there are any pathologic changes in the conduction system when death occurs suddenly in young adults with a history of bronchial asthma. BACKGROUND: There is a worldwide increase in sudden death, especially in young adults with a history of bronchial asthma. METHODS: We studied the conduction system by serial section examination in six male patients (16 to 23 years old) with a history of bronchial asthma who died suddenly. RESULTS: The sinoatrial node artery was narrowed in two patients, with chronic inflammatory cells in three; it was fibrosed in one. The atrioventricular (AV) node was within the central fibrous body in three patients and isolated by fat in one. The AV bundle was markedly fragmented in five patients and fibrosed in two. The right and left bundle branches showed fat, fibrosis and disruption in five patients. Increased fibrosis on the summit of the ventricular septum with patchy fibrosis was present in five patients, and inflammatory cells in the conduction system were found in one. CONCLUSIONS: 1) There are distinct pathologic findings in the conduction system of young adults with a history of bronchial asthma who die suddenly. 2) The significant findings appear to be a markedly fragmented bundle and changes in the sinoatrial node that are not found in normal healthy young adults. 3) The changes in the conduction system may create an arrhythmic event, and sudden death may occur in some persons during an altered physiologic state. 4) We hypothesize that bronchial asthma may be associated with an alteration in immune complexes that affects the conduction system in some patients.

Adolescent↗

Pulmonary valve eccentricity in d-transposition of the great arteries and implications for the arterial switch operation.

Neoaortic valve regurgitation is a known complication of the arterial switch operation for d-transposition. Its etiology and long-term effects are undetermined. Observations of pathologic specimens from 67 patients with d-transposition of the great arteries with or without ventricular septal defects demonstrated that the pulmonary valve leaflets had unequal cusp sizes leading to eccentric closure. The posterior cusp was usually the largest and was anatomically related to the membranous ventricular septum and the anterior leaflet of the mitral valve. The right cusp was usually the smallest. Differences in cusp sizes were unrelated to age at death, sex or presence of a ventricular septal defect. To determine if eccentricity could be clinically detected, the pulmonary valves in 24 sequential patients with d-transposition were studied echocardiographically and angiographically. Aortic valves were studied for comparison. All pulmonary valves demonstrated eccentric closure in the long-axis echo plane, posterior in 15 patients and anterior in 9. Only 1 aortic valve showed eccentricity. Angiographic findings correlated with echo findings. Sixteen patients underwent arterial switch operations; 3 died. Twelve had angiography at 1 year. Eleven had neoaortic valve regurgitation: 5 grade I, 4 grade II and 2 grade III.

Adolescent↗

Histopathological study following catheter guided radiofrequency current ablation of the slow pathway in a patient with atrioventricular nodal reentrant tachycardia.

The present study examined histological changes induced by catheter guided radiofrequency current in a patient with AV nodal reentrant tachycardia who underwent cardiac transplantation 1 week after ablation of the slow pathway. During the electrophysiology study AV nodal conduction curves were discontinuous and AV nodal reentry was induced. At the conclusion of the procedure there was no evidence of slow pathway function. Histological sections from the explanted heart demonstrated a sharply demarcated atrial lesion (5 x 5 x 4 mm) extending from the septal portion of the tricuspid annulus to the posterior border of the AV node. The lesion did not encompass the compact AV node. These observations support the hypothesis that the slow pathway is comprised of atrial approaches to the AV node and is distinct from the compact AV node.

Adipose Tissue↗

Histopathological changes following laser ablation of a left-sided accessory pathway in a human.

Laser ablation was performed intraoperatively in a patient with coronary artery disease and Wolff-Parkinson-White syndrome. Histopathological evaluation of the laser ablation site revealed a transverse laser incision in the left atrial septum and mitral valve annulus. There was hemorrhage in the atrioventricular (AV) groove with interruption of a posterolateral AV connection. The laser lesion was confined largely to the atrial aspect of the AV annulus. We conclude that laser catheter ablation of accessory pathways is feasible in humans.

Atrioventricular Node↗

The conduction system findings in sudden cardiac death.

This is a brief review of the findings in the conduction system in cases of sudden death victims who were living "normal" active lives. Twenty-two representative samples from more than 100 cases of sudden cardiac death, especially in young and asymptomatic individuals, revealed a plethora of findings that varied from normal to congenital and acquired changes, in most cases either at the gross or microscopic level, especially in the conduction system to a varying degree. Despite these changes, the individuals were living normal, symptom-free lives and were not clinically diagnosed to have lethal cardiac problems. This suggests that these individuals might have experienced lethal arrhythmias in the past, which might have been "silent" in nature. Innovative new methodologies must be developed to detect the silent lethal arrhythmic focus that may lead to sudden cardiac death.

Adolescent↗

Unifocalization of major aortopulmonary collateral arteries in pulmonary atresia and ventricular septal defect using antibiotic sterilized pulmonary homograft: a case report.

A unifocalization procedure in a 9-year-old girl with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries (MAPCAs) was performed using an antibiotic sterilized pulmonary homograft. A tailored pulmonary homograft was used as an interposition graft to anastomose the pulmonary artery to the larger MAPCA after a side-to-side anastomosis had been done between the two MAPCAs. The pulmonary homograft was connected to the right subclavin artery with a 6-mm Gore-Tex shunt. Postoperative oxygen saturation (SaO2) levels were satisfactory and a postoperative angiogram showed good unifocalization of the pulmonary vasculature.

Anastomosis, Surgical↗

Surgical correction of anomalous origin of the left coronary artery from the pulmonary artery.

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly seen in 0.26% of all congenital heart defects. From 1978 to the present, we have encountered 11 such cases in patients ranging from 3 months to 60 years of age. A variety of procedures have been performed, such as ligation of the anomalous left coronary artery (n = 1), saphenous vein bypass (n = 2), subclavian to left coronary artery anastomosis (n = 4), Takeuchi repair (n = 1), and revascularization using a 6-mm Gore-Tex tube (n = 1). Two of these patients were children who also had prosthetic mitral valve replacements with a #1 M Starr-Edwards valve and left subclavian to left coronary artery anastomosis. Three patients died postoperatively, one immediately after surgery due to low cardiac output, another on the eighth postoperative day due to renal failure, and the third was a child who died 3 months later due to bacterial endocarditis of the prosthetic valve. The surviving patients have been and are in NYHA Class I after a mean follow-up of 9 years. One patient, revascularized with a prosthetic graft, was lost for follow-up after 3 years. A two-coronary system appears more physiological and is reported to be favored by most surgeons. Left subclavian to left coronary artery anastomosis has also been observed to give excellent results, with which we also agree. The mitral valve replacement in addition to this procedure, reported here, has not been described before in the literature.

Adolescent↗

Selective elimination of retrograde conduction by intraoperative neodymium: YAG laser photocoagulation in dogs.

OBJECTIVES: The purpose of this study was to test the feasibility of selective elimination of ventriculoatrial (VA) conduction by limited laser photocoagulation of the atrioventricular (AV) node, and to analyze the histologic substrate of unidirectional retrograde block. BACKGROUND: Atrioventricular node reentry requires intact retrograde conduction. METHODS: Neodymium:yttrium-aluminum-garnet laser photocoagulation was performed during cardiopulmonary bypass through a right atriotomy in 15 dogs that had intact retrograde conduction before operation. Short laser pulses were delivered to an area between the coronary sinus orifice and the proximal His bundle. The end point of lasing was second-degree AV node block at a paced atrial cycle length of 250 ms. RESULTS: Complete retrograde block developed immediately in 11 of the 15 dogs (group I), while AV conduction persisted in all 11. In 4 of the 15 dogs (group II), both AV and VA conduction remained intact. During a 3-month follow-up period, retrograde conduction remained absent in all group I dogs. Retrograde block was not reversed by isoproterenol. Anterograde AV node characteristics (Wenckebach cycle length, functional refractory period, ventricular rate during atrial fibrillation) were unchanged in five dogs and modified in six. Complete AV block did not develop. In four control dogs (group III, sham operation), anterograde and retrograde AV node characteristics were unchanged. The anterograde Wenckebach cycle lengths in groups I, II and III at 3 months measured 192 +/- 15 ms, 195 +/- 6 ms and 170 +/- 22 ms, respectively, whereas the retrograde Wenckebach cycle lengths in groups II and III measured 345 +/- 62 ms and 278 +/- 25 ms, respectively. Histologic study at 3 months in cases with unidirectional VA block showed the compact part of the AV node intact with destruction of the atrial approaches and the superficial layers of the proximal end of the node on the right side. CONCLUSIONS: 1) With limited laser photocoagulation of the proximal AV node area, VA conduction can be eliminated and anterograde AV node transmission maintained. 2) Destruction of the atrial approaches on the right side with preservation of the compact part of the AV node may result in unidirectional retrograde block.

Animals↗