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Biomedical subjects

J F Schlegel

Publications and source records attributed to J F Schlegel.

At least 19 recordsLinked to original sources
PubMed1993

Neuroregulation of a chemosensitive afferent system in the canine distal esophagus.

Systemic and local responses mediated by chemonociceptive receptors located in the mucosa of the canine distal esophagus were examined following stimulation with capsaicin (8-methyl-N-vanillyl-6-nonenamide). The neural pathways and neurotransmitters mediating these sensory responses were also investigated. Topical application of capsaicin solution to the distal esophageal mucosa produced significant increases in lower esophageal sphincter pressure (LESP), mean arterial pressure (MAP), pulse rate (PR), and respiratory rate (RR) (P < 0.01). Pretreatment with tetrodotoxin completely abolished this reflex activity. Following truncal vagotomy and pyloroplasty, topical capsaicin application produced an increase in LESP, but the increases in MAP, PR, and RR were blocked. The initial increase in LESP was blocked by hexamethonium, atropine, and 4-diphenylacetoxy-N-methylpiperidine, but was not inhibited by phentolamine. Excitatory cardiovascular responses were inhibited by hexamethonium. Administration of a Substance P antagonist attenuated both local and systemic responses. These studies suggest that the vagus nerves serve as the primary afferent pathways through which chemonociceptive esophageal stimuli can induce cardiovascular and respiratory reflex excitation. The increase in lower esophageal sphincter pressure in response to mucosal capsaicin stimulation is mediated via an intrinsic neural pathway that functions independently of vagal innervation, but is dependent on both cholinergic ganglionic neurotransmission and muscarinic type 2 smooth muscle receptor excitation. Substance P appears to play a role in primary sensory afferents as a chemonociceptive neurotransmitter in the canine distal esophagus.

Afferent Pathways↗
PubMed1993

Functional and morphological characteristics of neuronal substance P in the canine gastroesophageal junction.

The specific functions of the numerous substance P (SP) nerve fibers present within the gastrointestinal tract are not clearly defined. This study examines both functional aspects and distribution of immunoreactive SP (IR-SP) in the canine gastroesophageal junctional (GEJ) region. Lower esophageal sphincter pressure (LESP), mean arterial pressure (MAP), pulse rate (PR), and respiratory rate (RR) were monitored before and after topical application of 2 ml capsaicin (8-methyl-N-vanillyl-6-nonenamide) to the distal esophageal mucosa of anesthetized dogs. Animals then underwent a capsaicin desensitization protocol over a 12-day period. The responses of monitored variables were compared on Day 1 and Day 12 of repetitive capsaicin application. Immunohistochemistry and radioimmunoassay (RIA) were performed on GEJ segments to study the distribution and content of IR-SP in both control (untreated) and capsaicin-treated dogs. The IR-SP was extracted from tissue for RIA and analysis by reverse-phase high-performance liquid chromatography (HPLC). On Day 1, a 2-ml capsaicin application stimulated increases in LESP (44.3 +/- 7.8 cm H2O; P < 0.05), MAP (48 +/- 8.7 mm Hg; P < 0.05), PR (52.6 +/- 20.5 beats/min; P < 0.05), and RR (26.3 +/- 15.6 breaths/min; P > 0.2). No response was observed on Day 12 of treatment. This was accompanied by a 43.3% decrease of IR-SP content in the mucosa of the distal esophagus of desensitized animals. Capsaicin applied at greater concentrations on Day 12 stimulated a return of responses (P < 0.05). Ganglia, cell bodies, nerve fascicles, and neurites stained positively for IR-SP. IR-SP content was markedly higher in esophageal mucosa than in gastric mucosa (P < 0.05). The authenticity of the IR-SP molecule was confirmed by elution time on HPLC. In conclusion, repetitive capsaicin application induced a state of homologous desensitization which was accompanied by a partial depletion of mucosal SP. The GEJ region contains a high SP content with a broad neural distribution. These findings are consistent with the hypothesis that SP may act as a neurotransmitter for chemonociceptive stimuli in the canine distal esophagus.

Animals↗
PubMed1991

Tachykinins in the canine gastroesophageal junction.

Lower esophageal sphincter (LES) effects produced by the mammalian tachykinins were evaluated in anesthetized dogs. The distribution and content of substance P (SP) and neurokinin A (NKA) in the region of the canine gastroesophageal junction was also studied. SP and NKA stimulated a linear dose-dependent contraction of the LES after intra-arterial administration. Neurokinin B (NKB) failed to stimulate an increase in LES pressure (LESP). SP was characterized by an immediate but short-lived contraction followed by a period of relaxation. NKA stimulated a potent LES contraction that was slow in onset but long-lasting. On an equimolar basis, both SP and NKA were approximately 100 times more potent LES stimulants than bethanechol or phenylephrine. Pretreatment with atropine (muscarinic blockade) or tetrodotoxin (neural blockade) inhibited the effect produced by SP. NKA appeared to stimulate LES contraction independent of neural or cholinergic mechanisms. Radioimmunoassay revealed a regional variation in tachykinin content in the gastroesophageal junction. Ganglia, cell bodies, nerve fascicles, and neurites stained specifically for both SP and NKA. The variable effects, potencies, and mechanisms of action observed in this study suggest the presence of specific tachykinin receptor subtypes in the gastroesophageal junction. Both SP and NKA were found to have a broad neural distribution in this region. These findings suggest that the tachykinins may play an important role in neuroregulation of LES smooth muscle.

Animals↗
PubMed1989

Mechanisms of increased lower esophageal sphincter pressure following intraduodenal peptone infusion in dogs.

Peptone perfusion of the excluded duodenum in dogs is associated with an increase in lower esophageal sphincter pressure (LESP). This study investigates the role of cholinergic, adrenergic, and hormonal mediators in the response of the LES to intraduodenal peptone infusion. Adult dogs underwent duodenal exclusion via a Roux-en-Y pylorojejunostomy with formation of a mucocutaneous fistula. Manometric measurements of LESP and radioimmunoassay determinations of gastrin and pancreatic polypeptide (PP) blood levels were made at rest and at 15-min intervals following peptone infusion of the excluded duodenum. In control experiments, peptone infusion resulted in an increase in mean LESP at all time intervals (P less than 0.05). PP blood levels increased significantly, while gastrin levels remained unchanged. Both truncal vagotomy and pretreatment with atropine blocked the changes in LESP. PP release in response to peptone was accentuated in vagotomized dogs, while atropine suppressed the release of PP following peptone infusion. Treatment with 6-hydroxydopamine did not affect the increase in either LESP or PP blood levels observed in controls. Intravenous somatostatin suppressed the release of PP following intraduodenal peptone, but did not block the lower esophageal sphincter response. This data indicates that the increase in LESP seen following intraduodenal peptone infusion is centrally mediated and dependent on vagal innervation and cholinergic neurotransmission.

Animals↗
PubMed1989

The mechanism of acid-induced increases in canine lower esophageal sphincter pressure.

Acidification of the gastric cardia has been shown to increase lower esophageal sphincter pressure (LESP). The mechanism by which this phenomenon occurs remains unknown. This study was undertaken to examine the effect and mechanism of action of proximal gastric acidification on LESP in the dog model. In long-term studies, acidification resulted in a significant increase in mean LESP (23.2 cm H2O). Pretreatment with either topical lidocaine or subcutaneous atropine blocked the sphincteric response to acidification. Neither truncal vagotomy and pyloroplasty, proximal gastric vagotomy, antral vagotomy and pyloroplasty, nor circumferential gastric myotomy significantly altered the sphincteric response to acid. Pretreatment with 6-hydroxydopamine or somatostatin also failed to alter the increase in LESP in response to acid. In short-term studies, after gastric transection 5 cm distal to the gastroesophageal junction, acidification of a vagally innervated distal gastric pouch produced a slight decrease in LESP, whereas acidification of the proximal (orad) section of gastric mucosa still resulted in a significant increase in LESP. These studies suggest that the increase in LESP observed with acidification of the gastric cardia is a local mechanism mediated by an intrinsic neural pathway dependent on cholinergic neurotransmission. This phenomenon of local reflex excitation may be another contributing mechanism to the barrier against gastroesophageal reflux.

Animals↗
PubMed1987

The effect of preoperative internal and external biliary drainage on mortality of jaundiced rats.

Mortality following abdominal infection induced by cecal ligation and puncture was studied in rats with obstructive jaundice and after relief of the obstruction by preoperative internal or external biliary drainage. Four groups of adult Sprague-Dawley rats were used: common bile duct ligation (BDL), BDL followed by internal drainage after two weeks, BDL followed by external drainage after two weeks, and sham operation. The serum bilirubin concentration was significantly increased in the BDL group and returned to normal following internal and external drainage. Mortality in the sham group was 16.5% and increased to 83.3% following BDL, but it decreased significantly (25%) to near-normal values after preoperative internal drainage. However, after external drainage no significant reduction in mortality (63%) was found. These findings confirm the poor results of preoperative external drainage in previous studies and establish the efficacy of internal biliary drainage in a well-controlled experimental model that has to be evaluated in the clinical situation.

Animals↗
PubMed1986

Effect of feeding on myoelectric activity of the sphincter of Oddi and the gastrointestinal tract in the opossum.

The effect of different foods on the myoelectric activity of the sphincter of Oddi and gastrointestinal tract was evaluated in the opossum. Gallbladder pressure was also recorded. Feeding fat and mixed food resulted in the greatest incidence of spike activity in the duodenum and jejunum, followed by protein. The lowest incidence of slow waves with spikes in the duodenum and jejunum followed feeding of carbohydrates (P less than 0.01). Likewise, the lowest spike activity in the sphincter of Oddi was observed after carbohydrate feeding (P less than 0.05). There was no significant difference in the incidence of spike potentials in the sphincter of Oddi when fat, protein, or mixed food was fed. No significant change in gallbladder pressure during fasting and following feeding of different aliments was observed. We concluded that there is a correlation between the frequency of spike potentials in the sphincter of Oddi and in the small bowel following feeding. The duration of the fed pattern for each type of food correlated with the number of spikes in the sphincter of Oddi and gastrointestinal tract.

Ampulla of Vater↗
PubMed1986

Endotoxemia after relief of biliary obstruction by internal and external drainage in rats.

Systemic and portal endotoxemia were studied in rats with biliary obstruction and after relief of the obstruction by internal and external drainage. Endotoxemia was increased after bile duct ligation (p less than 0.001) compared with control values. The incidence of systemic and portal endotoxemia was significantly reduced after internal drainage (p less than 0.001). A significantly higher incidence of portal (86 percent) and systemic (57 percent) endotoxemia, however, was found after external drainage. The persistence of endotoxemia after external drainage, when serum bilirubin levels returned to normal units, indicates that bile flow is important in controlling endotoxemia during preoperative biliary drainage. These results suggest that the systemic endotoxemia observed after relief of obstruction by external drainage may contribute to the increased mortality, as found in previous rat studies. This observation may contribute to an understanding of why patients with preoperative external drainage of biliary obstruction have a higher incidence of septic complications.

Animals↗
PubMed1986

Effect of 16,16-dimethyl prostaglandin E2 on the myoelectric activity of the gastrointestinal tract of the opossum.

Myoelectric recordings of the opossum gastrointestinal tract were performed during continuous infusion of 16,16-dimethyl prostaglandin E2 at 0.1, 1, 2 and 5 micrograms/kg X h. Continuous administration of prostaglandin caused a dose-dependent reduction of the duration of the migrating myoelectric complex cycle and an increase in the velocity of phase III migration from the duodenum to the terminal ileum. The reduction of the migrating myoelectric complex cycle was due to a shortening of the duration of both phase I and II. Bolus administration of 16,16-dimethyl prostaglandin E2 caused intense spike activity for 2-4 min in all recording sites simultaneously. Administration of indomethacin did not change the myoelectric activity of the gastrointestinal tract. Infusion of prostaglandin E2 caused diarrhoea in eight of forty experiments. These changes in gastrointestinal motility may be important contributory factors in the pathogenesis of prostaglandin-induced diarrhoea.

16,16-Dimethylprostaglandin E2↗
PubMed1986

APhA: on the move.

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Societies, Pharmaceutical↗
PubMed1984

The effect of celiac and superior mesenteric ganglionectomy on the canine gastric mucosal barrier.

The role of the sympathetic nervous system in gastric function remains poorly understood. This study was designed to evaluate the effect of celiac and superior mesenteric ganglionectomy on gastric mucosal barrier function. Four dogs with Pavlov-type pouches were studied. In the preganglionectomy phase, the pouch gastric mucosa was challenged with progressively higher concentrations of known damaging agents, ethanol and taurocholic acid. Mucosal integrity was studied by measuring ionic fluxes (H+, Na+, K+, Cl-) and transmucosal electrical potential difference (PD). Celiac and superior mesenteric ganglionectomy was then performed and after adequate recovery, the postganglionectomy phase of the study was done challenging the mucosa with the same damaging agents at the same concentrations used in the preganglionectomy study. The major alterations which occurred postganglionectomy were primarily motility-related and little evidence of altered gastric mucosal barrier permeability was detected. Specifically, all four animals developed an intractable diarrhea postganglionectomy which resulted in a 20% weight loss over 4-6 weeks. In contrast, there was no significant difference in H+ loss from and Na+/K+ gain to the pouches when the pre- and postganglionectomy fluxes were compared. Similarly, after challenge with damaging agents, PD changes in the pre- and postganglionectomy were not significantly different.

Animals↗