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Pressure at the gastroesophageal junction increases in man during gastric air distension
April 2000
AGAA155
position. Studies were performed before, immediately, 10 and 20 wks after balloon placement. Results: The residual LES pressure after water swallows (5ml) was not affected after balloon placement, excluding mechanical interaction with sleeve function. Basal LES pressure was significantly increased after 10 (24 (l4-34)mmHg) and 20 wks (26 (l5-36)mmHg) compared to before (16 (l1-22)mmHg). Immediately after introduction of the balloon, the rate of TLESRs was significantly increased (10 (6-14 jn.h I). After 10 (5 (2-7)n.h,l)and 20 wks (3 (2-3)n.h,l)the rate of TLESRs returned to baseline values (4 (2-6)n.h· I ) . The percentage of TLESRs accompanied by a reflux episode was significantly increased in the supine position after 10 and 20 wks (85 (69-100)% vs before: 32 (16-49)%), but not in the sitting position. In addition, the rate of reflux episodes was increased after 10 and 20 wks (4 (3-6)n.h·] vs before: 1(0-2)n.h·') with an increase in the %time pH<4 after 10 wks (8 (5-11)% vs before: 4 (-2-9)%). TLESR were the main mechanism underlying reflux (58-78%). In addition we observed gastric contractions which were associated with reflux in 2-25% of the cases. Summary & Conclusion: We showed that an intragastric balloon only initially increases TLESRs, but not after 10 and 20 wks,. This illustrates adaptation in time of the reflex pathway underlying TLESRs. Nevertheless, gastroesophageal reflux was significantly increased after balloon placement in the supine position, due to an increased percentage of reflux during TLESRs. The mechanism underlying this remains to be elucidated.
891 PRESSURE AT THE GASTROESOPHAGEAL JUNCTION IN· CREASES IN MAN DURING GASTRIC AIR DISTENSION. Benson T. Massey, Subashini Narayanan. Ronald C. Arndorfer, Med Coli of Wisconsin, Milwaukee, WI. BACKGROUND: Basal pressure at the gastroesophageal junction (GElP) results from the action of both the lower esophageal sphincter (LES) and the diaphragmatic crura. Controversy exists as to whether gastric distension causes no change or even a decrease in GEJP. METHODS: 12 healthy volunteers (8M/4F, age 22-50 yrs) were studied while fasting and seated. Pharyngeal, esophageal body, GEl, and gastric pressures were continuously recorded with perfused manometry catheters, which included a sleeve device at the GEl. Recordings were performed at baseline and during barostatically controlled gastric distensions with unconstrained air at target pressures of 10.0,12.5,15.0, and 17.5 mmHg. Distensions were performed at each pressure for 30 minutes in random order. At one minute intervals end-inspiratory (Insp) and end-expiratory (Exp) GEJPs were recorded from the sleeve channel and concurrent gastric pressures were also recorded. Care was taken to avoid taking measurements during deglutitive or transient LES relaxations. ANOVA and paired t-tests were used to compare differences between GEJPs during different conditions both with (net)and without (absolute)reference to gastric pressure. RESULTS: Both absolute inspiratory and expiratory GEJPs increased during gastric distension, as shown in the table. These increases were mostly, but not completely, negated when adjusted for the increases in gastric pressure during distension. CONCLUSIONS: Contrary to some earlier reports, during gastric distension with air the absolute GEJP increases to offset the increase in gastric pressure. This response likely serves to maintain a pressure differential that decreases the possibility of spontaneous reflux across the GEJ, similar to what occurs with straining. Supported in part by POI DC03191-01. DistPress Absolute Exp GEJP Absolute InspGEJP NetExp GEJP NetInspGEJP
OmmHg 26±3 41±4 16±3 31±3
Data expressed as mean±SEM;
10mmHg 34±4 50±5 20±4 36±5
* * * *
12.5mmHg 35±4 50±4 19±3 35±4
* * * *
15.0 mmHg
17.5 mmHg
34±4 * 49±4 * 17±3 32±4
36±4 * 50±5 * 19±4 32+5
* = sign. higher than with nodistension
892 GENERATION OF NO IN THE OPOSSUM LES DURING PHYSI· OLOGICAL EXPERIMENTATION. Hyojin Park, Eugene Clark, Jeffrey 1. Conklin, Yonsei Univ Coli of Medicine, Seoul, South Korea; Iowa City VA Med Ctr, Iowa City, IA; Univ of Iowa Coli of Medicine and VA Med Ctr, Iowa City, IA. Lipopolysaccharide (LPS) given in vivo modulates opossum esophageal motor functions by inducing the inducible NO synthase (iNOS)which increases nitric oxide (NO) production. The NO scavenger superoxide (O;)is also generated during endotoxemia. It is cleared by superoxide dismutase (SOD) and catalase (Cat)to protect the physiological function of NO. We studied whether LES motility, NO release and iNOS expression in the lower esophageal sphincter (LES) are affected by LPS in vitro. Muscle strips from the opossum LES were placed in tissue baths containing oxygenated Krebs Ringer buffer, NO release was measured with a chemiluminescence NOx analyzer, and western blots were done for iNOS expression. Resting LES tone increased during LPS exposure. The LPSinduced increase in tone was antagonized by SOD/Cat. The % change in NO concentration in the tissue bath of LPS treated muscle not undergoing nerve stimulation was significantly less than control, but was increased in the LPS group when treated with SOD/Cat.After 6 hrs exposure to LPS, the EFS-induced release of NO was, however, decreased as compared to
pretreatment. The % LES relaxation was decreased in the control group at 6 hrs. The expression of iNOS was increased in LES muscle of the control and LPS treated group. These studies suggest that NO production is increased in control and LPS treated tissues in vitro, and that LPS also increases 0; production in vitro. Superoxide and antioxidant enzymes may playa role in regulating NO-mediated neuromuscular functions of the LES.
893 IS TRANSIENT LOWER ESOPHAGEAL SPHINCTER RELAX· AT10N TRIGGERED BY PHASIC CONTRACTIONS OR TONIC CHANGES OF THE PROXIMAL STOMACH? Mariangela Allocca, Paolo A. Bianchi. Roberto Penagini, Hosp Maggiore, Milan. Italy. Triggering of transient lower esophageal sphincter relaxation (TLESR)is still obscure. Continuous distension of the proximal stomach is a potent stimulus. However, as TLESR is a discrete event, it could be hypothesized that it is triggered by a discrete motor event, i.e. a phasic contraction or a tonic change in the proximal stomach, whereas distension exerts only a permissive role. Methods: in order to test this hypothesis we reviewed the combined esophageal manometry-gastric barostat tracings of the 10 minutes before all TLESRs not preceded by another TLESR within this time frame (n=52). Tracings were obtained from II healthy subjects, aged 23-32 yr, 3 men, during a 2h isobaric gastric distension experiment at an intrabag pressure of II ± I mmHg. Volume waves, i.e. phasic contractions (Gastroenterology 1987;92:934-943), were analyzed in the minute before onset of each TLESR (pre-TLESR period) and in a preceding minute (control period). Similarly, intrabag volume. i.e. proximal gastric tone, was measured in the 5 minutes before onset of each TLESR and in the preceding 5 minutes. Results (mean±SEM): as shown in the table below, number. amplitude and duration of volume waves. and intrabag volumes were similar in the pre-TLESR and control period. Conclusions: our observations suggest that TLESR is not triggered by a preceding phasic contraction or tonic change of the proximal stomach. The mechanism of triggering of TLESRs remains to be elucidated.
volume waves: number amplitude (ml) duration (sec) interval (sec) t 5 min.intrabag volume(ml)
pre·TLESR period
control period
O,6±O,1 86±8 31±3 33±3 529±77
O,5±O,1 89±8 38±4 532±74
t before onset ofTLESR
894 GANGLIONIC AND NEUROEFFECTOR TRANSMISSION TO THE FERRET LOWER ESOPHAGEAL SPHINCTER IN A NOVEL IN VITRO OESOPHAGOGASTRIC PREPARATION. Scott Darryl Srnid, 1. Ashley Blackshaw. Royal Adelaide Hosp, Adelaide, SA. Australia. The lower esophageal sphincter (LES) receives autonomic innervation primarily through the vagus nerve, which synapses with enteric inhibitory and excitatory motorneurons in the myenteric plexus to alter LES tone. In the present study we aimed to discretely characterize ganglionic and neuroeffector transmission to the LES in a novel in vitro esophagogastric preparation, with intact vagal innervation. Circular muscle rings of LES. with attached vagus nerves, were prepared from adult ferrets and maintained in organ baths. where tension of LES muscle was measured. LES responses to vagal stimulation (0.5-5 Hz. 30V) were recorded, alone and following pretreatment with tetrodotoxin (TTX), hexamethonium (Hex), Hex and atropine and NG-nitro-L-arginine (L-NNA). Direct activation of enteric inhibitory motorneurons was performed by addition of KCI (20 mM). Vagal stimulation elicited frequency-dependent relaxations of the LES that were abolished by tetrodotoxin (I /LM) and markedly reduced following L-NNA pretreatment (100 /LM). Hex alone (500 /LM) reduced maximal relaxation by 40%; in combination with atropine (2 /LM). relaxation was almost abolished. Direct activation of enteric motorneurons with KCI (20 mM) evoked LES relaxation; this was unaltered by L-NNA, Hex or Hex+atropine pretreatment. but was reversed to a contraction in the presence of TTX. These results show that neurotransmission from vagal preganglionic neurons to the myenteric plexus in ferret LES occurs mainly via a combination of nicotinic and muscarinic receptors and utilizes nitric oxide as the final common mediator from enteric motorneurons. By contrast. LES relaxation by KCI. while neurogenic in origin, probably involves additional release of neurotransmitters other than NO from inhibitory motorneurons that are not coupled to vagal preganglionic neurons. Supported by AstraZeneca.
AGAA155
position. Studies were performed before, immediately, 10 and 20 wks after balloon placement. Results: The residual LES pressure after water swallows (5ml) was not affected after balloon placement, excluding mechanical interaction with sleeve function. Basal LES pressure was significantly increased after 10 (24 (l4-34)mmHg) and 20 wks (26 (l5-36)mmHg) compared to before (16 (l1-22)mmHg). Immediately after introduction of the balloon, the rate of TLESRs was significantly increased (10 (6-14 jn.h I). After 10 (5 (2-7)n.h,l)and 20 wks (3 (2-3)n.h,l)the rate of TLESRs returned to baseline values (4 (2-6)n.h· I ) . The percentage of TLESRs accompanied by a reflux episode was significantly increased in the supine position after 10 and 20 wks (85 (69-100)% vs before: 32 (16-49)%), but not in the sitting position. In addition, the rate of reflux episodes was increased after 10 and 20 wks (4 (3-6)n.h·] vs before: 1(0-2)n.h·') with an increase in the %time pH<4 after 10 wks (8 (5-11)% vs before: 4 (-2-9)%). TLESR were the main mechanism underlying reflux (58-78%). In addition we observed gastric contractions which were associated with reflux in 2-25% of the cases. Summary & Conclusion: We showed that an intragastric balloon only initially increases TLESRs, but not after 10 and 20 wks,. This illustrates adaptation in time of the reflex pathway underlying TLESRs. Nevertheless, gastroesophageal reflux was significantly increased after balloon placement in the supine position, due to an increased percentage of reflux during TLESRs. The mechanism underlying this remains to be elucidated.
891 PRESSURE AT THE GASTROESOPHAGEAL JUNCTION IN· CREASES IN MAN DURING GASTRIC AIR DISTENSION. Benson T. Massey, Subashini Narayanan. Ronald C. Arndorfer, Med Coli of Wisconsin, Milwaukee, WI. BACKGROUND: Basal pressure at the gastroesophageal junction (GElP) results from the action of both the lower esophageal sphincter (LES) and the diaphragmatic crura. Controversy exists as to whether gastric distension causes no change or even a decrease in GEJP. METHODS: 12 healthy volunteers (8M/4F, age 22-50 yrs) were studied while fasting and seated. Pharyngeal, esophageal body, GEl, and gastric pressures were continuously recorded with perfused manometry catheters, which included a sleeve device at the GEl. Recordings were performed at baseline and during barostatically controlled gastric distensions with unconstrained air at target pressures of 10.0,12.5,15.0, and 17.5 mmHg. Distensions were performed at each pressure for 30 minutes in random order. At one minute intervals end-inspiratory (Insp) and end-expiratory (Exp) GEJPs were recorded from the sleeve channel and concurrent gastric pressures were also recorded. Care was taken to avoid taking measurements during deglutitive or transient LES relaxations. ANOVA and paired t-tests were used to compare differences between GEJPs during different conditions both with (net)and without (absolute)reference to gastric pressure. RESULTS: Both absolute inspiratory and expiratory GEJPs increased during gastric distension, as shown in the table. These increases were mostly, but not completely, negated when adjusted for the increases in gastric pressure during distension. CONCLUSIONS: Contrary to some earlier reports, during gastric distension with air the absolute GEJP increases to offset the increase in gastric pressure. This response likely serves to maintain a pressure differential that decreases the possibility of spontaneous reflux across the GEJ, similar to what occurs with straining. Supported in part by POI DC03191-01. DistPress Absolute Exp GEJP Absolute InspGEJP NetExp GEJP NetInspGEJP
OmmHg 26±3 41±4 16±3 31±3
Data expressed as mean±SEM;
10mmHg 34±4 50±5 20±4 36±5
* * * *
12.5mmHg 35±4 50±4 19±3 35±4
* * * *
15.0 mmHg
17.5 mmHg
34±4 * 49±4 * 17±3 32±4
36±4 * 50±5 * 19±4 32+5
* = sign. higher than with nodistension
892 GENERATION OF NO IN THE OPOSSUM LES DURING PHYSI· OLOGICAL EXPERIMENTATION. Hyojin Park, Eugene Clark, Jeffrey 1. Conklin, Yonsei Univ Coli of Medicine, Seoul, South Korea; Iowa City VA Med Ctr, Iowa City, IA; Univ of Iowa Coli of Medicine and VA Med Ctr, Iowa City, IA. Lipopolysaccharide (LPS) given in vivo modulates opossum esophageal motor functions by inducing the inducible NO synthase (iNOS)which increases nitric oxide (NO) production. The NO scavenger superoxide (O;)is also generated during endotoxemia. It is cleared by superoxide dismutase (SOD) and catalase (Cat)to protect the physiological function of NO. We studied whether LES motility, NO release and iNOS expression in the lower esophageal sphincter (LES) are affected by LPS in vitro. Muscle strips from the opossum LES were placed in tissue baths containing oxygenated Krebs Ringer buffer, NO release was measured with a chemiluminescence NOx analyzer, and western blots were done for iNOS expression. Resting LES tone increased during LPS exposure. The LPSinduced increase in tone was antagonized by SOD/Cat. The % change in NO concentration in the tissue bath of LPS treated muscle not undergoing nerve stimulation was significantly less than control, but was increased in the LPS group when treated with SOD/Cat.After 6 hrs exposure to LPS, the EFS-induced release of NO was, however, decreased as compared to
pretreatment. The % LES relaxation was decreased in the control group at 6 hrs. The expression of iNOS was increased in LES muscle of the control and LPS treated group. These studies suggest that NO production is increased in control and LPS treated tissues in vitro, and that LPS also increases 0; production in vitro. Superoxide and antioxidant enzymes may playa role in regulating NO-mediated neuromuscular functions of the LES.
893 IS TRANSIENT LOWER ESOPHAGEAL SPHINCTER RELAX· AT10N TRIGGERED BY PHASIC CONTRACTIONS OR TONIC CHANGES OF THE PROXIMAL STOMACH? Mariangela Allocca, Paolo A. Bianchi. Roberto Penagini, Hosp Maggiore, Milan. Italy. Triggering of transient lower esophageal sphincter relaxation (TLESR)is still obscure. Continuous distension of the proximal stomach is a potent stimulus. However, as TLESR is a discrete event, it could be hypothesized that it is triggered by a discrete motor event, i.e. a phasic contraction or a tonic change in the proximal stomach, whereas distension exerts only a permissive role. Methods: in order to test this hypothesis we reviewed the combined esophageal manometry-gastric barostat tracings of the 10 minutes before all TLESRs not preceded by another TLESR within this time frame (n=52). Tracings were obtained from II healthy subjects, aged 23-32 yr, 3 men, during a 2h isobaric gastric distension experiment at an intrabag pressure of II ± I mmHg. Volume waves, i.e. phasic contractions (Gastroenterology 1987;92:934-943), were analyzed in the minute before onset of each TLESR (pre-TLESR period) and in a preceding minute (control period). Similarly, intrabag volume. i.e. proximal gastric tone, was measured in the 5 minutes before onset of each TLESR and in the preceding 5 minutes. Results (mean±SEM): as shown in the table below, number. amplitude and duration of volume waves. and intrabag volumes were similar in the pre-TLESR and control period. Conclusions: our observations suggest that TLESR is not triggered by a preceding phasic contraction or tonic change of the proximal stomach. The mechanism of triggering of TLESRs remains to be elucidated.
volume waves: number amplitude (ml) duration (sec) interval (sec) t 5 min.intrabag volume(ml)
pre·TLESR period
control period
O,6±O,1 86±8 31±3 33±3 529±77
O,5±O,1 89±8 38±4 532±74
t before onset ofTLESR
894 GANGLIONIC AND NEUROEFFECTOR TRANSMISSION TO THE FERRET LOWER ESOPHAGEAL SPHINCTER IN A NOVEL IN VITRO OESOPHAGOGASTRIC PREPARATION. Scott Darryl Srnid, 1. Ashley Blackshaw. Royal Adelaide Hosp, Adelaide, SA. Australia. The lower esophageal sphincter (LES) receives autonomic innervation primarily through the vagus nerve, which synapses with enteric inhibitory and excitatory motorneurons in the myenteric plexus to alter LES tone. In the present study we aimed to discretely characterize ganglionic and neuroeffector transmission to the LES in a novel in vitro esophagogastric preparation, with intact vagal innervation. Circular muscle rings of LES. with attached vagus nerves, were prepared from adult ferrets and maintained in organ baths. where tension of LES muscle was measured. LES responses to vagal stimulation (0.5-5 Hz. 30V) were recorded, alone and following pretreatment with tetrodotoxin (TTX), hexamethonium (Hex), Hex and atropine and NG-nitro-L-arginine (L-NNA). Direct activation of enteric inhibitory motorneurons was performed by addition of KCI (20 mM). Vagal stimulation elicited frequency-dependent relaxations of the LES that were abolished by tetrodotoxin (I /LM) and markedly reduced following L-NNA pretreatment (100 /LM). Hex alone (500 /LM) reduced maximal relaxation by 40%; in combination with atropine (2 /LM). relaxation was almost abolished. Direct activation of enteric motorneurons with KCI (20 mM) evoked LES relaxation; this was unaltered by L-NNA, Hex or Hex+atropine pretreatment. but was reversed to a contraction in the presence of TTX. These results show that neurotransmission from vagal preganglionic neurons to the myenteric plexus in ferret LES occurs mainly via a combination of nicotinic and muscarinic receptors and utilizes nitric oxide as the final common mediator from enteric motorneurons. By contrast. LES relaxation by KCI. while neurogenic in origin, probably involves additional release of neurotransmitters other than NO from inhibitory motorneurons that are not coupled to vagal preganglionic neurons. Supported by AstraZeneca.