Masahiko Tabata

Intestinal motility in an in vivo rat model of intestinal ischemia-reperfusion with special reference to the effects of nitric oxide on the motility changes.

Background To clarify the relation between intestinal ischemia–reperfusion (IR) and dysmotility, the authors investigated changes in the motility pattern in the duodenum and jejunum in an in vivo rat model of IR when artery- (and vein-) fed jejunum was clamped transiently. The authors also studied the effect of nitric oxide on the motility changes in this model by means of the administration of l -NAME (N G -nitro- l -arginine methyl ester) or S-methylisothiourea sulfate (SMT). Materials and Methods A force transducer was sutured onto the serosal side of the duodenum or jejunum. After a 3-to 4-day recovery period, contractions were recorded during periods of preischemia, ischemia (60 minutes), and reperfusion (90 minutes). An intestinal IR was produced by clamping and releasing the mesenteric artery and vein with artery forceps. Results In the jejunum, there was a prolongation in the duration of contraction and there were decreases in the number of contractions (NC) during the IR. When treated with L-NAME, no decrease in the NC was observed during the 45 to 90 minutes after reperfusion. S-methylisothiourea sulfate did not affect the IR-induced motility changes significantly. In the duodenum, there was a prolongation in the duration of contraction and a decrease in the NC and AC only during the reperfusion. l -NAME or S-methylisothiourea sulfate inhibited the decreases in the NC during the reperfusion. Conclusions Intestinal IR causes motility changes in the ischemic site during the IR and in the nonischemic site during the reperfusion. The IR-induced motility changes partly depend on nitric oxide production.

Y-27632 inhibits gastric motility in conscious rats

Y-27632, a highly selective inhibitor of p160ROCK, desensitizes the smooth muscle to Ca2+ and inhibits smooth muscle contraction. While this drug has the potential to become a novel drug for hypertension, it might also affect other smooth muscle, including that of gastrointestinal tract. We studied the effects of Y-27632 on gastric contractions in conscious rats. Strain gauge force transducers were sutured onto the serosal side of the gastric antrum and contractions were recorded before and after the intravenous injection of Y-27632. Doses of 1.0 mg/kg to 10 mg/kg significantly decreased contraction amplitude and the motility index in a dose dependent manner. With 10 mg/kg, the mean amplitude was decreased by up to 69 +/- 14% and the motility index by up to 81 +/- 7%. The change occurred immediately after drug infusion and lasted for 3.5h. Contraction frequency showed only a slight decrease. No signs of bowel obstruction were observed. These results indicate that Rho-mediated Ca sensitization has a role in the physiologic contractions of gastric smooth muscle in rats. Y-27632 is useful to investigate the physiology of gastrointestinal motility.

Analysis of Gastrointestinal Sounds in Infants With Pyloric Stenosis Before and After Pyloromyotomy

Background. Although recent advances in computer technology enable us to analyze gastrointestinal sounds data objectively with ease, this clinical application has been investigated in only a few disorders. To investigate one potential role of this approach in pediatric practice, we recorded and analyzed gastrointestinal sounds in infants with hypertrophic pyloric stenosis (HPS), a motility-related disorder that is common in children. Methods. In 15 infants with pyloric stenosis, gastrointestinal sounds were collected with a microphone placed 3 cm below the umbilicus for 60 minutes before pyloromyotomy and at 9 to 12 hours, 20 to 24 hours, 40 to 48 hours, and 112 to 120 hours after the operation. Data were entered into a computer to sum the amplitude of sound signals as a sound index (SI; mV per minute). In 12 infants, gastric emptying was measured immediately before each sound recording, using a marker dilution-double sampling method. Results. Before surgery, the mean SI was 4.6 ± 1.0 mV per minute, significantly less than in healthy controls (31.7 ± 8.4 mV per minute). The SI remained in a similar range until 12 hours after operation, after which it began increasing to reach the normal range by 48 hours after operation (30.0 ± 9.4 mV per minute). Gastric emptying, also low in HPS before pyloromyotomy, increased by 4 to 5 times after surgery. There was a significant positive correlation between SI and gastric emptying. The incidence of postoperative symptoms (such as vomiting) were correlated significantly with SI at 24 hours after surgery. Conclusion. This study found decreased gastrointestinal sounds to be among physical findings suggestive of HPS and a useful indicator of gastric emptying and bowel motility after pyloromyotomy. Computer-assisted analysis of gastrointestinal sounds might be helpful in clinical practice for pediatric patients with some gastrointestinal disorders.

Ultrasonographic assessment of intragastric volume in neonates: Factors affecting the relationship between intragastric volume and antral cross-sectional area

Measuring antral crosssectional area by ultrasonography can be an ideal way to evaluate intragastric milk volume in infants. Technical details, however, remain to be established before its clinical application. We investigated the effects of posture and ultrasonographic plane on the correlation between milk volume and antral cross-sectional area. After gastric aspiration through a nasogastric tube, healthy newborns were fed 0, 10, 20, and 40 ml of milk cumulatively, and antral cross-sectional area was measured in either upright, sitting, or right lateral position. To determine the best sonographic plane, subjects were put in the right lateral position and antral cross-sectional area was measured in the plane of the aorta and either the superior mesenteric artery, the superior mesenteric vein, the midline of the abdominal surface, 1 cm right of midline, or 2 cm right of midline. The results showed that antral cross-sectional area reflects intragastric milk volume most accurately, with minimal gas interference when measured in the right lateral position. The area correlates well with milk volume in the plane of the aorta and either the superior mesenteric artery, the superior mesenteric vein, or the midline. Next, we studied the effect of intragastric gas on the antral cross-sectional area in subjects who were given 40 ml of milk followed by an injection of air. More than 20 ml of intragastric gas increases antral cross-sectional area significantly. Ultrasonographic evaluation of intragastric volume requires attention to the above factors.

Effect of 10% Ethanol and Sofalcone on Prostaglandin E2 Content, Mucus Gel Thickness, and Experimental Ulcers in the Stomach of Developing Rats

We studied the effects of a mild irritant, 10% ethanol, and sofalcone on the gastric mucosal defense mechanisms in newborn rats, comparing the effects to those seen in adult rats. The results indicated (1) that both mucosal prostaglandin E2 (PGE2) content and mucus gel layer thickness increased with age, (2) that sofalcone, but not 10% ethanol, increased mucosal PGE2 content and mucus gel thickness in 1- and 8-week-old rats, (3) that both sofalcone and 10% ethanol decreased mucosal damage induced by 50 or 75% ethanol in both age groups, and (4) that 10% ethanol, but not sofalcone, decreased ethanol-induced mucosal damage in rats pretreated with indomethacin. We concluded that 10% ethanol and sofalcone increase gastric mucosal defence mechanisms in newborn rats as in older rats.

Developmental changes in gastric mucus gel thickness: responsiveness to 16,16-dimethyl prostaglandin E2 and mucosal protection in the rat.

The gastric mucosa of newborn rats is sensitive to the damaging effects of acid and ethanol. We measured gastric mucus gel thickness in newborn, suckling, and weaned rats by inversion microscopic observation. The thickness in newborn rats was 52.2 ± 6.7 Mm and increased with age, reaching 96.8 ± 5.6 μm in 8-wk-old rats (p < 0.001). Oral administration of 16, 16-dimethyI prostaglandin E2 at concentrations of 10 and 100 μg/kg body weight increased mucus thickness in 8-wk-old rats but had no effect in 1-wk-old rats. We also assessed the effect of 16, 16-dimethyl prostaglandin E2 on the prevention of gastric mucosal damage induced by ethanol. Oral 16, 16-dimethyl prostaglandin E2 reduced damage in 8-wk-old rats, but there was no effect in 1-wk-old rats. These data suggest that the susceptibility of newborn rats to gastric mucosal injury may be related to the relative thinness of the gastric mucus gel layer and the failure of prostaglandins to increase the mucus gel layer thickness.

Developmental changes in cyclooxygenase mRNA expression in the gastric mucosa of rats.

Background In newborn rats, gastric mucosa is more susceptible to various damaging agents and recovers from injury more quickly than in older animals. To determine whether metabolism of prostaglandins is responsible for this mucosal protective mechanism in developing rats, we studied cyclooxygenase (COX) mRNA expression in the mucosa using quantitative real-time polymerase chain reaction (PRC). Methods Cyclooxygenase-1 and COX-2 mRNA was extracted from the gastric mucosa of rats of various ages and quantitatively analyzed using real-time PCR with dual-labeled fluorogenic probes. The copy numbers of cDNA for COX-1 and COX-2 were standardized to glyceraldehyde-3-phosphate dehydrogenase from the same sample. Results Cyclooxygenase-1 mRNA expression was lowest in 1-week-old rats and highest in 4-week-old rats. Mucosal damage produced by 150 mmol/L HCl and 60% ethyl alcohol did not increase COX-1 mRNA expression in any age group. Cyclooxygenase-2 mRNA expression increased significantly with age. Mucosal injury increased COX-2 mRNA in each age group, especially in 1-week-old rats. Intraperitoneal lipopolysaccharide also increased COX-2 mRNA in both 1- and 4-week old rats. Conclusion The high level of COX-2 mRNA expression in the gastric mucosa of 1-week-old rats may be responsible for the physiologic characteristics of gastric mucosal defenses in this age group.

Involvement of Serotonin and Nitric Oxide in Endotoxin-Induced Gastric Motility Changes in Conscious Rats

Severe bacterial infection causes gastrointestinal dysmotility by an unknown mechanism. We investigated the possible involvement of serotonin (5-HT) and nitric oxide (NO) in endotoxin-induced motility disturbance, using an in vivo rat model. Six days prior to the experiment, a force transducer was sutured to the gastric antrum of rats. Lipopolysaccharide induced strong repetitive contractions in the gastric antrum within 2 to 3 min in all rats tested. After 15 min of hypermotility, motility decreased and remained low for more than 60 min. The initial increase in motility was suppressed by atropine, FK1052, or SB204070, whereas it was not affected by granisetron. The subsequent decrease was inhibited by l-NAME and S-methylisothiourea sulfate. These results indicate that in conscious rats, lipopolysaccharide induces a transient increase in gastric motility followed by suppression. The increase might be mediated by 5-HT4 receptors, and the decrease by inducible NOS.

Gastrointestinal manometry findings in a case with dilated small bowel and disturbed transit treated successfully with bowel plication

Abstract We report the manometric findings in a case of dilated small bowel and disturbed transit successfully treated with plication of the dilated small bowel. The female newborn infant required total parenteral nutrition following an operation for small bowel atresia. X‐ray showed a dilated proximal small bowel. Jejunal manometry showed normal phase 3 migration but persistently low‐amplitude contractions in the dilated segment. After plication of the dilated intestine, symptoms of bowel obstruction disappeared. A second manometry two weeks after the operation showed contractions with normal amplitude. These findings indicate that: (1) disturbed transit in the dilated intestine proximal to small intestinal atresia is associated with persistently low contraction amplitude, and (2) the amplitude can be increased by the plication of the dilated loop.

Maturational Changes in Airway Remodeling after Chronic Exposure to Ovalbumin in Sensitized Guinea Pigs: Role of Cell Renewal of Airway Resident Cells

We wanted to know whether airway remodeling caused by chronic exposures to antigen differed depending on the degree of maturation of animals. We sensitized guinea pigs at different stages of maturation: juvenile (approximately 200 g in body weight), adult (400 g), and old animals (800 g). Then, animals were repeatedly challenged with inhaled ovalbumin (0.3% or 3%) or vehicle twice a week for 6 wk. After the final challenge, the lungs were excised for the histologic evaluation of changes in the thickness of the inner wall area (Ti), the smooth muscle area (Tm), and the outer wall area (To) in noncartilaginous airway dimensions. To clarify whether or not the observed changes were due to renewal of airway cells, we stained the samples with labeled nucleotide 5′-bromo-2′-deoxyuridine (BrdU), which we injected repeatedly during the challenge periods. Chronic exposures to antigen induced airway wall thickening regardless of their stages of maturation. However, prominent areas of thickening differed between the three groups. Ti increased more remarkably in juvenile and adult animals than in old ones. By contrast, Tm significantly increased only in old animals. BrdU staining revealed more renewal of epithelial cells in juvenile and adult animals than in old ones (juvenile ≧ adult > old), suggesting that increased renewal of epithelial cells contributed to the thickening of Ti in juvenile and adult animals. By contrast, only a slight increase in smooth muscle cell renewal was found even in old animals, indicating that an increase in Tm was due to factors such as hypertrophy. These results show that the development of antigen-induced airway remodeling is partly modified by the degree of maturation of animals in vivo.