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Biomedical subjects

M Lev

Publications and source records attributed to M Lev.

At least 19 recordsLinked to original sources
PubMed1992

Purification and activation of brain sulfotransferase.

Galactosylceramide sulfotransferase (EC 2.8.2.11) catalyzes the biosynthesis of sulfatide from galactocerebroside and adenosine 3'-phosphate 5'-phosphosulfate (PAPS). This enzyme is developmentally controlled, reaching a maximum activity in the brains of mice corresponding to that of maximum myelination. The product, sulfatide, is an important component of myelin. This transferase from mouse brain has been purified 2600-fold using a combination of pyridoxal 5'-phosphate- and ATP-ligated columns. The purified enzyme yielded a single band following SDS-polyacrylamide gel electrophoresis with an apparent M(r) of 31,000. The entire purification procedure can be completed in 1 day. The pH optimum for the enzyme is 7.0. The Km for PAPS is 1.2 x 10(-6) M, and the Km for cerebroside is 2.6 x 10(-5) M. Cerebroside concentrations > 80 pmol/ml are inhibitory. Enzyme preparations were associated with several lipids. Vitamin K+P(i) activated purified preparations of the sulfotransferase and maintained enzyme activity during storage at -80 degrees C.

Adenosine Triphosphate↗
PubMed1992

The pathologic changes in the conduction system beyond the age of ninety.

The conduction systems of two women who were 92 and 91 years of age, respectively, were examined by serial section. The first patient had sick sinus syndrome for more than 20 years, and the second patient had intermittent complete AV block that alternated with normal sinus rhythm for 12 years before her death. Both patients had severe coronary artery disease and had pacemakers and were doing well. The conduction systems in both revealed fatty metamorphosis in the approaches to the SA and AV nodes, the SA node, the AV node, and the atria with fibrotic changes in the ventricular septum, the AV bundle, and the bundle branches. Patient 1 had normal SA nodal artery and patient 2 had extensive vascularization of the AV node. As the heart ages, fatty replacement of the atria affect the SA and AV nodes, and fibrotic changes of the ventricular septum affect the AV bundle and the bundle branches. Adequate collateral anastomosis to the conduction system may prevent the development of permanent complete AV block in the elderly.

Aged↗
PubMed1992

Dissociation of atrioventricular conduction and refractoriness following application of radiofrequency energy to the canine atrioventricular node: acute and chronic observations.

The electrophysiology of AV nodal modification induced by radiofrequency energy (n = 5) or a sham procedure (n = 5) was studied in ten dogs. The five dogs that received radiofrequency energy had an AH prolongation > 100% from baseline values and this prolongation persisted throughout the 2-month study. The AV nodal functional refractory period was prolonged only acutely. These data indicate a dissociation between the effects on AV nodal conduction and refractoriness that was induced by this procedure. The five sham treated controls showed no acute or chronic electrophysiological changes. In the dogs that received radiofrequency energy, there was fibrosis of the approaches to the AV node and the region of the AV node itself. It is concluded that chronic modification of AV nodal conduction without concomitant changes in refractoriness can be induced by radiofrequency energy delivered in the proximal portion of the AV node. It would be anticipated that this procedure would not decrease the ventricular response to atrial fibrillation or flutter, may be effective in preventing AV nodal reentrant tachycardia by interfering with conduction either in the AV node or perinodal region. Since the AV node itself suffers at least moderate pathological damage, there may be an appreciable incidence of the late development of complete heart block after this procedure.

Animals↗
PubMed1992

Familial congenital sinus rhythm anomalies: clinical and pathological correlations.

We describe pathological abnormalities in a 72-year-old male member of a family with a congenital absence of sinus rhythm and a tendency to develop atrial fibrillation at an early age, and in a 54-year-old female member of a family with cardiomyopathy and progressive conduction system disease manifested by first-degree atrioventricular (AV) block, left bundle branch block, and atrial arrhythmias. Both patients died suddenly. The absence of sinus rhythm in case 1 could be explained by marked atrophy, degeneration, and isolation of the sinoatrial (SA) node. The SA node was also diseased in the member of the other family with atrial arrhythmias. Additional common features in both cases included: fatty metamorphosis and degenerative changes of the approaches to the SA node, the atrial preferential fibers, and the approaches to the AV node, a small AV node, degenerative changes of the bundle branches, and floppy AV valves. These findings show that the pathological substrate of familial supraventricular arrhythmias consists of a diffuse involvement of the entire conduction system, bearing resemblance to pathological findings in elderly subjects with acquired sick sinus syndrome.

Aged↗
PubMed1992

Histologic findings of the heart and the conduction system in the first patient who underwent catheter ablation.

This is a detailed pathological examination of the heart including the conduction system (CS) from a 64-year-old male who had catheter ablation of the atrioventricular (AV) junction for intractable atrial fibrillation. This is the world's first human who had this procedure, and who survived 3 years and 8 months, and later died of congestive heart failure. Pathologically, the heart was hypertrophied and enlarged. Histologically, there were chronic inflammatory cells, marked fatty metamorphosis with fibrosis of the atria, the approaches to the AV node, and the AV node, with almost isolation of the node from the atria, and considerable fibrosis of the bundle and bundle branches. In addition, there was fibrosis of the summit of the ventricular septum with chronic inflammatory cells. These represent the sequelae of the ablation procedures. It is not known how much of the pathological findings contributed to the cardiac hypertrophy and impairment of cardiac function.

Atrial Fibrillation↗
PubMed1992

Effects of physiological aging on cardiac electrophysiology in perfused Fischer 344 rat hearts.

Aging effects on heart rate and atrioventricular (AV) conduction were studied in Langendorff-perfused hearts from 18 mature (4-6 mo), 12 middle-aged (12-14 mo), and 18 senescent (24-26 mo) Fischer 344 rats. Heart rate decreased with increasing age from 218 +/- 18 in mature to 196 +/- 27 (mean +/- SD) beats/min in middle-aged rats to 183 +/- 22 beats/min in senescent rats (analysis of variance, P less than 0.001). Spontaneous AV conduction time increased from 43 +/- 7 to 49 +/- 5 to 62 +/- 9 ms with aging (P less than 0.0001). Paced AV conduction time also lengthened with aging, and AV Wenckebach block cycle length increased from 122 +/- 10 to 133 +/- 9 to 152 +/- 16 ms (P less than 0.005). Intra-atrial conduction time was unaffected by age. Age differences in heart rate and AV conduction responses to isoproterenol (0.5 x 10(-9) to 1 x 10(-7) M) were noted with greater sensitivity at lower doses in hearts from younger rats. In separate experiments, 18 mature and 19 senescent Fischer 344 rats received reserpine (0.25 mg.kg-1.day-1 ip) for 6 days before study. Age differences in heart rate and AV conduction persisted (P less than 0.0001). Histopathological examination of AV nodal and His-bundle tissues in three hearts from each age group showed increased intercellular collagen with advancing age.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1992

The conduction system in transplanted hearts.

This is a serial section examination of the conduction system (CS) in six patients who died seven months, 11 months, two years four months, four years two months, 11 years, and 16 years eight months following cardiac transplantation. The heart was hypertrophied and enlarged in all. There was myocarditis of varying degree in all cases with arteriosclerosis and arteriolosclerosis. These findings were more dominant in the atria than in the ventricles. In the CS, myocarditis with fibrosis was found in all in the approaches to the sinoatrial (SA) node, the SA node, the atria, the atrioventricular (AV) node, and the bundle and bundle branches, to a varying degree. When compared with the endomyocardial biopsy findings, the autopsied cases revealed more myocarditis and fibrosis than those estimated to be present in the biopsy specimen. In summary, this study demonstrates that there are fibrotic changes in the CS with the persistence of inflammatory phenomena of the myocardium and the CS to a varying degree in transplanted hearts. This is accompanied by the ubiquitous coronary artery disease affecting not only the large coronaries but also the small vessels. The pathologic changes in and around the CS may be responsible for arrhythmias and sudden death in some cases of cardiac transplantation.

Adolescent↗
PubMed1992

The conduction system in truncus arteriosus and its surgical significance. A study of five cases.

Atrioventricular block may occasionally occur after surgical correction of truncus arteriosus. We therefore studied the conduction system by means of serial sections in five cases of truncus (one after surgical intervention) to delineate the course of the conduction system and its relationship to the ventricular septal defect and the membranous septum. In general, the ventricular septal defect is in the anterior septum, confluent with the truncus, and the atrioventricular bundle is posterior and unrelated to the rim of the ventricular septal defect. In cases in which the ventricular septal defect is anterior and separated from the membranous septum by distinct muscle, the ventricular septal defect can be surgically closed without injury to the atrioventricular bundle. If the ventricular septal defect is related to the membranous septum, the atrioventricular bundle may be close to the ventricular septal defect and susceptible to surgical injury. If muscle separates the ventricular septal defect from the membranous septum, the branching bundle is close to the ventricular septal defect and also is susceptible to surgical injury. In one operated case there was partial dissolution of the left bundle branch, and the right bundle branch was involved in surgical closure of the defect. In summary, in truncus the conduction system varies in its course and is related to the location of the ventricular septal defect and its relationship to the membranous septum. The ventricular septal defect may be close to or related to the membranous septum, and the atrioventricular bundle and the beginning of the bundle branches may be vulnerable to surgical injury.

Atrioventricular Node↗
PubMed1991

Modification of atrioventricular node transmission properties by intraoperative neodymium-YAG laser photocoagulation in dogs.

The purpose of this study was to test the feasibility of neodymium-yttrium-aluminum-garnet (Nd-YAG) laser photocoagulation of the atrioventricular (AV) node to control the ventricular rate during rapid atrial rhythms without creating AV block. In 12 dogs on normothermic cardiopulmonary bypass, short laser pulses were delivered to an area between the coronary sinus orifice and the site of the most proximally recorded His deflection until second degree AV block occurred at a paced atrial rate of 200 beats/min. Long-term effects on AV node function were followed up for 3 months. Three animals developed chronic high grade AV block. In nine animals with preserved 1:1 conduction, the mean (+/- SEM) critical atrial cycle length resulting in AV node Wenckebach periodicity increased from 183 +/- 6 to 261 +/- 24 ms (+43%), the mean RR interval during induced atrial fibrillation increased from 248 +/- 14 to 330 +/- 27 ms (+32%) and the shortest RR interval during atrial fibrillation increased from 215 +/- 11 to 275 +/- 20 ms (+28%). Laser effects were not reversed by isoproterenol infusion. Histologic examination of the irradiated area showed fibrotic changes in the AV node and fatty metamorphosis. This study suggests that 1) graded Nd-YAG laser photocoagulation of the AV node region in dogs results in long-term modification of anterograde AV node transmission properties; 2) 1:1 conduction during sinus rhythm usually remains preserved, but ventricular rate during rapid atrial rhythms is chronically reduced; and 3) progression to high grade AV block occurs in a minority of animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Unique variant of Taussig-Bing heart: double-outlet right ventricle with double ventricular septal defects and double overriding of great arteries.

A cyanotic, tachypneic newborn was diagnosed to have double-outlet right ventricle of the Taussig-Bing type. Cardiac failure did not respond to medical treatment or surgical palliation. Postmortem examination revealed two ventricular septal defects (VSDs), one a malalignment VSD in the membranous septum and adjacent tissue and the other in the anterosuperior part of the muscular septum. The D-malposed aortic root emerged mainly from the right ventricle, with aortic-mitral continuity. The larger posterolateral pulmonary root arose almost entirely from the right ventricle, confluent with the muscular VSD, and unrelated to the mitral valve. Its right ventricular aspect was obstructed by hypertrophied infundibulum. This unique malformation of the heart functioned as a double-outlet right ventricle of Taussig-Bing type. In addition, however, the malformation had elements of tetralogy of Fallot because of the malaligned VSD and hypertrophied conal musculature (although pulmonary flow was excessive), and also of complete transposition of the great arteries because of the arrangements of the two VSDs, which favored aortic flow from right ventricle and pulmonary blood flow from the left ventricle. Thus, a single heart presented similarities to three anatomic and functional entities.

Double Outlet Right Ventricle↗
PubMed1991

Surgical options in subaortic stenosis associated with endocardial cushion defects.

Over a 15-year period, 12 patients with endocardial cushion defects undergoing correction had subaortic stenosis requiring operative intervention. Ages ranged from 4 months to 17 years (mean, 7 +/- 6 years) and subaortic gradients from 15 to 100 mm Hg (mean, 60 +/- 25 mm Hg). Subaortic stenosis was due to discrete fibromuscular tissues in 7 patients, mitral valve malattachment in 3, and tunnel outflow in 2. In 2, the subaortic stenosis was clinically significant at the time of endocardial cushion defects repair, whereas in 10 it was noted 2 to 14 years postoperatively (mean, 6.3 +/- 5 years). Surgical relief of subaortic stenosis was accomplished by resection of muscle tissues in 7, apicoaortic conduit insertion in 2, modified Konno procedure (aortic valve preserved) in 2, and lifting of malattached mitral valve from the outflow in 1. There was no early death and one late death (infected conduit). Severe mitral insufficiency developed in the patient who had the mitral valve lifted and necessitated valve replacement. Postoperative echocardiographic gradient in 9 patients ranged from 0 to 36 mm Hg (mean, 10.5 +/- 14 mm Hg). Clinically significant subaortic stenosis has not developed in any patient in 15 years of follow-up (mean, 5 +/- 4 years). We conclude that in subaortic stenosis associated with endocardial cushion defects, resection is effective for discrete obstruction, whereas a modified Konno procedure is preferable for obstruction due to tunnel outflow or mitral valve malattachment.

Aortic Valve Stenosis↗
PubMed1991

Junctional tachycardias: anatomic substrate and its significance in ablative procedures.

The conduction system was studied by serial section in three patients with intractable supraventricular tachycardias originating from the atrioventricular (AV) junction who died suddenly. The three patients were a 6 month old girl (Case 1), a 5 month old boy (Case 2) and a 22 year old woman (Case 3). The latter had a pacemaker inserted after surgical ablation of the AV node. The heart was hypertrophied and enlarged in all. In Case 1, the AV node was partly within the central fibrous body and there was a left-sided AV bundle with acute necrosis in the summit of the ventricular septum, adjacent to the AV node and bundle. In Case 2, the coronary sinus was displaced cranially close to the central fibrous body, resulting in abnormality of the latter, with entrapment, distortion and division of the AV node and bundle into two distinct components within the central fibrous body. In Case 3, a left-sided AV node was connected to the atrial septum. The right AV node was completely interrupted by sutures and the penetrating and branching bundle and bundle branches were markedly fibrosed. In addition, the atrial septum and summit of the ventricular septum showed marked inflammatory reaction with fibrosis, which was more marked on the right ventricular side. Histologic examination of the conduction system in all three cases demonstrated congenital abnormalities of the AV junction that may be related to the tachycardia. These findings emphasize the need to carefully evaluate the atrial septum and AV junctional area, including the coronary sinus, before ablative procedures are undertaken.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

The conduction system of the swine heart.

Although the pig has been used as an experimental model for ischemic heart disease and sudden death, relatively little is known about the anatomy of the conduction system (CS) of this animal. We attempted to correlate electrophysiologic and anatomic differences between the pig and human CS. Invasive electrophysiologic studies were performed in five healthy anesthetized pigs. In contrast to the adult human, the pig has sinus tachycardia, shortened PR and H-V intervals, and a relatively short sinoatrial conduction time. Compared with the human CS, serial sections of the CS of pig hearts showed the following differences: (1) the atrioventricular node is located more to the right of the summit of the ventricular septum; (2) the penetrating bundle is very short, and the bifurcation of the bundle into bundle branches occurs more proximally; (3) there is more connective tissue and less elastic tissue; and (4) there is a copious amount of nerve fibers (about 50 percent throughout the CS). The presence of the abundant neural tissue implies that there is an important neurogenic component to conduction in the pig. Because of the above differences from the human, the pig should be used with caution as an experimental model in ischemic heart disease and sudden death where arrhythmias are studied.

Animals↗
PubMed1990

Vitamin K and phosphate mediated enhancement of brain sulfotransferase activity.

Previous work has shown that vitamin K regulates brain sulfotransferase activity. We now show that activity is lost after treatment with acid phosphatase and is restored with ATP. Orthophosphate activates sulfotransferase to a small degree (26%) with a maximum at 3 mM. Vitamin K1 (or menadione) + orthophosphate stimulates activity 400%; vitamin K alone is not active. ATP activates maximally at 10 mM; ATP + vitamin K increases activation 20%. Protein kinase inhibitors do not affect ATP or orthophosphate + vitamin K mediated activation. Sulfotransferase is inhibited by pyridoxal phosphate indicating modification of a lysyl residue.

Acid Phosphatase↗
PubMed1990

Regulation of sulfotransferase activity by vitamin K in mouse brain.

We have shown previously that the administration of warfarin to 16-day-old mice results in a significant reduction in levels of sulfatides, and to a lesser degree a reduction of other sphingolipids in brain. Vitamin K stimulates biosynthesis of sulfatides in warfarin-treated mice. We now report that warfarin inhibits brain sulfotransferase activity. This inhibition is reversed by vitamin K. The treatment of normal mice with vitamin K stimulates the activities of sulfotransferase and arylsulfatase and the turnover rate of brain sulfatides. The ability of vitamin K to influence the activity of biosynthetic and catabolic enzymes and the turnover of sulfatides suggests a possible regulatory role for vitamin K in the maturing brain.

Animals↗
PubMed1990

The heart and conduction system in acute Kawasaki disease: report of fraternal cases--one lethal, one relapsing.

The heart and conduction system were studied in a 4 1/2-year-old boy with Kawasaki disease who died suddenly in the early phase of illness. Severe perivasculitis, neuritis, pancarditis, and involvement of all parts of the specialized conduction system were found. The boy's brother, born a year later, at the age of 12 months had relapsing Kawasaki disease. He received intravenous gamma globulin and recovered.

Aorta↗