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Mechanisms of rabbit esophageal mucosal resistance to acid injury
A260
AGA ABSTRACTS
• ASSOCIATION OF HELICOBACTER PYLORI (lip) INFECTION WITH HYPOALBUMINEMIA AND DIETARY HABITS. B.C.Y.Wone, C.K.Ching, S.K.Lam, K.C.Lai, W.H.C.Hu, L.Y~Ong, C.L.Lai, C.K.Chan. Dept. of Medicine, University of Hong Kong, Hong Koag. We have recently conducted a large scale epidemiolgy study to document the prevalence and risk factors for Hp infection among the healthy elderly. Previous studies were limited by the small sample size. Materials & methods Sera obtained from 1698 asymptomatic Chinese subjects (239 males, 987 females; mean age 70.6 yrs, range 56-95 yrs) were tested for anti-Hp IgG antibody by using the GAP IgG ELISA kits (Bio-Rad). Their liver function tests and lipid profiles were also examined. Dietary habits were evaluated by a standard questionnaire. Multivariate analysis was performed to test the correlation between Hp infection and these parameters (blood tests and dieiary habits). Results 1226/1698 subjects (72.2%) were positive for anti-Hp antibody. Overall, the males (78.1%) had a significantly higher Hp + rate than the females (70.9%) (P<0.01). There was no appreciable difference in the Hp+ rates for both sexes within each Centile between 56-95 years. Furthermore, there was no evidence of singificant increase in Hp carrier rates with advancing age among this population. Hypoalbuminemia ( < 40g/l) but not other biochemical parameters was associated with a higher Hp + rates (p < 0.05). There was no correlation between the lipid profiles (cholesterols & triglycerides) and Hp + rates. An inverse relationship between the frequency of nuts consumption and Hp + rates was observed (p < 0.01). Other dietary (consumption of fast food, sea food, preserved food etc.) and cooking habits (type of cooking oil, boiled, fried or grill etc.) had no influence on the Hp+ rates. ': Conclusions (1) The overall Hp + rate among the elderly Chinese in Hong Kong was approx. 70%; it reaches a plateau between the age of 56-65 yrs. (2) Men had significantly higher Hp carrier rates than women. (3)Hp+ rates did not increase with advancing age in the elderly between 56-95 yrs. (4) Hypoalbuminemia was associated with higher Hp+ rates which may reflect chronic underlying malnutrition. (5) Consuming nuts frequently may have a protective effect against Hp infection.
• IS EXERCISE-INDUCED ASTHMA (EIA) CAUSED BY GASTROESOPHAGEAL REFLUX (GER)? RA Wright, MA Sagatelian, ME Simons, SA MeClave, Dept Med, Univ of Louisville, Louisville, KY. INTRO: An acid-induced, vagaliy-mediated, ehoilnergie esophagobronchial reflex has been described whereby intraesophagcal acid perfusion causes bronchospasm. Reports of exertional gastroesophageal acid reflux prompted us to study the possibility that EIA could be related to GER. METHODS: Following an overnight fast, 10 athletes with a history of EIA (9M, 1F; mean age 31) were monitored by esophageal pH/motility (Microdigiteapper, Synectlcs, Ine, Arlington, TX), EKG, and art 02 sat (Nellcor, ]Me, Hayward, CA). After baseline monitoring at rest for 15 rain, subjects underwent rigorous treadmill exercise (80% of calculated maximal heart rate for sex and age) for 10 min, followed by continued monitoring for 30 min post-exercise. Spirometry (FEVI) was done prior to exercise, and repeated every 5 rain post-exercise for 30 rain. 2 subjects were retested at a later date following a test meal. EIA was defined by a decrease in FEV by 20% from baseline value, GER by intraesophageal pH < 4. RESULTS: All 10 subjects demonstrated a decrease in FEVt, in response to exercise, but only half (5/10) met the criteria for EIA. Although 60% (6/10) showed some evidence of GER (2 of which occurred immediately before or during exercise), only 3 subjects demonstrated a pathologic degree of reflux (pH < 4 for>4.2% of study period, DeMeester score>20). In 2 subjects retested postprandlally, ~FEV~ was no different in one and improved in the other despite increased GER in both. There was no significant correlation between GER and EIA (p=0.2). EIA was inversely related to amplitude of esophageal contractions (p=0.002) and directly related to % multipeaked contractions (p=0.08). No correlation was found between the duration or % normal peristaltic contractions and GER or EIA. CONCLUSIONS: EIA is not associated with exertlonal GER. The correlation between EIA and esophageal motor dysfunction raises the possibility of a common intrinsic smooth muscle abnormality, perhaps involving both the esophagus and the bronchus.
GASTROENTEROLOGY, Vol. 108, NO, 4
MECHANISMS OF RABBIT ESOPHAGEAL MUCOSAL RESISTANCE TO ACID INJURY. H. Wright, C.A. Kieffer, P.K. Din&a, G.P. Morris, W.G. Paterson. GI Diseases Research Unit, Queen's University, Kingston, Ontario, Canada. Our previous studies have suggested that mast cells (MC) and inflammatory mediators may play a role in acute acid injury in the opossum esophagus. Rabbit esophageal mucosa is known to be more resistant to acid injury, an effect that may be partly related to their somewhat thicker squamous epithelial layer. In order to determine whether differences in the release of inflammatory mediators may also contribute to this resistance, either 100 mM HCl or isoosmotie normal saline (NS) was perfused intraluminally in the rabbit mid-esophagus for 60 min, during which time effluent was collected via a catheter at the GE junction in 10 rain aliquots for the measurement of intraluminal clearance of histamine, and previously injected CrSl-EDTA (to measure epithelial permeability) and InLBSA (to measure voseular permeability). Histological damage scores were assessed by a blinded observer and MC staining performed to quantitate MC counts in the subepithelial layer. Unlike the opossum esophagus, 60 rain perfusion with 100 mM HC1 in the rabbit was not associated with significant histological damage when compared to NS perfused controls (damage score 0.8 + 0.3 in controls vs 1.24- 0.5 in HCl-perfused). In addition, 100 mM HCI perfusion did not cause epithelial or mierovascular permeability changes. MCs in the rabbit subepithelial layer were relatively sparse (!0 fold decrease i n counts compared to opossum) and were not different between the 100 mMHCI and NS perfused groups. Furthermore, unlike the opossum model, there was no significant increase in the luminal appearance of histamine following 100 mM HC1 perfusion. This study suggests that the relative resistance of the rabbit esophageal epithelium to HC1 may be partly due to the smaller population of subepithelial mast cells and decreased release of inflammatory mediators. (Supported by PSI Ontario)
• IMPAIRMENT OF ESOPHAGEAL LONGITUDINAL MUSCLE FUNCTION WITH. HIATUS HERNIA. S W u , S Lin, PJ Kahrilas. Department of Medicine, Northwestern University, Chicago, I l l i n o i s . . Esophageal peristalsis involves both sequential segmental shortening, attributable to longitudinal muscle, and circular muscle contraction. Each shortened esophageal segment is presumably lengthened by contraction of the subsequent segment. We hypothesized that hiatus hernia might impair this process because, ultimately, relengthening forces must stem from the tethering to the diaphragm. Methods: Seven normal volunteers and 11 patietits with endoscopically suspected hiatus hernia had metal clips endoscopically placed at the diaphragmatic hiatus, the squamocolumnar junction (SCJ), and =5 cm proximal to the SCJ (n=10). The SCJ was then imaged with videofluoroscopy during 10 ml barium swallows. Images (5Is) were digitized and analyzed using image analysis software to track the motion of the clips irelative to each other, to a fixed reference point on a vertebral body, and to the diaphragmatic hiatus. Maximal esophageal shortening and the maximal separation of the SCJ and hiatus were measured when the sCJ reached an apogee relative to its resting position. Elongation rate was determined from the time of maximal shortening until resting length was reestablished. Maximal distal esophageal shortening was determined comparing the minimal and maximal lengths ,of the esophageal segment defined by the clips. Results: Subjects were divided into three groups depending upon the proximity of the SCJ to the diaphragmatic hiatus at rest: Gpl,<0cm, n=7; Gp 2, 0-2cm, n=6; Gp 3, >2 era, n=5. Maximal shortening occurred 3-4 s after the pharyngeal swallow making it necessarily attributable to longitudinal muscle contraction. All aspects of longitudinal muscle activit~¢were impaired with pro$ressive Maximum Max SCJ to i Max distal esoph Elongation shortening (rmn) hiatus (mm) shortening (%) rate (mm/s) Gp 1 19.7+6 18.6+5 49-£--12(n=5) 4.2-&0.1 Gp 2 14.2.+.3" 21.6-Z-_8 " 31+8 (n=3)* 3.1-£-0.1" Gp 3 10.4+4" 45.6+12" 31+3 (n=2)* 1.7+1.3" *p<0.05 compared with Gp i, all values mean + SD degree of hiatus hernia (Table). Conclusions: 1) Longitudinal muscle contraction, .reflected by esophageal shortening during peristalsis, is progressively reduced with increasing degree of hiatus hernia, 2) Similarly, relengthening o f the esophagus occurs progressively more slowly with hiatus hernia suggesting a loss Of "recoil" by the phren0esophageal membrane tethering the esophagus to the diaphragm, 3) At least some of the esophageal shortening observed with hiatus hernia is attributable to chronically contracted or shortened, unapposed longitudinal muscle.
AGA ABSTRACTS
• ASSOCIATION OF HELICOBACTER PYLORI (lip) INFECTION WITH HYPOALBUMINEMIA AND DIETARY HABITS. B.C.Y.Wone, C.K.Ching, S.K.Lam, K.C.Lai, W.H.C.Hu, L.Y~Ong, C.L.Lai, C.K.Chan. Dept. of Medicine, University of Hong Kong, Hong Koag. We have recently conducted a large scale epidemiolgy study to document the prevalence and risk factors for Hp infection among the healthy elderly. Previous studies were limited by the small sample size. Materials & methods Sera obtained from 1698 asymptomatic Chinese subjects (239 males, 987 females; mean age 70.6 yrs, range 56-95 yrs) were tested for anti-Hp IgG antibody by using the GAP IgG ELISA kits (Bio-Rad). Their liver function tests and lipid profiles were also examined. Dietary habits were evaluated by a standard questionnaire. Multivariate analysis was performed to test the correlation between Hp infection and these parameters (blood tests and dieiary habits). Results 1226/1698 subjects (72.2%) were positive for anti-Hp antibody. Overall, the males (78.1%) had a significantly higher Hp + rate than the females (70.9%) (P<0.01). There was no appreciable difference in the Hp+ rates for both sexes within each Centile between 56-95 years. Furthermore, there was no evidence of singificant increase in Hp carrier rates with advancing age among this population. Hypoalbuminemia ( < 40g/l) but not other biochemical parameters was associated with a higher Hp + rates (p < 0.05). There was no correlation between the lipid profiles (cholesterols & triglycerides) and Hp + rates. An inverse relationship between the frequency of nuts consumption and Hp + rates was observed (p < 0.01). Other dietary (consumption of fast food, sea food, preserved food etc.) and cooking habits (type of cooking oil, boiled, fried or grill etc.) had no influence on the Hp+ rates. ': Conclusions (1) The overall Hp + rate among the elderly Chinese in Hong Kong was approx. 70%; it reaches a plateau between the age of 56-65 yrs. (2) Men had significantly higher Hp carrier rates than women. (3)Hp+ rates did not increase with advancing age in the elderly between 56-95 yrs. (4) Hypoalbuminemia was associated with higher Hp+ rates which may reflect chronic underlying malnutrition. (5) Consuming nuts frequently may have a protective effect against Hp infection.
• IS EXERCISE-INDUCED ASTHMA (EIA) CAUSED BY GASTROESOPHAGEAL REFLUX (GER)? RA Wright, MA Sagatelian, ME Simons, SA MeClave, Dept Med, Univ of Louisville, Louisville, KY. INTRO: An acid-induced, vagaliy-mediated, ehoilnergie esophagobronchial reflex has been described whereby intraesophagcal acid perfusion causes bronchospasm. Reports of exertional gastroesophageal acid reflux prompted us to study the possibility that EIA could be related to GER. METHODS: Following an overnight fast, 10 athletes with a history of EIA (9M, 1F; mean age 31) were monitored by esophageal pH/motility (Microdigiteapper, Synectlcs, Ine, Arlington, TX), EKG, and art 02 sat (Nellcor, ]Me, Hayward, CA). After baseline monitoring at rest for 15 rain, subjects underwent rigorous treadmill exercise (80% of calculated maximal heart rate for sex and age) for 10 min, followed by continued monitoring for 30 min post-exercise. Spirometry (FEVI) was done prior to exercise, and repeated every 5 rain post-exercise for 30 rain. 2 subjects were retested at a later date following a test meal. EIA was defined by a decrease in FEV by 20% from baseline value, GER by intraesophageal pH < 4. RESULTS: All 10 subjects demonstrated a decrease in FEVt, in response to exercise, but only half (5/10) met the criteria for EIA. Although 60% (6/10) showed some evidence of GER (2 of which occurred immediately before or during exercise), only 3 subjects demonstrated a pathologic degree of reflux (pH < 4 for>4.2% of study period, DeMeester score>20). In 2 subjects retested postprandlally, ~FEV~ was no different in one and improved in the other despite increased GER in both. There was no significant correlation between GER and EIA (p=0.2). EIA was inversely related to amplitude of esophageal contractions (p=0.002) and directly related to % multipeaked contractions (p=0.08). No correlation was found between the duration or % normal peristaltic contractions and GER or EIA. CONCLUSIONS: EIA is not associated with exertlonal GER. The correlation between EIA and esophageal motor dysfunction raises the possibility of a common intrinsic smooth muscle abnormality, perhaps involving both the esophagus and the bronchus.
GASTROENTEROLOGY, Vol. 108, NO, 4
MECHANISMS OF RABBIT ESOPHAGEAL MUCOSAL RESISTANCE TO ACID INJURY. H. Wright, C.A. Kieffer, P.K. Din&a, G.P. Morris, W.G. Paterson. GI Diseases Research Unit, Queen's University, Kingston, Ontario, Canada. Our previous studies have suggested that mast cells (MC) and inflammatory mediators may play a role in acute acid injury in the opossum esophagus. Rabbit esophageal mucosa is known to be more resistant to acid injury, an effect that may be partly related to their somewhat thicker squamous epithelial layer. In order to determine whether differences in the release of inflammatory mediators may also contribute to this resistance, either 100 mM HCl or isoosmotie normal saline (NS) was perfused intraluminally in the rabbit mid-esophagus for 60 min, during which time effluent was collected via a catheter at the GE junction in 10 rain aliquots for the measurement of intraluminal clearance of histamine, and previously injected CrSl-EDTA (to measure epithelial permeability) and InLBSA (to measure voseular permeability). Histological damage scores were assessed by a blinded observer and MC staining performed to quantitate MC counts in the subepithelial layer. Unlike the opossum esophagus, 60 rain perfusion with 100 mM HC1 in the rabbit was not associated with significant histological damage when compared to NS perfused controls (damage score 0.8 + 0.3 in controls vs 1.24- 0.5 in HCl-perfused). In addition, 100 mM HCI perfusion did not cause epithelial or mierovascular permeability changes. MCs in the rabbit subepithelial layer were relatively sparse (!0 fold decrease i n counts compared to opossum) and were not different between the 100 mMHCI and NS perfused groups. Furthermore, unlike the opossum model, there was no significant increase in the luminal appearance of histamine following 100 mM HC1 perfusion. This study suggests that the relative resistance of the rabbit esophageal epithelium to HC1 may be partly due to the smaller population of subepithelial mast cells and decreased release of inflammatory mediators. (Supported by PSI Ontario)
• IMPAIRMENT OF ESOPHAGEAL LONGITUDINAL MUSCLE FUNCTION WITH. HIATUS HERNIA. S W u , S Lin, PJ Kahrilas. Department of Medicine, Northwestern University, Chicago, I l l i n o i s . . Esophageal peristalsis involves both sequential segmental shortening, attributable to longitudinal muscle, and circular muscle contraction. Each shortened esophageal segment is presumably lengthened by contraction of the subsequent segment. We hypothesized that hiatus hernia might impair this process because, ultimately, relengthening forces must stem from the tethering to the diaphragm. Methods: Seven normal volunteers and 11 patietits with endoscopically suspected hiatus hernia had metal clips endoscopically placed at the diaphragmatic hiatus, the squamocolumnar junction (SCJ), and =5 cm proximal to the SCJ (n=10). The SCJ was then imaged with videofluoroscopy during 10 ml barium swallows. Images (5Is) were digitized and analyzed using image analysis software to track the motion of the clips irelative to each other, to a fixed reference point on a vertebral body, and to the diaphragmatic hiatus. Maximal esophageal shortening and the maximal separation of the SCJ and hiatus were measured when the sCJ reached an apogee relative to its resting position. Elongation rate was determined from the time of maximal shortening until resting length was reestablished. Maximal distal esophageal shortening was determined comparing the minimal and maximal lengths ,of the esophageal segment defined by the clips. Results: Subjects were divided into three groups depending upon the proximity of the SCJ to the diaphragmatic hiatus at rest: Gpl,<0cm, n=7; Gp 2, 0-2cm, n=6; Gp 3, >2 era, n=5. Maximal shortening occurred 3-4 s after the pharyngeal swallow making it necessarily attributable to longitudinal muscle contraction. All aspects of longitudinal muscle activit~¢were impaired with pro$ressive Maximum Max SCJ to i Max distal esoph Elongation shortening (rmn) hiatus (mm) shortening (%) rate (mm/s) Gp 1 19.7+6 18.6+5 49-£--12(n=5) 4.2-&0.1 Gp 2 14.2.+.3" 21.6-Z-_8 " 31+8 (n=3)* 3.1-£-0.1" Gp 3 10.4+4" 45.6+12" 31+3 (n=2)* 1.7+1.3" *p<0.05 compared with Gp i, all values mean + SD degree of hiatus hernia (Table). Conclusions: 1) Longitudinal muscle contraction, .reflected by esophageal shortening during peristalsis, is progressively reduced with increasing degree of hiatus hernia, 2) Similarly, relengthening o f the esophagus occurs progressively more slowly with hiatus hernia suggesting a loss Of "recoil" by the phren0esophageal membrane tethering the esophagus to the diaphragm, 3) At least some of the esophageal shortening observed with hiatus hernia is attributable to chronically contracted or shortened, unapposed longitudinal muscle.