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Biomedical subjects

M Lev

Publications and source records attributed to M Lev.

At least 55 records · Page 3Linked to original sources

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↗

Transcatheter radiofrequency ablation in the canine right atrium.

The feasibility of using radiofrequency energy for potential ablation of atrial tachycardia foci was assessed by performing transcatheter ablation in the right atrium in 11 closed-chest dogs. Single-pulsed radiofrequency (750 kHz) energy was delivered to the right atrium (29-254 J) between the tip electrode of a standard 6 Fr quadripolar catheter and a chest patch electrode. There were no significant arrhythmias or complications noted. Dogs were sacrificed 0-29 days after ablation to assess acute and subacute effects of this technique. Of 47 attempted ablations, 36 well-delineated coagulative lesions were identified. The lesions had a mean dimension of 5.2 +/- 0.57 mm (+/- SE) in length, 3.9 +/- 0.27 mm in width, and 2.6 +/- 0.17 mm in depth. Transmural necrosis was noted in 6 of 36 lesions (17%) without perforation. A thin layer of mural thrombus was found in 5 of 36 lesions (14%). Thus, this technique appears to be feasible and relatively safe for right atrial ablations in a short-term follow-up period. The potential application of this method to ablate right atrial tachycardia foci needs to be further investigated.

Animals↗

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↗

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↗

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↗

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↗

Modification of sinus node function by epicardial laser irradiation in dogs.

This study tested the feasibility of neodymium:YAG laser photocoagulation of selected sinus node areas to depress sinus rate responsiveness. In 14 open-chest dogs, origin of the sinus impulse (O point) was electrically mapped from the epicardium before and during isoproterenol infusion. Epicardial laser photocoagulation was applied to the O point observed during isoproterenol infusion and stepwise to remapped new O points until a 30 +/- 5% decrease in heart rate occurred. Long-term effects were assessed by Holter monitoring and electropharmacologic testing preoperatively and up to 10 weeks or 6 months. Mean (+/- SEM) percent decreases were observed at 10 weeks in the following parameters: average 24-hour heart rate, 17.4 +/- 5.0%; maximum heart rate on Holter, 30.5 +/- 3.5%; heart rate during pharmacologic autonomic blockade, 32.7 +/- 3.5%; and maximum heart rate on isoproterenol, 23.1 +/- 4.6% (all p less than 0.01). Curves with pacemaker recovery time plotted against control cycle length remained unchanged. Holter monitoring did not show excessive bradycardic episodes even after administration of propranolol. In three control dogs (sham operation), sinus node function remained unchanged. Histologic study of the irradiated area showed replacement by inflammatory cells, fibrosis, and cartilage formation with surrounding normal cells and occasional cells resembling pacemaker-like cells at the caudal end of the sinoatrial node. This study suggests that 1) map-guided graded laser photocoagulation of sinus node regions showing earliest activation during catecholamine stimulation successfully limits maximum heart rates without causing significant bradycardia, 2) the effects are long lasting, and 3) the remaining pacemaker behaves like the sinus node. Laser modification of sinus node function could become a form of nonpharmacologic heart rate control in patients with coronary artery disease undergoing surgery and in the syndrome of inappropriate sinus tachycardia.

Animals↗

Morphological and electrophysiological correlates of atrioventricular nodal response to increased vagal activity.

The mechanisms responsible for slowing cardiac impulse conduction through the atrioventricular (AV) node are not well understood but include anatomical architecture, presence of cells with diverse electrophysiological characteristics, and modulation by autonomic nervous system. The present study was designed to determine the site of vagally induced slowing of conduction through the AV node. We attempted to correlate the electrophysiological response of AV nodal cells to postganglionic vagal stimulation applied in different regions of the node with the morphological findings and patterns of acetylcholinesterase-positive staining of nodal tissue. This multifaceted approach revealed that vagal stimulation produced localized hyperpolarization of the cells from the N region of the AV node, which correlated with the strong acetylcholinesterase positive staining of the central nodal area. In contrast, the density of the acetylcholinesterase staining decreased toward both the AN and His bundle regions, whereas vagal stimulation had a negligible effect on the cells from these regions. These results suggest that vagal-induced depression of AV nodal conduction is produced by release of acetylcholine predominantly around the midnodal region and the depressive action of acetylcholine is concentrated on the cells occupying the same region (i.e., the N cells). Thus, there appears to be a close juxtaposition of nerve elements and effector cells in the midnodal region of the AV node. This unique combination of available neuromediator and responding cells with hyperpolarization and depressed action potential determines the midnodal region as the focus of vagal effect on AV nodal conduction.

Animals↗

The long-term administration of L-cycloserine to mice: specific reduction of cerebroside level.

Short-term experiments in which L-cycloserine, the inhibitor of 3-ketodihydrosphinogosine synthase, was injected subcutaneously in young mice have shown that cerebroside synthesis is inhibited specifically. Studies on the effect of long term L-cycloserine treatment on sphingolipid synthesis were performed to determine whether mice could tolerate continued cerebroside reduction and whether or not the synthesis of other sphingolipids would be inhibited. L-cycloserine, when injected at a low dose for a period of two months resulted in significantly reduced brain cerebroside level with little or no reduction in sulfatide, ganglioside, or sphingomyelin levels; liver and spleen glucocerebroside levels were also significantly reduced. The rate of cerebroside synthesis in brain was greatly reduced, whereas synthesis of sulfatides was much less affected by L-cycloserine indicating that a portion of newly synthesized galactocerebroside is shunted to synthesis of sulfatides.

Animals↗

Small aortic valve annulus in children with fixed subaortic stenosis.

Twenty-one hearts with fixed subaortic stenosis (FSAS) were examined pathologically. Thirty children with no hemodynamically significant heart disease, 31 children with valvar aortic stenosis, and 25 children with FSAS were studied by echo- and angiocardiography. The following conclusions were drawn: (1) Patients with FSAS often have abnormal aortic valve leaflets as well as small aortic valve annulus. (2) A small aortic annulus/descending aorta ratio is probably present at birth, and may decrease with increasing age. (3) In some patients with FSAS the aortic valve annulus is too small for simple resection of the fibroelastic tissue. A Konno operation is needed for these patients. (4) M-mode echocardiography has not been useful in identifying abnormally small aortic valve annulus in FSAS patients.

Adolescent↗

Catheter ablation of the ventricular septum with radiofrequency energy.

The safety and feasibility of performing catheter ablation of the ventricular septum with radiofrequency energy was assessed in a closed-chest canine model. Radiofrequency energy (750 kHz) was delivered in a bipolar manner via the distal electrodes of two quadripolar catheters positioned across the ventricular septum in 10 dogs at two sites. Each site received from 159 to 823 joules of delivered energy over one to three applications. Four additional dogs underwent unipolar radiofrequency ablation with 331 to 767 joules of delivered energy to each septal site. No significant acute or latent arrhythmias were noted. Dogs were killed at 1 day, and at 1, 2, and 4 weeks after the procedure. Out of a possible 40 potential ablation sites on each side of the septum after bipolar ablation, 21 (53%) discrete endocardial lesions were identified, ranging in size from 4 x 3 x 1.5 to 10 x 8 x 4 mm. When 352 joules or more delivered energy was applied per site, lesions were located at 18 of 28 (64%) possible sites. After unipolar radiofrequency ablation, similarly sized lesions were identified at 15 of 16 (94%) ablation sites. Histologic examination demonstrated well-delineated round or ovoid-shaped lesions with microscopic thrombi overlying two lesions. In conclusion, catheter ablation of the ventricular septum with radiofrequency energy appears capable of safely producing discrete areas of necrosis and may provide an alternative to direct current (DC) energy for catheter ablation of ventricular tachycardia originating from the septum.

Animals↗

Catheter ablation of accessory pathways using radiofrequency energy in the canine coronary sinus.

Ablation of a left-sided accessory pathway with high energy direct-current shocks delivered by an electrode catheter in the coronary sinus is associated with the risk of coronary sinus rupture. The safety and effectiveness of closed chest catheter desiccation in the coronary sinus with use of radiofrequency energy was studied. Radiofrequency energy (174 +/- 74 J) was applied between the distal electrode of a standard electrode catheter placed 3 to 6 cm inside the coronary sinus and a large posterior chest wall patch in 16 dogs. No arrhythmias or hemodynamic changes were observed. Three dogs were killed approximately 1 h after ablation and 13 after 2 to 4 weeks. Lesions in the atrioventricular (AV) sulcus were observed in 14 of 16 dogs. Lesions were 11.6 +/- 6 mm in length, 4.3 +/- 2.3 mm in width and 2.8 +/- 1.4 mm in depth. Microscopic examination showed well circumscribed areas of necrosis and fibrosis in the fat of the AV sulcus. The media and intima of the circumflex coronary artery were not involved nor was the endocardium or mitral apparatus damaged in any dog. Coronary sinus thrombus was present in 3 of 16 dogs. Large amounts of radiofrequency energy can be safely applied to the coronary sinus. The size and location of the lesions produced suggest that this technique may be useful for the interruption of left-sided accessory AV connections in humans.

Animals↗

Histopathologic changes in the heart including the conduction system after catheter ablation.

The pathology of the heart, including that of the conduction system, after various catheter techniques used to ablate the various parts of the conduction system and the myocardium, were examined histologically by serial sections. The experiments were conducted on canines. The conduction system studies included the approaches to the AV node, the AV node, the AV bundle and bundle branches, as well as, the central fibrous body, the tricuspid, mitral and aortic valves. The methods of ablation were DC shock, laser and radio frequency energy. Production of the complete AV block clinically was associated with fibrosis with or without cartilage formation of the approaches to the AV node, the AV node, the bundle and the beginning of the bundle branches in most cases. On the other hand, creation of first degree AV block was associated with fibrotic changes in the approaches to the AV node and the AV node, and second degree block with more changes to the AV node. Coronary sinus ablation resulted in necrosis and fibrosis of the coronary sinus wall with occasional thrombosis of the coronary sinus. The adjacent atrial and/or the ventricular myocardium also showed fibrosis. Likewise, ventricular septal ablation was associated with focal areas of fibrosis of the myocardium. The conduction system was intact in both of the above experiments. In one human where complete AV block was created to manage intractable atrial fibrillation, the AV node, the bundle, and the bundle branches were fibrosed. In addition, there was a fibrosed atrio-Hisian connection and the patient died suddenly six weeks after the ablative procedure. The surrounding structures close to the vicinity of the conduction system, such as the aortic, tricuspid, mitral valve, the central fibrous body, and the summit ventricular septum are involved to a varying degree. In summary, (1) Whatever the method of ablation may be, the end result was fibrosis with or without cartilage formation of the ablative area. (2) Congenital anomalies of the conduction system such as an atrio-Hisian connection may remain elusive for ablative methods, and arrhythmias may persist and may cause sudden death in some cases.

Animals↗

Chronic incomplete atrioventricular block induced by radiofrequency catheter ablation.

To determine if catheter ablation of the atrioventricular (AV) junction with radiofrequency energy can induce chronic incomplete (first- and second-degree) AV block to avoid the need for a permanent pacemaker, 20 closed-chest dogs were studied. Group 1 (10 dogs) received radiofrequency energy (750 kHz) with a fixed power setting (5 or 10 W) while increasing the pulse duration from 10 to 50 seconds for each application. Group 2 (10 dogs) received energy with a fixed pulse duration (20 or 30 seconds) while increasing the power setting from 5 to 10 W or from 10 to 20 W during each energy delivery. Radiofrequency energy was delivered between a chest-patch electrode and the distal electrode of a regular 7F tripolar His bundle catheter. For each application, the energy delivery was interrupted when 1) the PR interval prolonged (greater than 50%) or 2) second-degree or complete AV block occurred and persisted up to 5 seconds. The ablation procedure ended when there was 1) persistent PR prolongation (greater than 50%) or persistent second-degree AV block (lasting greater than 30 minutes) after ablation, 2) occurrence of two consecutive transient (less than 1 minute) complete AV blocks after each energy delivery, or 3) complete AV block (lasting greater than 2 minutes) after ablation. Of seven dogs in group 1 and five dogs in group 2 in which incomplete AV block was achieved 1 hour after the procedure, six in group 1 and five in group 2 remained in incomplete AV block 2-3 months after ablation. One dog in group 1 progressed into complete AV block. Of the remaining three dogs in group 1 and five dogs in group 2 in which complete AV block was initially achieved 1 hour after ablation, two in group 1 and four in group 2 continued to have complete AV block, whereas one in each group had AV conduction returned to incomplete at 1-2 months of follow-up. Thus, a total of 13 dogs had chronic incomplete AV block induced by radiofrequency catheter ablation. Pathologic examination of the conduction system in two dogs with first-degree AV block, two dogs with second-degree AV block, and one dog with complete AV block showed discrete scars involving the approaches to the AV node and the AV node itself. It is concluded that, in most dogs studied, chronic incomplete AV block could be achieved by careful titration of the dosage of radiofrequency energy and by regulation of the ablation end points.

Animals↗

Conduction system in children with acquired immunodeficiency syndrome.

Six children died of acquired immunodeficiency syndrome (AIDS), four of them females, ages 7 months, 13 months, 2 years 8 months, and 4 years; and two of them males, aged 2 1/2 and 7 years. They were born to IV drug-addicted parents. The conduction system (CS) and the entire heart were studied by serial section. In all cases the heart was hypertrophied and enlarged; one had total thrombotic occlusion of the right coronary artery with extensive infarction of the ventricular septum. Vascular changes also were found in all hearts, involving small arteries, arterioles, and venules. In the arteries, they involved the intima, media, and adventitia, and perivascular areas in a degenerative and inflammatory process. The elastic tissue was especially affected. A nonspecific myocarditis was present in four cases and epicarditis in all. Changes in the summit of the ventricular septum were present in four cases, consisting of increased fibrosis and arteriolosclerosis. The CS changes varied in location, showing either vasculitis, myocarditis, or fragmentation of the bundle with lobulation and fibrosis. The changes in the conduction system were not as severe as the changes in the surrounding myocardium. In one case the ECG was abnormal, showing left hemiblock. This corresponded to the finding of fibrosis, vacuolization of cells, and space formation in the left bundle branch.

Acquired Immunodeficiency Syndrome↗