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Biomedical subjects

W A Mersereau

Publications and source records attributed to W A Mersereau.

At least 19 recordsLinked to original sources
PubMed1989

Neomycin prevents indomethacin-induced gastric peristalsis and mucosal injury in the rat.

Inhibition of prostaglandin synthesis together with vagally mediated peristaltic contractions are essential if mucosal injury is to occur in the stomach of indomethacin-treated rats. The neomycin group of antibiotics has been shown to interfere with acetylcholine release. Agents blocking peristalsis have been demonstrated to prevent mucosal injury. We postulated that neomycin might inhibit peristalsis and prevent lesion formation. The effect of oral neomycin and bacitracin on gastric wall tone and peristaltic response to indomethacin were assessed and related to the lesion score. Bacitracin had no effect on either response and severe injury occurred. Neomycin did not block the tonal response to indomethacin but abolished peristalsis and no injury occurred. Induction of peristalsis with insulin in neomycin-indomethacin treated rats restored mucosal injury. It is concluded that neuromuscular blockade by neomycin prevented mucosal lesions by preventing peristalsis and not by impairing the ability of indomethacin to inhibit prostaglandin synthesis.

Animals↗
PubMed1988

Relationship between the gastric myoelectric and mechanical activity in the genesis of ulcers in indomethacin-insulin-treated rats.

We have proposed that gastric contractile activity mechanically induces ulcers in the nonsteroid antiinflammatory drug (NSAID)-treated rat. This study examines first the relationship between number (dose) of peristaltic contractions applied to the mucosa and the ulcer score. Second, it examines the relative roles of: altered gastric myoelectrical activity (MEA) resulting from indomethacin (Indo) pretreatment, insulin-induced gastric peristalsis, and a combination of the two in the generation of mucosal lesions. Third, it examines the effect of exogenous prostaglandin on the Indo-altered MEA and relates it to ulcerogenesis. Indo pretreatment increased gastric tone and MEA. In such animals, the dose of peristaltic contractions applied to the gastric wall was related to the ulcer score in a dose-dependent manner. Exogenous prostaglandin (PG) reversed the MEA effect of Indo and reduced ulceration. It is postulated that an altered smooth muscle state secondary to inhibition of prostaglandin synthesis (PG-S) renders the mucosa vulnerable to injury by peristaltic action.

Animals↗
PubMed1988

Relative roles of acid and mucosal compression in ulcerogenesis in indomethacin-insulin-treated rat.

We have proposed that gastric peristaltic activity is primarily responsible for ulcerogenesis in the phenylbutazone-treated rat and that acid plays only a synergistic role. This study examines the effect of graded doses of the H2 blocker cimetidine on acid secretion and ulcerogenesis occurring during insulin-induced peristalsis in the indomethacin (Indo) -pretreated rat. The second part of the study utilizes graded gastric distension with exogenous acid to examine the role of the forceful apposition of the mucosal folds during peristalsis in lesion genesis. It is demonstrated that the inhibition of acid secretion by cimetidine reduces but does not prevent ulceration. Gastric inflation with acid obliterates mucosal folding, prevents mucosal apposition during peristalsis, and abolishes ulcerogenesis. It is concluded that mucosal compression is the primary cause of the linear lesions along the base of the mucosal folds but that acid is necessary to extend the lesions once initiated.

Animals↗
PubMed1988

Progesterone receptors regulate gallbladder motility.

The increased incidence of gallstones in multiparous women may be related to hormonal effects on the gallbladder and its contractility. The occurrence of estrogen and progesterone receptors were studied in the gallbladders of three groups of female guinea pigs (normals, oophorectomized, and oophorectomized treated with estrogen + progesterone for 14 days). Gallbladder contractile response in vivo to cholecystokinin (CCK) was related to the presence of these receptors. The gallbladders from normal females showed low progesterone and estrogen binding activity (4.9 +/- 2.0 and 2.4 +/- 0.8 fmoles/mg cytosol protein). Oophorectomized females had no detectable progesterone or estrogen receptors, but after treating oophorectomized females for 14 days with estrogen + progesterone, gallbladder concentrations of progesterone receptors increased significantly to 14.7 +/- 5.9 fmoles/mg and estrogen binding activity was minimally detectable at 1.4 +/- 0.8 fmoles/mg. The gallbladder contractile response to CCK was inversely related to the concentration of progesterone receptors in the gallbladder wall. These data suggest that the gallbladder contains progesterone receptors which are susceptible to circulating hormonal conditions and which have a regulatory effect on gallbladder contractility.

Animals↗
PubMed1988

A simplified alloperfused rat heart model for studying myocardial protection.

Isolated hearts are widely used to study myocardial protection because they allow for rigorous control of parameters that is not readily achievable by the in-vivo heart models. The classic Langendorff system and its modifications using asanguinous perfusates have an obvious limitation in that asanguinous reperfusion is clinically irrelevant. The available blood-perfused heart systems are complicated by the use of pumping circuits. In this study, an isolated rat heart, harvested under cold cardioplegia, is alloperfused with the blood coming from an isogenic support rat. The coronary effluent returns to the support rat by gravity. The model was validated by testing its response to normothermic ischemia and reperfusion, and the expected protective effects of hypothermic-cardioplegia are demonstrated. A marked difference in response to ischemia is shown between this model and the buffer-perfused heart. We conclude that alloperfused isolated rat heart model is an inexpensive and more clinically relevant method of screening various new modes of myocardial protection.

Animals↗
PubMed1982

Prevention of phenylbutazone ulcer in the rat by glucose: role of a glycoprivic receptor system.

The mechanism by which the extragastric administration of phenylbutazone (PBZ) and other nonsteroid anti-inflammatory drugs induce a vagally mediated gastric hypercontractile response and ulceration is unknown. Glucose administration has been reported to protect the rat and the monkey from the ulcerogenic action of aspirin. It was postulated that by uncoupling oxidative phosphorylation PBZ might stimulate an energy-sensitive receptor system that results in the gastric contractile response. Glucose feeding or intravenous infusion was seen to prevent or abolish the gastric contractile response to the intraileal injection of 22.5 mg of PBZ in cervical-sectioned rats with miniature gastric balloons. Glucose treatment also significantly reduced ulceration and hemorrhage. Fructose infusion was somewhat less effective. Mannitol infusion had no effect on the PBZ-induced gastric contractile activity, and all animals developed severe ulceration and hemorrhage. Blood glucose levels fell significantly in starved rats treated with PBZ. Glucose feeding and glucose or fructose infusion prevented or reduced this effect. It is suggested that by alleviating the "glucoprivic state" induced by PBZ glucose abolishes the gastric contractile response and prevents ulceration and hemorrhage.

Animals↗
PubMed1982

Role of gastric mucosal folds in formation of focal ulcers in the rat.

Ulcers induced in rats by a variety of techniques often have a characteristic elongated shape or are focal and follow a linear pattern. The reason for this is unknown but may be related to the presence of gastric mucosal folds. Studies utilizing a rat gastric chamber preparation demonstrate that the apex of the mucosal fold is peculiarly sensitive to injury by corrosive agents in normotensive or hypotensive animals and in the completely ischemic mucosa. Focal gastric mucosal potential difference (PD) measurements utilizing a "sucrose gap" technique demonstrate that the PD at the crest of a mucosal fold is significantly lower than in the trough at the base of the fold, suggesting a local perfusion or permeability defect. The stomachs of animals submitted to three different ulcerogenic treatment demonstrated significantly more fold-related lesions that nonfold lesions. It is concluded that although different mechanisms may be responsible for the grossly different lesions, the mucosal fold, for a variety of reasons, appears particularly sensitive to injury.

Action Potentials↗
PubMed1981

Synergism between acid and gastric contractile activity in the genesis of ulceration and hemorrhage in the phenylbutazone-treated rat.

The nonsteroid anti-inflammatory drugs including phenylbutazone produce significant gastric ulceration and hemorrhage even when administered by an extragastric route. To investigate the mechanism involved, cervical sectioned rats received an intraileal injection of phenylbutazone as the sodium salt in methylcellulose. Gastric contractile activity as recorded with a miniature gastric balloon, and the stomach was perfused with either acid at pH 1 or buffer at pH 7. Rats receiving phenylbutazone developed a pattern of abnormally strong contractile activity that began 60 to 90 minutes after drug administration. The contracting stomachs of rats perfused with acid developed significantly more ulceration and bled more severely than buffer-perfused rats. Vagotomy or atropine prevented the gastric contractile response to phenylbutazone, and such rats failed to develop significant ulceration in spite of the fact that their stomachs were perfused with acid. Cervical sectioned rats treated with methylcellulose alone failed to develop the abnormal contractile pattern and showed no significant gastric injury or hemorrhage. It is concluded that the focal hemorrhagic lesions induced by the extragastric administration of phenylbutazone in the rat are the result of mucosal compression at specific sites secondary to the passage of extremely strong peristaltic waves. They are vagally mediated and although the presence of acid does not appear essential for their initiation, it plays a synergistic role in their development and hemorrhage.U

Animals↗
PubMed1978

Interactions of gastric blood flow, barrier breaker, and hydrogen ion back diffusion during ulcer formation in the rat.

A rat gastric chamber preparation was used to determine the interrelations between H+ back diffusion, mucosal blood flow, the area of mucosa treated with bile salts and ulcer formation. The rate of H+ back diffusion was found to be dependent on both mucosal blood flow and the area of mucosa exposed to bile salts. It is concluded that, although H+ back diffusion is a convenient measure of barrier permeability under conditions of normal mucosal blood flow, during mucosal ischemia this parameter fails to reflect permeability because of decreased mucosal clearance of H+. These findings would explain apparent controversy whereby ulceration occurs under shock conditions in the absence of apparent H+ back diffusion.

Animals↗
PubMed1978

"Sucrose gap" technique for measurement of focal gastric mucosal potential differences in the rat.

Bile salts, mechanical trauma, and ischemia were used to produce focal alterations in rat gastric mucosa in a chamber preparation. Gastric mucosal to serosal potential difference (PD) was measured from both treated and untreated areas using electrodes in contact with the mucosal surface. The sensitivity of the measurements was increased if a nonconducting solution (isotonic sucrose) was used to isolate electrically the control from the experimental sites. This "sucrose gap" technique thus allows the identification of focal areas of gastric mucosa with an altered PD. In addition, this technique was used to measure the PD of the forestomach, fundus, and antrum of the rat, and to demonstrate that atropine and pentagastrin influence the PD only in the fundus.

Animals↗
PubMed1974

Prevention of bile reflux-induced acute gastric ulceration in the rat by cholestyramine.

The role of bile salts and refluxed duodenal content in the pathogenesis of acute gastric ulcers in the shocked rat were examined. The addition of cholestyramine to duodenal contents inhibits their ulcerogenic action in the stomach of rats challenged by an acid load, (100 mEq/l Hcl) and subsequently bled to a mean blood pressure of 20 mm Hg. Also, bile duct ligation 2 days before the reflux procedure and subsequent shock also inhibited ulcer formation. An ex vivo rat gastric chamber was used to further demonstrate that the "barrier" breaking action of bovine sodium taurocholate and sodium lauryl sulphate could be prevented by cholestyramine. Cholestyramine also inhibited the usual rapid depression of the transmucosal potential difference (PD) produced by both of these agents. It is concluded that cholestyramine protects the gastric mucosa from ulceration by blocking the barrier breaking action of bile salts in duodenal chyme.

Bile Acids and Salts↗