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Laparoscopic heller myotomy with fundoplication: Potential first line treatment for achalasia
Motility and Nerve-Gut Interactions A837
April 1998 uncovered a contraction that started with the onset of EFS. This contraction was abolished by atropine. Atropine alone had little effect on the timing or amplitude of the off response. ODQ did not inhibit the longitudinal muscle contraction. Discussion: In these studies, inhibition of cGMP production produced effects analogous to those of inhibitors of NO synthase. This suggests that the control of esophageal motor function by NO nerves is mediated by cGMP. These studies also indicate that a functional cholinergic innervation is present in the distal esophagus and that it may play a role in setting the timing of peristalsis. These studies were supported by a VA Merit Grant. • G3434 LAPAROSCOPIC IIELLER MYOTOMY WITH FUNDOPLICATION: POTENTIAL FIRST LINE TREATMENT FOR ACRALASIA. V. Shayani, K. Bruninga, A. Keshavarzian. Depts. of Surgery and Med., Loyola Uni. Med. Sch., Maywood, IL. Background: Pneumatic balloon dilatation and endoscopic injection of botulinum toxin are effective and widely practiced first line management of achalasia. They however may be associated with a significant incidence of complications. Many patients (pts) may also experience recurrent symptoms which require repeated interventions. Surgical myotomy, the alternative treatment for achalasia, although highly effective in the long term, is often associated with significant peri-operative morbidity. As a result, myotomy is considered by many only in those pts who have failed medical therapy. The application of video-assisted technology to surgical myotomy may limit postoperative morbidity and render surgical therapy as a first line treatment for achalasia. Methods: Between October 1996 and November 1997, 11 pts (mean age 44) with documented achalasia [table] underwent laparoscopic Heller myotomy with fundoplication with follow-up ranging from 1 to 13 months. Three of the 11 pts underwent surgical myotomy as their first therapeutic intervention. 10 pts underwent Toupet (posterior 270 °) fundoplication and 1 pt underwent (anterior) Dor fundoplication. Results: All operations were completed laparoscopically. There were no peri-operative deaths. None of the pts required blood transfusion. Ten of the 11 p t s (6 males/5 females) were fed within 24 hours and 9 were discharged from the hospital within 48 hours. One operative esophageal tear was encountered and was repaired laparoscopically. This pt was fed in 3 days and discharged in 4 days. None of the pts have required a repeat operative or endoscopic procedure. None of the pts have reported symptoms of reflux or required treatment with antireflux medications. 2 pts had prolonged but self-resolving dysphagia (up to 4 weeks), one of whom required readmission to the hospital for food impaction.
Duration of symptoms (years) mean: 6 range: 0.3-30
Diagnostic work up
Presurgical treatment
EGD: 11 UGI: 11 Manometry: 9
Balloon Dilatation Single: 1 Multiple: 6 Botulinum toxim 2 None: 3
Postoperative length of stay (days) Mean: 2.4 Range: 2-4
Conclusions: Laparoscopic Heller myotomy with fundoplication is an effective and safe method of treatment for achalasia. It can be performed with minimal peri-operative morbidity, and may be considered as the first line of treatment in pts who are good surgical candidates. G3435 INFLAMMATORY MODULATION OF M 2 RECEPTOR COUPLING TO ADENYLATE CYCLASE IN CANINE ILEAL LONGITUDINAL AND CIRCULAR MUSCLE CELLS. X-Z Shi and S.K. Sarna, Depts. of Surg. and Physiol., Medical College of Wisconsin and Zablocki VAMC, Milwaukee, WI. M 2 muscarinic receptors are coupled to Gt protein whose activation decreases adenylate cyclase activity. The aim of this study was to determine whether this signaling pathway is modulated by inflammation in the ileal longitudinal and circular muscle ceils. Circular but not longitudinal muscle contractility is depressed during acetic acid-induced ileal inflammation. Methods: Dog ileal longitudinal and circular muscle strips (2 x 2 mm) were incubated in 100 ~M IBMX for 20 min at 37" C. Forskolin (10 laM) was used to activate adenylate cyclase for 10 min. The decrease of adenylate cyclase activity by M2 receptor activation was determined by incubating the muscle strips with 10 laM methacholine for 1 min prior to their incubation with forskolin. Reactions were terminated by adding 2 volumes of ice-cold 6% trichloroacetic acid. cAMP levels were determined by the competitive protein binding assay (Amersham). Ileal inflammation was induced by a series of three mucosal exposures to ethanol and acetic acid. Results: The basal cAMP levels were not different between the normal longitudinal and circular muscle tissue (338 - 80 vs 278 -+ 75 pmol / mg protein, n = 4 resp.). Ileal inflammation did not alter the basic cAMP levels in the two muscle layers (321 + 55 and 301-+ 55 pmol / mg protein resp). Forskolin (10 ~aM) increased cAMP production 5.3 - 0.5 and 5.2 +- 1.1-fold over basal levels in the two muscle Iayers. This increase was not significantly different from that induced in the inflamed tissue, 6.9 +--1.0 and 6.9 _+1.6-fold respectively. Methacholine (10 laM) decreased cAMP production by 54-+ 5% in normal longitudinal muscle (p < .05) but by only 6.6 ± 8.3% (p > .05) in normal circular muscle.
Ileal inflammation did not affect the cAMP decrease bY methacholine in the longitudinal muscle (50 -+ 6%, p > .05, n = 4) but it significantly enhanced the cAMP decrease in the circular muscle (34 +-5%, p <.05, n = 4) Conclusions: In normal ileum, muscarinic receptor activation is coupled to adenylate cyclase in the longitudinal but not in the circular muscle. Inflammation does not alter this coupling in the longitudinal muscle but establishes it in the circular muscle. However, inflammation does not alter the basal levels of adenylate cyclase in the longitudinal or the circular muscle. The newly developed coupling between M2 receptors and adenylate cyclase may enable the circular muscle cells to contract partially in the inflamed state. • G3436 REDUCED Ca 2+ INFLUX CONTRIBUTES TO DECREASED CONTRACTILITY OF CIRCULAR MUSCLE CELLS IN COLONIC INFLAMMATION. X-Z. Shi and S.K. Sama. Depts. of Surgery and Physiology. Medical College of WI and Zablocki VAMC, Milwaukee, WI. Ca2÷ influx is an important source of Ca2÷ for the contractility of several types of smooth muscle cells. We investigated whether Ca2+ influx plays a role in the contraction of dispersed canine colonic circular muscle cells. If so, does a reduction in Ca2+ influx contribute to the suppression of circular muscle contractions during colonic inflammation? Methods: Healthy relaxed circular muscle cells were dispersed enzymatically from normal and inflamed proximal canine colons. Inflammation was induced by mucosal exposure to 75 mL of 95% ethanol and 20 mL of 60% acetic acid. Cell contractions were measured as percent decrease in length by scanning micrometry. The change in cytosolic free Ca2+concentration in response to agonists was measured in cell suspensions using the fluorescent dye Fura-2AM. Results: The lengths of dispersed circular smooth muscle cells obtained from the normal and the inflamed colon were not different from each other (97.8 -+4.2 and 96.9 -+4.6 Jam, n = 6 and 5 resp., p > 0.05). The dose response curves to muscarinic receptor agonist ACh (10-12 to 10,6 M), membrane depolarizer KCI (25 to 100 mM), and Ca2+ channel opener BAY K 8644 (10 -n to 10-5 M), were significantly suppressed in the inflamed cells. The maximum cell length shortening decreased from 25.4- 2.3% to 14.6-+ 3.6% for ACh at 10-8 M (n = 6 and 5, p <0.05) 25.2-+3.8% to 10.4-+5.2% for KC1 at 50 mM (n= 4 and 4, p <.05) and from 28.4 + 3.3% to 14.0 -+4.7% to BAY K 8644 at 10-6 M (n = 4 and 3, p <0.05). L- type Ca2+channel blocker, D600 (10-12to 10-6 M) dose-dependently decreased the response to ACh in normal and inflamed cells. The residual responses at the maximum dose of D600 were 8 -+3.4 and 5.1 _+ 1.2% in normal and inflamed cells. The ACh-induced decrease in length was completely blocked in Ca2+-free EGTA solution in normal and inflamed cells. The increase in cytosolic free Ca2+ in response to 50 mM KC1 was smaller in inflamed cells than in normal cells (61.7 vs 88%, n = 2). Conclusions: Ca2+ influx is required for the contraction of canine colonic circular muscle cells. Most influx occurs through L-type Cae÷ channels. Inflammation reduces the contractility of colonic circular smooth muscle cells. This may in part be due to a decrease in Ca2+ influx. • G3437 THE HERBAL MEDICINE, DAI-KENCHU-TO, STIMULATES UPPER GI MOTILITY IN CONSCIOUS DOGS VIA CHOLINERGIC AND 5-I-IT3 RECEPTORS. C. Shibata, I. Sasaki, H. Naito, N. Ohtani, T. Ueno, Y. Funayama, K. Fukushima, S. Matsuno. First Dept. of Surgery, Tohoku University School of Medicine, Sendal 980-8574, JAPAN. Dai-Kenchu-To (DKT), a herbal medicine consisting of 50 % Dried Ginger Rhizome (DGR), 30 % Ginseng Root (GR), and 20 % Zanthoxylum Fruit (ZF), is effective for reversing postoperative intestinal obstruction when administered into the stomach, but its mechanism of action is unknown. AIMS: To investigate effects of intragastric DKT, DGR, GR, and ZF on upper GI motility and the mechanism of action of DKT. METHODS: Six mongrel dogs were equipped with four strain gauge force transducers on the gastric body, antrum, duodenum, and jejunum to measure contractile activity of the circular muscle. DKT (1.5 g), ZF (1.0 g), GR (1.0 g), or DGR (1.0 g) dissolved in 50 ml 0.9 % NaC1 were administered into the gastric body through a silicone tube. The motor response obtained with 50 ml saline was used as a control. Effects of intravenous administration of atropine (muscarinic antagonist, 0.1 mg/kg + 0.1 mg/kg-h), hexamethonium (nicotinic antagonist, 5 mg/kg + 10 mg/kg-h), phentolamine (a-blocker, 0.5 mg/kg + 0.5 mg/kg-h), propranolol (13-blocker, 0.5 mg/kg + 0.5 mg/kg-h), or ondansetron (5-HT 3 antagonist, 0.3 mg/kg) on intragastric DKT-induced contractions was studied. Area under the contractile curve for 30 minutes after administration was measured and expressed as motor index (MI). RESULTS: Intragastric DKT increased MI (mean +-SEM), compared to control, in the antrum (1.9 _+0.4 vs. 0.6 - 0.1, p<0.05), duodenum (2.5 -+ 0.4 vs. 0.9 +-0.2, p<0.05), and jejunum (2.8 -+0.6 vs. 1.0 +-.0.2, p<0.05) but not in the gastric body (0.9 +_.0.2 vs. 0.8-+ 0.2). Intragastric DGR increased MI only in the gastric antrum. Intragastric GR had no effect on upper GI motility, whereas intragastric ZF increased MI in the duodenum and jejunum. Intragastric DKT-induced contractions were inhibited by atropine and ondansetron at all sites. Hexamethonium inhibited DKT-induced contractions in the duodenum and jejunum. Phentolamine and propranolol did not affect intragastric DKT-induced contractions at any site. CONCLUSIONS: Intragastric DKT stimulates upper gastrointestinal motility through cholinergic and 5-HT3 receptors. The different herb components of DKT stimulate motility at different sites; DGR mainly stimulated antral motility, whereas ZF stimulated duodenal and jejunal motility.
April 1998 uncovered a contraction that started with the onset of EFS. This contraction was abolished by atropine. Atropine alone had little effect on the timing or amplitude of the off response. ODQ did not inhibit the longitudinal muscle contraction. Discussion: In these studies, inhibition of cGMP production produced effects analogous to those of inhibitors of NO synthase. This suggests that the control of esophageal motor function by NO nerves is mediated by cGMP. These studies also indicate that a functional cholinergic innervation is present in the distal esophagus and that it may play a role in setting the timing of peristalsis. These studies were supported by a VA Merit Grant. • G3434 LAPAROSCOPIC IIELLER MYOTOMY WITH FUNDOPLICATION: POTENTIAL FIRST LINE TREATMENT FOR ACRALASIA. V. Shayani, K. Bruninga, A. Keshavarzian. Depts. of Surgery and Med., Loyola Uni. Med. Sch., Maywood, IL. Background: Pneumatic balloon dilatation and endoscopic injection of botulinum toxin are effective and widely practiced first line management of achalasia. They however may be associated with a significant incidence of complications. Many patients (pts) may also experience recurrent symptoms which require repeated interventions. Surgical myotomy, the alternative treatment for achalasia, although highly effective in the long term, is often associated with significant peri-operative morbidity. As a result, myotomy is considered by many only in those pts who have failed medical therapy. The application of video-assisted technology to surgical myotomy may limit postoperative morbidity and render surgical therapy as a first line treatment for achalasia. Methods: Between October 1996 and November 1997, 11 pts (mean age 44) with documented achalasia [table] underwent laparoscopic Heller myotomy with fundoplication with follow-up ranging from 1 to 13 months. Three of the 11 pts underwent surgical myotomy as their first therapeutic intervention. 10 pts underwent Toupet (posterior 270 °) fundoplication and 1 pt underwent (anterior) Dor fundoplication. Results: All operations were completed laparoscopically. There were no peri-operative deaths. None of the pts required blood transfusion. Ten of the 11 p t s (6 males/5 females) were fed within 24 hours and 9 were discharged from the hospital within 48 hours. One operative esophageal tear was encountered and was repaired laparoscopically. This pt was fed in 3 days and discharged in 4 days. None of the pts have required a repeat operative or endoscopic procedure. None of the pts have reported symptoms of reflux or required treatment with antireflux medications. 2 pts had prolonged but self-resolving dysphagia (up to 4 weeks), one of whom required readmission to the hospital for food impaction.
Duration of symptoms (years) mean: 6 range: 0.3-30
Diagnostic work up
Presurgical treatment
EGD: 11 UGI: 11 Manometry: 9
Balloon Dilatation Single: 1 Multiple: 6 Botulinum toxim 2 None: 3
Postoperative length of stay (days) Mean: 2.4 Range: 2-4
Conclusions: Laparoscopic Heller myotomy with fundoplication is an effective and safe method of treatment for achalasia. It can be performed with minimal peri-operative morbidity, and may be considered as the first line of treatment in pts who are good surgical candidates. G3435 INFLAMMATORY MODULATION OF M 2 RECEPTOR COUPLING TO ADENYLATE CYCLASE IN CANINE ILEAL LONGITUDINAL AND CIRCULAR MUSCLE CELLS. X-Z Shi and S.K. Sarna, Depts. of Surg. and Physiol., Medical College of Wisconsin and Zablocki VAMC, Milwaukee, WI. M 2 muscarinic receptors are coupled to Gt protein whose activation decreases adenylate cyclase activity. The aim of this study was to determine whether this signaling pathway is modulated by inflammation in the ileal longitudinal and circular muscle ceils. Circular but not longitudinal muscle contractility is depressed during acetic acid-induced ileal inflammation. Methods: Dog ileal longitudinal and circular muscle strips (2 x 2 mm) were incubated in 100 ~M IBMX for 20 min at 37" C. Forskolin (10 laM) was used to activate adenylate cyclase for 10 min. The decrease of adenylate cyclase activity by M2 receptor activation was determined by incubating the muscle strips with 10 laM methacholine for 1 min prior to their incubation with forskolin. Reactions were terminated by adding 2 volumes of ice-cold 6% trichloroacetic acid. cAMP levels were determined by the competitive protein binding assay (Amersham). Ileal inflammation was induced by a series of three mucosal exposures to ethanol and acetic acid. Results: The basal cAMP levels were not different between the normal longitudinal and circular muscle tissue (338 - 80 vs 278 -+ 75 pmol / mg protein, n = 4 resp.). Ileal inflammation did not alter the basic cAMP levels in the two muscle layers (321 + 55 and 301-+ 55 pmol / mg protein resp). Forskolin (10 ~aM) increased cAMP production 5.3 - 0.5 and 5.2 +- 1.1-fold over basal levels in the two muscle Iayers. This increase was not significantly different from that induced in the inflamed tissue, 6.9 +--1.0 and 6.9 _+1.6-fold respectively. Methacholine (10 laM) decreased cAMP production by 54-+ 5% in normal longitudinal muscle (p < .05) but by only 6.6 ± 8.3% (p > .05) in normal circular muscle.
Ileal inflammation did not affect the cAMP decrease bY methacholine in the longitudinal muscle (50 -+ 6%, p > .05, n = 4) but it significantly enhanced the cAMP decrease in the circular muscle (34 +-5%, p <.05, n = 4) Conclusions: In normal ileum, muscarinic receptor activation is coupled to adenylate cyclase in the longitudinal but not in the circular muscle. Inflammation does not alter this coupling in the longitudinal muscle but establishes it in the circular muscle. However, inflammation does not alter the basal levels of adenylate cyclase in the longitudinal or the circular muscle. The newly developed coupling between M2 receptors and adenylate cyclase may enable the circular muscle cells to contract partially in the inflamed state. • G3436 REDUCED Ca 2+ INFLUX CONTRIBUTES TO DECREASED CONTRACTILITY OF CIRCULAR MUSCLE CELLS IN COLONIC INFLAMMATION. X-Z. Shi and S.K. Sama. Depts. of Surgery and Physiology. Medical College of WI and Zablocki VAMC, Milwaukee, WI. Ca2÷ influx is an important source of Ca2÷ for the contractility of several types of smooth muscle cells. We investigated whether Ca2+ influx plays a role in the contraction of dispersed canine colonic circular muscle cells. If so, does a reduction in Ca2+ influx contribute to the suppression of circular muscle contractions during colonic inflammation? Methods: Healthy relaxed circular muscle cells were dispersed enzymatically from normal and inflamed proximal canine colons. Inflammation was induced by mucosal exposure to 75 mL of 95% ethanol and 20 mL of 60% acetic acid. Cell contractions were measured as percent decrease in length by scanning micrometry. The change in cytosolic free Ca2+concentration in response to agonists was measured in cell suspensions using the fluorescent dye Fura-2AM. Results: The lengths of dispersed circular smooth muscle cells obtained from the normal and the inflamed colon were not different from each other (97.8 -+4.2 and 96.9 -+4.6 Jam, n = 6 and 5 resp., p > 0.05). The dose response curves to muscarinic receptor agonist ACh (10-12 to 10,6 M), membrane depolarizer KCI (25 to 100 mM), and Ca2+ channel opener BAY K 8644 (10 -n to 10-5 M), were significantly suppressed in the inflamed cells. The maximum cell length shortening decreased from 25.4- 2.3% to 14.6-+ 3.6% for ACh at 10-8 M (n = 6 and 5, p <0.05) 25.2-+3.8% to 10.4-+5.2% for KC1 at 50 mM (n= 4 and 4, p <.05) and from 28.4 + 3.3% to 14.0 -+4.7% to BAY K 8644 at 10-6 M (n = 4 and 3, p <0.05). L- type Ca2+channel blocker, D600 (10-12to 10-6 M) dose-dependently decreased the response to ACh in normal and inflamed cells. The residual responses at the maximum dose of D600 were 8 -+3.4 and 5.1 _+ 1.2% in normal and inflamed cells. The ACh-induced decrease in length was completely blocked in Ca2+-free EGTA solution in normal and inflamed cells. The increase in cytosolic free Ca2+ in response to 50 mM KC1 was smaller in inflamed cells than in normal cells (61.7 vs 88%, n = 2). Conclusions: Ca2+ influx is required for the contraction of canine colonic circular muscle cells. Most influx occurs through L-type Cae÷ channels. Inflammation reduces the contractility of colonic circular smooth muscle cells. This may in part be due to a decrease in Ca2+ influx. • G3437 THE HERBAL MEDICINE, DAI-KENCHU-TO, STIMULATES UPPER GI MOTILITY IN CONSCIOUS DOGS VIA CHOLINERGIC AND 5-I-IT3 RECEPTORS. C. Shibata, I. Sasaki, H. Naito, N. Ohtani, T. Ueno, Y. Funayama, K. Fukushima, S. Matsuno. First Dept. of Surgery, Tohoku University School of Medicine, Sendal 980-8574, JAPAN. Dai-Kenchu-To (DKT), a herbal medicine consisting of 50 % Dried Ginger Rhizome (DGR), 30 % Ginseng Root (GR), and 20 % Zanthoxylum Fruit (ZF), is effective for reversing postoperative intestinal obstruction when administered into the stomach, but its mechanism of action is unknown. AIMS: To investigate effects of intragastric DKT, DGR, GR, and ZF on upper GI motility and the mechanism of action of DKT. METHODS: Six mongrel dogs were equipped with four strain gauge force transducers on the gastric body, antrum, duodenum, and jejunum to measure contractile activity of the circular muscle. DKT (1.5 g), ZF (1.0 g), GR (1.0 g), or DGR (1.0 g) dissolved in 50 ml 0.9 % NaC1 were administered into the gastric body through a silicone tube. The motor response obtained with 50 ml saline was used as a control. Effects of intravenous administration of atropine (muscarinic antagonist, 0.1 mg/kg + 0.1 mg/kg-h), hexamethonium (nicotinic antagonist, 5 mg/kg + 10 mg/kg-h), phentolamine (a-blocker, 0.5 mg/kg + 0.5 mg/kg-h), propranolol (13-blocker, 0.5 mg/kg + 0.5 mg/kg-h), or ondansetron (5-HT 3 antagonist, 0.3 mg/kg) on intragastric DKT-induced contractions was studied. Area under the contractile curve for 30 minutes after administration was measured and expressed as motor index (MI). RESULTS: Intragastric DKT increased MI (mean +-SEM), compared to control, in the antrum (1.9 _+0.4 vs. 0.6 - 0.1, p<0.05), duodenum (2.5 -+ 0.4 vs. 0.9 +-0.2, p<0.05), and jejunum (2.8 -+0.6 vs. 1.0 +-.0.2, p<0.05) but not in the gastric body (0.9 +_.0.2 vs. 0.8-+ 0.2). Intragastric DGR increased MI only in the gastric antrum. Intragastric GR had no effect on upper GI motility, whereas intragastric ZF increased MI in the duodenum and jejunum. Intragastric DKT-induced contractions were inhibited by atropine and ondansetron at all sites. Hexamethonium inhibited DKT-induced contractions in the duodenum and jejunum. Phentolamine and propranolol did not affect intragastric DKT-induced contractions at any site. CONCLUSIONS: Intragastric DKT stimulates upper gastrointestinal motility through cholinergic and 5-HT3 receptors. The different herb components of DKT stimulate motility at different sites; DGR mainly stimulated antral motility, whereas ZF stimulated duodenal and jejunal motility.