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Biomedical subjects

M L Epstein

Publications and source records attributed to M L Epstein.

At least 37 records · Page 2Linked to original sources

Failure of adenosine to terminate focal atrial tachycardia.

Adenosine has proven effectiveness in the diagnosis and treatment of a variety of tachycardias with both normal and widened QRS complexes in children and adults. Its effectiveness is due to its depressant effects on atrioventricular node conduction. Adenosine might also be effective against automatic tachycardia due to spontaneous activation in partially depolarized cells. This report describes a patient presenting with tachycardia with normal QRS complexes. While the adenosine did not restore sinus rhythm, it did disclose the mechanism of the arrhythmia. Since other investigators have reported successful interruption of automatic atrial tachycardia, this case suggests that automatic atrial tachyarrhythmia may be due to more than one mechanism.

Adenosine↗

Effect of growth and maturation in a hypoxic environment on maximum coronary flow rates of isolated rabbit hearts.

This study was designed to determine the effect of growth and maturation of rabbits in a hypoxic (H) environment on the ability to perfuse myocardium. Rabbits were raised in either a normoxic (N) (PO2 = 19.7 kPa or 149 torr) or an H environment (PO2 = 8.6 kPa or 65 +/- 3 mm Hg) and were studied at ages 5 wk (immature) and 12 wk (mature). Coronary flow (CF) was measured at baseline, during infusion of a maximally dilating concentration of adenosine (A), and at peak reactive hyperemic response to transient inflow occlusion in an isolated, non-blood-perfused heart preparation. Hearts were unloaded, paced at a constant rate (200 beats/min), and perfused at a constant inflow pressure (50 mm Hg). Regional CF was measured, using microspheres, in right ventricular, left ventricular, and atrial cardiac segments during vasodilation with A. H rabbits developed right ventricular but not left ventricular segment hypertrophy/hyperplasia. CF was greater in immature than mature hearts and higher in H than N hearts during baseline, vasodilation with A, and at peak reactive hyperemia (two-way analysis of variance, p < or = 0.05). Regional CF during vasodilation with A was greater in immature than mature hearts, in both right and left ventricular segments, and higher in H than N hearts in all cardiac segments (two-way analysis of variance, p < or = 0.05). Differences in total and regional CF between H and N hearts were present at both study ages (t test, p < or = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Development and birthdates of vasoactive intestinal peptide immunoreactive neurons in the chick proventriculus.

To gain insight into the mechanisms regulating expression of transmitter phenotypes in the enteric nervous system, we have studied the development and birthdate of vasoactive intestinal peptide immunoreactive (VIP-IR) myenteric neurons in the chicken proventriculus (secretory portion of the avian stomach) by a combination of immunocytochemistry and radioautography. The appearance and numbers of VIP-IR neurons in whole mounts of the myenteric plexus from chick embryos and chickens were examined. We found that VIP-IR neurons first appeared at embryonic day (E) 5.5-6.5 in the distal part of the proventriculus. At E7.5, VIP-IR neurons were found singly, in pairs, or in small groups, which together with unlabeled cells formed primitive myenteric ganglia. VIP-IR fibers were found within the developing fiber tracts which connected the ganglia. The number of VIP-IR neurons was found to be maximum in the E15.5 embryo and to decline to 68% of maximum in the 4 week old chicken. Birthdate studies were performed by application of either single pulses or cumulative doses of [3H]-thymidine to embryos between E3 and E14. Whole mounts of the myenteric plexus from the proventriculus of these embryos were immunostained for VIP at E10 or E17. The whole mounts were subsequently sectioned and processed for radioautography. We found that VIP-IR myenteric neurons were born between E3 and E10 with a peak at E7. Most cells underwent terminal division between E5 and E9. These data will be useful in determining the time and conditions when cells make decisions about transmitter phenotypes.

Aging↗

Reinnervation of villi of rat jejunum following severe mucosal damage.

We studied the time course of the regeneration of the jejunal mucosa of the rat after it was damaged by exposure to the surfactant, benzalkonium chloride. We placed particular emphasis on assessing the morphology of the nerve fibers within the villi during and after regeneration. The application of benzalkonium chloride resulted in virtually complete loss of villi within the treated segment; however, the crypts were only partially damaged. The mucosa began to regenerate within 6 hr of the insult. The villus lengths and crypt depths returned to pretreatment values within two to four days. The mucosal innervation was assessed through immunohistochemistry for vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), and neuron-specific enolase (NSE). At all stages of regeneration, VIP, NPY, and NSE immunopositive fibers within the lamina propria extended to the tips of the villi. The density of the immunopositive fibers in the lamina propria at four days after mucosal insult was similar to that in control tissues regardless of the neuronal marker visualized. We conclude that the nerve fibers innervating the small intestinal mucosa grow at a rate of approximately 100 microns/day and that the entire length of each villus contains nerve fibers throughout the regeneration process. The innervation of the regenerated mucosa appears identical to that of control mucosa.

Animals↗

Adenosine-induced atrioventricular block: a rapid and reliable method to assess surgical and radiofrequency catheter ablation of accessory atrioventricular pathways.

Adenosine has been shown to inhibit anterograde and retrograde conduction through the atrioventricular (AV) node while having little or no effect on accessory pathway conduction. Its rapid onset of action and short half-life make it particularly suitable for repetitive measurements. In this study, the utility of adenosine was tested in assessing completeness of accessory pathway ablation. Sixteen patients with an accessory pathway were studied (eight surgical ablations, eight catheter ablations with radiofrequency energy). Before ablation, no accessory pathway was sensitive to adenosine. Twelve patients with pre-excitation showed high grade AV node block with maximal pre-excitation on the administration of adenosine during atrial pacing. Four patients with a concealed accessory pathway demonstrated high grade AV block without evidence of latent anterograde accessory pathway conduction. Preablation ventriculoatrial (VA) block was not observed in any of the 16 patients in response to adenosine during ventricular pacing. Immediately after accessory pathway ablation, all patients developed AV and VA block with the administration of adenosine during atrial and ventricular pacing, respectively. These findings were confirmed during follow-up study 1 week later. Atrioventricular block during atrial and ventricular pacing with adenosine affords a reliable and immediate assessment of successful pathway ablation.

Adenosine↗

Appearance of somatostatin and vasoactive intestinal peptide along the developing chicken gut.

The appearance of somatostatin (SOM)-immunoreactive (IR) and vasoactive intestinal peptide (VIP)-IR neurons in different regions of the embryonic chicken gut was studied by immunostaining wholemounts. The patterns of expression of these peptides in myenteric neurons showed a number of similarities. Both peptides first appeared in the region of the proventriculus-gizzard: SOM at embryonic day (E)4, VIP at E5.5. At later times both peptides were found in positions both rostral and caudal to the gizzard. Both peptides appeared independently in cells at a second site, the cecum of the hindgut: SOM was observed at E6.5 and VIP at E7.5. VIP-IR and SOM-IR cells appear throughout the cecum, then in the rectum, and finally in the ileum. Differences in the patterns of expression were also found. SOM- and VIP-IR neurons appeared at different times along the length of the gut. VIP-IR cells populated the entire gut by E11.5, whereas SOM-IR cells were not present throughout the gut until E13.5. SOM-IR cells appeared in the terminal part of the ganglion of Remak at E4.0. At E6 these SOM-IR cells sent fibers into the wall of the hindgut and later into the midgut. No VIP-IR cells were found in the ganglion of Remak. These findings suggest that neural crest-derived cells first express SOM- and VIP-IR in particular regions of the gut, namely, the proventriculus-gizzard and the cecum. Certain conditions must exist at these sites which favor the expression of these neuropeptides by neural crest-derived cells. The observation of SOM- and VIP-IR cells in the cecum at a stage of development before cells are seen in the ileum supports the concept that sacral neural crest cells contribute precursors for enteric neurons of the avian hindgut.

Animals↗

Formation of ganglia in the gut of the chick embryo.

We have examined the formation of myenteric ganglia in the developing avian enteric nervous system. The monoclonal antibody HNK-1 was used to identify neural-crest-derived cells in whole mounts of fore- and midgut of chick embryos. We find that the crest-derived cells extend processes to their neighbors and form a complex network in the wall of the gut. Formation of this network is an unusual behavior of crest-derived cells and suggests the gut microenvironment is critical to this behavior. This cellular network disappears after ablation of the vagal neural crest, indicating the HNK-1-stained cellular network arises from crest-derived cells. The network is found in the gut wall before the vagal nerve fibers are present. This network is first found in the primordium of the proventriculus, distal to the evagination of the lung buds, and progresses just proximal to the yolk stalk at embryonic day (E) 3.5 and almost to the ileocecal junction at E5.5. The number of cells and the complexity of the network decrease in a rostral-caudal direction down the length of the gut at these stages. The leading edge of the network consists of cells serially arranged in longitudinally running strands. The organization of the network changes with increasing embryonic age; we have focused on network changes in the proventriculus. In the primordium of the proventriculus at E3.5, the network consists of a cluster of one or two adjacent crest-derived cells, which extend processes to a number of neighboring crest-derived cells. At E5.5 large increases in the number of cells per cluster and in the length of cellular connectives between clusters are apparent. At E6.5 a crude meshwork of clusters is seen. At E10.5 the arrangement of cell clusters resembles the pattern of ganglia found in the adult myenteric plexus. This network may provide the environmental cues for the differentiation of enteric neurons and a framework for the pattern of ganglia found in the adult enteric nervous system.

Animals↗

Anomalous systemic venous to left atrial connection in tricuspid atresia with severely restrictive interatrial communication.

An adequate interatrial communication is necessary to accommodate right atrial output in patients with tricuspid atresia. We report a patient with a tiny opening in the midportion of the atrial septum, who was found to have an anomalous systemic venous to left atrial communication. This channel was not evident on noninvasive testing, but would likely have caused persistent desaturation following a Fontan procedure had it not been detected. In patients with restrictive interatrial communications, an angiogram of the right atrium may reveal similar anomalous channels.

Abnormalities, Multiple↗

Effects of chronic hypoxia during maturation on the negative chronotropic effect of [H+] on the rabbit sino-atrial node.

Previous studies in our laboratory have shown an effect of 12 weeks of hypoxia on the electrophysiology of the heart. This study was designed to determine the effects of hypoxia for shorter periods (1, 2, 3 and 6 weeks) on the neonatal heart as well as the chronotropic effects of [H+] on sino-atrial automaticity. Rabbits (2 days of age) were raised for 1, 2, 3 or 6 weeks in either a normal or hypoxic environment. At the end of 1, 2, 3 or 6 weeks, they were killed and studied using an isolated sino-atrial tissue preparation and standard microelectrode techniques. Measurements of hematocrit, ventricular weight and ventricular total protein were made. Right ventricular hypertrophy appeared at 2 and 3 weeks in the hypoxic hearts. There was no difference in left ventricular weight or total protein between normal and hypoxic groups over the time studied. Both the basal and maximal (isoproterenol stimulated) spontaneous rates decreased with age. The baseline and maximal rates from hypoxic rabbits were significantly less than those from normal rabbits at 3 and 6 weeks (p less than 0.05). The net negative chronotropic effect of elevated [H+] was more pronounced in the hypoxic than the normal preparations at 3 and 6 weeks. In summary, neonates raised in hypoxia for as short a period as 3 weeks show right ventricular hypertrophy and a decrease in sino-atrial automaticity. The net negative chronotropic effect of [H+] is enhanced with development and chronic hypoxia.

Acidosis↗

Feasibility of reversible pulmonary artery banding: early results and intermediate-term follow-up.

Development of a reversible pulmonary artery band might obviate the need for a second cardiac surgical procedure in children with some forms of congenital heart disease. We evaluated a segmented Silastic-coated Dacron mesh band 2 to 4 mm wide sewn together with absorbable 2-0 polydioxanone suture for use as a reversible pulmonary artery band. Nine puppies 6 to 8 weeks old (mean weight, 5.8 kg) underwent placement of this pulmonary artery band. All survived the operation with a mean initial systolic gradient of 6.5 +/- 1.6 mm Hg and underwent cardiac catheterization at monthly intervals for 3 months. Two puppies died of right ventricular failure. The remaining puppies underwent balloon angioplasty with balloons 20 to 25 mm in diameter. No complications resulted from balloon angioplasty, but 1 puppy died 24 hours later of unidentified causes. Balloon angioplasty decreased the mean gradient from 46.7 +/- 6.8 mm Hg to 6.7 +/- 2.6 mm Hg. Angiography showed an increase in mean diameter of the site of the pulmonary artery band from 5.2 +/- 1.0 to 10.8 +/- 1.7 mm Hg. There was no evidence of vessel injury on angiograms. Fourteen months after balloon angioplasty, the mean gradient was 22.3 +/- 17.0 mm Hg. Our data demonstrate that a functionally reversible pulmonary artery band constructed of segmented Silastic-coated Dacron mesh and 2-0 polydioxanone suture is feasible.

Angioplasty, Balloon↗

Differential development of cholinergic neurons from cranial and trunk neural crest cells in vitro.

Several studies have suggested that the development of cholinergic properties in cranial parasympathetic neurons is determined by these cells' axial level of origin in the neural crest. All cranial parasympathetic neurons normally derive from cranial neural crest. Trunk neural crest cells give rise to sympathetic neurons, most of which are noradrenergic. To determine if there is an intrinsic difference in the ability of cranial and trunk neural crest cells to form cholinergic neurons, we have compared the development of choline acetyltransferase (ChAT)-immunoreactive cells in explants of quail cranial and trunk neural crest in vitro. Both cranial and trunk neural crest explants gave rise to ChAT-immunoreactive cells in vitro. In both types of cultures, some of the ChAT-positive cells also expressed immunoreactivity for the catecholamine synthetic enzyme tyrosine hydroxylase. However, several differences were seen between cranial and trunk cultures. First, ChAT-immunoreactive cells appeared two days earlier in cranial than in trunk cultures. Second, cranial cultures contained a higher proportion of ChAT-immunoreactive cells. Finally, a subpopulation of the ChAT-immunoreactive cells in cranial cultures exhibited neuronal traits, including neurofilament immunoreactivity. In contrast, neurofilament-immunoreactive cells were not seen in trunk cultures. These results suggest that premigratory cranial and trunk neural crest cells differ in their ability to form cholinergic neurons.

Animals↗

The myenteric plexus regulates cell growth in rat jejunum.

The roles of the myenteric and extrinsic nerves in the control of proliferation and cell growth in the rat jejunum were studied. The myenteric plexus and/or the extrinsic nerves in a segment of rat jejunum were ablated by serosal application of the surfactant benzyldimethyltetradecylammonium chloride or by crushing the nerves passing through the mesentery, respectively. Ablation of both myenteric and extrinsic nerves, but not the extrinsic nerves alone, resulted in a significant increase in the mitotic rate of the crypt-epithelial cells and in the size of VIP-immunoreactive neurons in the submucosal plexus. The increased mitotic rate was correlated with an increase in the weight of the mucosa per unit length of gut and in the villus length and crypt depth. Neither extrinsic denervation alone nor serosal application of saline had any effect on these parameters. Our results suggest that the myenteric plexus is able to influence the rate of cell proliferation and cell growth in the rat jejunum.

Animals↗

Correction of reentrant atrioventricular tachycardia by surgical ablation of accessory pathways.

Patients with reentrant atrioventricular (AV) tachycardia have an accessory connection in addition to the normal conduction pathway, AV node and His-Purkinje system. This pathway predisposes some patients to recurrent, disabling supraventricular tachyarrhythmias. Although it is found with other associated cardiac conditions, most patients are healthy with no underlying structural heart disease. Interest has developed in surgically dividing the accessory pathway in patients with arrhythmias poorly controlled with medications or at risk for potentially fatal tachyarrhythmias. Surgery is safe and effective and should be considered for patients with rapid AV conduction during atrial fibrillation, those refractory to pharmacologic therapy, and young patients who otherwise would require lifelong antiarrhythmic therapy. This report describes surgical correction of reentrant AV tachycardia in five patients ranging in age from six months to 23 years.

Adolescent↗

Effect of chronic hypoxia on cardiac beta-adrenergic and muscarinic receptors during maturation.

The effect of hypoxia on cardiac beta-adrenergic and muscarinic receptors during the first 3 weeks of postnatal development was determined in the rabbit. After the first week of postnatal exposure to hypoxia, there was no change in the ventricular content of beta-adrenergic receptors. However, after 2 weeks of hypoxia, there was a 24% decrease in the receptor content of the left ventricle with no change in the right ventricle. At the end of 3 weeks exposure to hypoxia, the receptor content had decreased by 31% and 32% in the right and left ventricle, respectively. In control animals, there was no alteration in the beta-adrenergic receptor content of either ventricle over the 3 week period. In contrast to the beta-adrenergic receptor, there was no hypoxia-associated alteration in the muscarinic receptor content of either ventricle during the 3 weeks of postnatal study. The data suggest that hypoxia during the first 3 weeks of postnatal development in the rabbit induces alterations in the cardiac beta-adrenergic receptor with no effect on the development of the cholinergic muscarinic receptor.

Animals↗

Hyperplasia of jejunal smooth muscle in the myenterically denervated rat.

Application of a cationic surfactant, benzalkonium chloride, to the serosa of rat jejunum results in an increase in thickness of both longitudinal and circular smooth muscle layers. The increase in thickness is due primarily to an increase in the number of smooth muscle cells (hyperplasia). Little cellular hypertrophy was observed. The time sequence of surfactant-induced effects on the muscle layers was determined. Within 24 h, total destruction of the longitudinal muscle and partial destruction of the circular muscle was evident. The myenteric plexus was also necrotic; however, the submucosal plexus remained intact. By 48 h after surfactant treatment, the smooth muscle cells remaining in the circular muscle layer had begun to divide, as indicated by the presence of mitotic figures and incorporation of 3H-thymidine. A repopulation of the longitudinal muscle layer began at this time, apparently the result of migration of cells arising in the circular muscle layer. By 5 days post-treatment, both muscle layers had regenerated to their original states. The myenteric plexus was totally absent. The denervated smooth muscle cells proceeded to divide until approximately day 15, resulting in hyperplasia of both muscle layers. Between 15 and 105 days, the number of muscle cells in the circular layer progressively declined, eventually returned to the value seen in control tissue. In contrast, the number of smooth muscle cells in the longitudinal layer remained elevated through the period of study (165 days). We hypothesize that the smooth muscle hyperplasia observed after serosal benzalkonium chloride application results from loss of the myenteric nerves.

Animals↗

Cholinergic neurons of the chicken ciliary ganglion contain somatostatin.

Somatostatin immunoreactivity was studied in the avian ciliary ganglion by immunocytochemistry and radioimmunoassay. Immunoreactivity was localized to small diameter cell bodies of neurons from embryos, newly-hatched and adult preparations. Immunostaining of ganglia with a mixture of antisera to substance P and monoclonal antibody to somatostatin indicated that a number of somatostatin-immunoreactive neurons were surrounded by substance P-immunoreactive boutons, which characteristically terminate on choroidal neurons. Staining with a mixture of antisera to choline acetyltransferase and antibody to somatostatin showed that the somatostatin-immunoreactive neurons were less intensely-stained for choline acetyltransferase than were the neurons lacking somatostatin immunoreactivity. Bundles of nerve fibers showing somatostatin and choline acetyltransferase immunoreactivity were found in the choroid layers of the eye. Radioimmunoassay indicated the presence of somatostatin immunoreactivity in both chick and quail ganglia; the somatostatin immunoreactivity eluted from high pressure liquid chromatography in the same positions as authentic somatostatin 14 and 28. These results show that somatostatin is contained in cholinergic choroidal neurons in the chick and quail ciliary ganglion.

Animals↗

Localization of choline acetyltransferase-like immunoreactivity in the embryonic chick retina.

Putative sites of acetylcholine synthesis in the retina of the embryonic and posthatched chick were localized immunohistochemically with antisera to choline acetyltransferase; the resultant choline acetyltransferase-like immunoreactivity (ChAT-IR) was compared to demonstrated sites of acetyltransferase (AChE) activity, and changes were followed in localization during development. The results confirmed the early and rapid course of development of the chick's retinal cholinergic system described in previous biochemical and morphological studies. Immunoreactivity was first detected at embryonic day 6.5 in cells close to the retina's vitreal surface. By 8 days it was present in cells in two juxtaposed rows; by the ninth day the two rows were separated and immunoreactivity was evident in two subliminae of the inner plexiform layer. On the tenth day distribution was like that in the posthatched chicken, in type I cholinergic cells in the inner nuclear layer and in type II cells in the ganglion cell layer (Millar et al.: Neurosci. Lett. 61:311-316, '85), and similar to that of most vertebrates. Three days before hatching, a third population of weakly immunoreactive cells (type III cells) appeared within the inner nuclear layer. The onset of localizable ChAT-IR occurred in amacrine cells and in their processes, before the period of synaptogenesis. Acetylcholinesterase activity was localized at an earlier age than ChAT-IR, and at all ages was present in more cells. The results obtained support the view that "displaced" cholinergic amacrine cells begin to differentiate at the same time and in the same retinal region as type I cholinergic cells. Separation of the two groups is a consequence of the ramification of processes of amacrine and ganglion cells rather than a result of the secondary migration of cells between layers.

Acetylcholinesterase↗