Jon Erik Grønbech

Role of blood flow in adaptive protection of the cat gastric mucosa

This study was designed to test the hypothesis that adaptive cytoprotection is related to increased blood flow caused by mild irritants. The stomach of cats was perfused with saline at pH 1.0. Mucosal blood flow was determined by radioactive microspheres, and celiac artery blood flow was measured by Doppler ultrasound. Gastric blood flow was left undisturbed or reduced by tightening a vessel loop around the celiac artery. Mucosal exposure to absolute ethanol for 2 minutes caused extensive damage to the surface epithelium, the pits, and the upper half of the glands. Pretreatment of the mucosa with 2 mol/L NaCl for 10 minutes prevented the development of mucosal lesions after subsequent application of absolute ethanol. The mucosal blood flow increased markedly after treatment with 2 mol/L NaCl. When this hyperemic response was inhibited by reducing celiac artery blood flow, ethanol caused lesions of similar degree as in animals not pretreated with 2 mol/L NaCl. A highly significant correlation was obtained between mucosal blood flow, as determined just before the application of ethanol, and the degree of ethanol-induced damage. At a chosen level of blood flow, ethanol caused the same degree of damage with or without pretreatment with 2 mol/L NaCl. In conclusion, high mucosal blood flow caused by a mild irritant is an important factor in adaptive gastric protection. With the present experimental setup, the protection could be fully explained as a result of the hyperemic response caused by 2 mol/L NaCl.

Distribution of cardiac output during pentobarbital versus midazolam/fentanyl/fluanisone anaesthesia in the rat.

Differences in effects on central haemodynamics, organ blood flow, and serum corticosterone were studied in 11 rats anaesthetized with midazolam/fentanyl/fluanisone (MFF) and 11 other rats anaesthetized with sodium pentobarbital. Compared with pentobarbital, MFF reduced aortic blood pressure by 25%, increased heart rate by 20%, and increased cardiac output by 80%. Unlike most tissues, MFF produced a fivefold increase in blood flow to skeletal muscle, and decreased adrenal blood flow compared to pentobarbital anaesthesia. Initial serum corticosterone levels were lower in rats given MFF anaesthesia, indicating better stress protection. This study also indicates that MFF anaesthesia is preferable to pentobarbital because tissue perfusion generally was better preserved.

Gastric mucosal repair in the cat: Role of the hyperemic response to mucosal damage

This study concerns the significance for the mucosal repair process of the gastric mucosal hyperemic response after mucosal damage caused by 2 M NaCl. Celiac artery blood flow was measured by Doppler ultrasound and stomach arterial inflow was either left undisturbed or reduced in a controllable fashion by tightening a vessel loop around the celiac artery immediately after mucosal exposure to 2 M NaCl or 150 mM NaCl. The stomach lumen was perfused with saline at pH 1.00 before and after exposure to 2 M NaCl. Gastric mucosal blood flow increased after exposure to 2 M NaCl, and 90 min after mucosal exposure to 2 M NaCl the mucosal surface showed nearly complete restitution of the surface epithelium. In all animals in which mucosal hyperemia was restricted by reducing celiac artery blood flow by 60% after mucosal damage, extensive gastric erosions were present. Similar reduction of celiac artery blood flow in control animals without mucosal damage did not produce visible lesions, and the stomachs proved to be normal by microscopy. These findings show that the gastric mucosal hyperemic response after damage is important for protection of the damaged mucosa during restitution of the gastric surface epithelium.

Role of bicarbonate in blood flow-mediated protection and repair of damaged gastric mucosa in the cat

BACKGROUND/AIMS The hyperemic response after superficial gastric mucosal damage is essential for repair of the mucosa. Only indirect evidence suggests that this is caused by supply of bicarbonate. Therefore, this study tested the effect of maintaining the availability of bicarbonate after prevention of the hyperemic response after damage by 2 mol/L NaCl. METHODS Celiac artery flow was reduced, as monitored by Doppler ultrasonography, by gradual constriction of the vessel after mucosal damage. Saline (pH 1.0) was perfused through the stomach lumen and thereafter through a closed chamber with pH and PCO2 electrodes. RESULTS Exposure to 2 mol/L NaCl produced a marked increase of mucosal blood flow as measured by microspheres (P < 0.025) and a high degree of mucosal restitution 90 minutes after damage as judged by microscopy, whereas prevention of the hyperemic response caused extensive erosions and much less restitution (P < 0.001). The latter effect was completely counteracted by intravenous bicarbonate. High blood concentration of bicarbonate increased luminal release of bicarbonate, whereas high mucosal blood flow did not. CONCLUSIONS These data show that bicarbonate is an important factor in blood flow-mediated protection and repair of damaged gastric mucosa and suggest that concentration gradients are the major determinants for transport of bicarbonate across the damaged and restituted mucosa.

Gastric epithelial restitution at low luminal pH during influence of pentagastrin or cimetidine in the cat

This study examines restitution of the gastric surface epithelium at luminal pH 1 after damage to the gastric mucosa by instillation of 2 M NaCl for 10 min. After mucosal damage, potential difference decreased to zero and H+ back-diffusion increased. Gastric blood flow increased after exposure to 2 M NaCl, irrespective of the secretory state of mucosa. Neither pentagastrin nor cimetidine showed any protective effect against mucosal damage produced by 2 M NaCl. Ninety minutes after mucosal exposure to 2 M NaCl there was an almost complete restitution of the gastric surface epithelium in pentagastrin-stimulated and cimetidine-treated animals, whereas about 15% of the gastric surface still showed damage in animals in which acid secretion was not interfered with. These findings show that restitution of the surface epithelium, in vivo, is a rapid and resistant process even at a very low luminal pH. The secretory state of mucosa may have some influence on this process.

Regional blood flow and acid secretion associated with damage and restitution of the gastric surface epithelium in cats

The gastric mucosa of anesthetized cats was exposed to 2 M NaCl for 10 min. After returning to gastric perfusion with 150 mM NaCl and pH 7.40, with and without pentagastrin stimulation, transmucosal potential difference decreased to zero and then gradually increased to approximately half the original value during the following 90 min. H+ secretion decreased and remained close to zero after exposure to 2 M NaCl in nonstimulated cats, whereas pentagastrin-stimulated secretion gradually increased to nearly half the preexposure level. Mucosal blood flow increased, and the vascular resistance decreased in the posterior wall of the stomach corresponding to epithelial damage, as observed by light microscopy after 15 min. Blood flow during pentagastrin stimulation was initially high in fundus and corpus and did not increase further after exposure to 2 M NaCl, but showed similar changes as without pentagastrin in the antrum. Epithelial restitution occurred within 90 min during both nonstimulated conditions and pentagastrin stimulation. In control animals subjected to 150 mM NaCl there were no changes in transmucosal potential difference, H+ secretion, or blood flow throughout the experiment and epithelial damage was not found. In conclusion, damage caused by 2 M NaCl to the gastric surface epithelium was associated with decreased acid secretion and increased mucosal blood flow. These factors may contribute to creating favorable conditions for the epithelial restitution, indicated by restoration of transmucosal potential difference and observed by light microscopy.

Restituted Gastric Mucosa: Tolerance Against Low Luminal pH and Restricted Mucosal Blood Flow in the Cat

This study examined the tolerance of gastric surface epithelium allowed to restitute for 90 min after damage produced by mucosal exposure to 2 M NaCl for 10 min. Cats were subjected to gastric luminal perfusion with saline at pH = 1.0 and reduction of celiac artery blood flow for 90 min. A flow reduction of 55%, as assessed by Doppler ultrasound flowmetry, was obtained by constriction of the celiac artery. These interventions alone did not produce lesions in nondamaged control cats, whereas exposure to 2 M NaCl immediately before flow reduction evoked extensive erosions as judged by gross examination and microscopy. Stomachs exposed to 2 M NaCl 90 min before flow reduction showed lesions that were clearly less in extent and number than in animals in which an intervening restitution period was not allowed. Topical dimethyl-prostaglandin E2 (50 micrograms/kg) increased the rate by which restituted surface cells were transformed to apparently normal cells. This study shows that the restituted gastric mucosa possesses a remarkably high tolerance against lowered blood flow in the presence of high luminal acidity.

Adaptive Protection Related to Clearance of Ethanol in Gastric Mucosa of Cats

This study was designed to test the hypothesis that hyperemia after exposure to 2 M NaCl protects the gastric mucosa against damage caused by absolute ethanol by removing ethanol diffusing from the gastric lumen into the mucosa. The stomach of anesthetized cats was perfused with saline at pH 1.0. Gastric mucosal blood flow was determined by radioactive microspheres, and portal vein blood flow was measured by Doppler ultrasound flowmetry. The concentration of ethanol in the corpus mucosa and the amount of ethanol transported away from the stomach in portal blood were measured by using absolute ethanol containing trace amounts of 14C-labeled ethanol. Pretreatment with 2 M NaCl for 10 min increased mucosal blood flow and prevented the development of deep mucosal lesions after subsequent application of absolute ethanol. An inverse correlation was found between mucosal blood flow and the degree of ethanol-induced damage. The mucosal content of ethanol was low in animals pretreated with hyperosmolar NaCl, and the degree of mucosal damage was related to the tissue concentration of ethanol. The amount of ethanol transported by blood from the stomach increased with increasing mucosal blood flow. We conclude that the mild irritant, 2 M NaCl, increases mucosal blood flow, which protects the mucosa by removing ethanol diffusing from the lumen. Thus, the mucosal ethanol concentration remains below a level that causes damage.

Release of bicarbonate from damaged and restituted gastric mucosa in the cat

BACKGROUND Gastric mucosal damage leads to luminal alkalinization, but its dependence on mucosal blood flow and acid secretory state of the mucosa is not known. This study examined release of bicarbonate to the gastric lumen and mucosal blood flow in cats after mucosal damage caused by 2 mol/L NaCl and during 90 minutes of epithelial restitution. METHODS Bicarbonate was calculated from measurements of pH and PCO2 in the luminal perfusate. Mucosal blood flow was measured with microspheres. RESULTS Luminal bicarbonate increased more than twofold after damage in pharmacologically nontreated, pentagastrin-treated, and omeprazole-treated animals (P < 0.001). Luminal bicarbonate thereafter decreased completely to pre-damage level in pentagastrin-treated, partly in nontreated, but remained elevated in omeprazole-treated animals. Mucosal blood flow increased about 100% 15 minutes after damage (P < 0.001), irrespective of secretory state. Bicarbonate availability (arterial [HCO(3-)] x mucosal blood flow) was significantly related to luminal release of bicarbonate from the newly damaged (P < 0.01) but not from the restituted mucosa. CONCLUSIONS (1) From the newly damaged mucosa, the luminal release of bicarbonate is related to availability of blood-borne bicarbonate. (2) From acid-stimulated restituted mucosa, the bicarbonate produced by the parietal cells is not released to the lumen, but either consumed within the mucosa by back-diffusing H+ or distributed to the systemic circulation.

Gastric bicarbonate secretion, acid secretion, and mucosal blood flow during influence of pentagastrin and omeprazole in the cat.

In this study secretion of bicarbonate and acid and mucosal blood flow were determined simultaneously in cats. The gastric lumen of anesthetized cats was continuously perfused with isotonic saline. Secretion of HCO-3 and H+ was calculated from continuous measurements of pH and PCO2 in the perfusate. Mucosal blood was measured by means of radiolabeled microspheres. Under resting acid secretory conditions, bicarbonate secretion into the gastric lumen averaged 1.0 mumol/min. Somewhat surprising, both omeprazole (4 mg/kg as bolus) and pentagastrin (16 micrograms/kg.h intravenously) significantly reduced the HCO-3 secretion. Omeprazole did not influence mucosal blood flow, whereas corpus mucosal blood flow increased during pentagastrin stimulation. Under resting acid secretory conditions and during omeprazole treatment there was a close linear relationship between acid and bicarbonate secretion. No such relationship was found during pentagastrin stimulation of the mucosa. No consistent relationship was obtained between blood flow and bicarbonate secretion in normal gastric mucosa.