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Biomedical subjects

J E Grønbech

Publications and source records attributed to J E Grønbech.

At least 19 recordsLinked to original sources

Hemodynamic and tissue blood flow responses to long-term pneumoperitoneum and hypercapnia in the pig.

BACKGROUND: Increased peritoneal blood flow may influence the ability of cancer cells to adhere to and survive on the peritoneal surface during and after laparoscopic cancer surgery. Carbon dioxide (CO2) pneumoperitoneum is associated with a marked blood flow increase in the peritoneum. However, it is not clear whether the vasodilatory effect in the peritoneum is related to a local or systemic effect of CO2. METHODS: In this study, 21 pigs were exposed to pneumoperitoneum produced with either CO2 (n = 7) or helium (He) (n = 7) insufflation at 10 mmHg for 4 h, or to two consecutive levels of hypercapnia (7 and 11 kPa) (n = 7) produced by the addition of CO2 to the inhalational gas mixture. Tissue blood flow measurements were performed using the colored microsphere technique. RESULTS: Blood flow in peritoneal tissue increased during CO2, but not He, pneumoperitoneum, whereas it did not change at any level of hypercapnia alone. There was no change in blood flow in most organs at the partial pressure of CO2 (PaCO2) level of 7 kPa. However, at a PaCO2 of 11 kPa, blood flow was increased in the central nervous system, myocardium, and some gastrointestinal organs. The blood flow decreased markedly in all striated muscular tissues during both levels of hypercapnia. CONCLUSION: The effect of CO2 on peritoneal blood flow during laparoscopic surgery is a local effect, and not attributable to central hemodynamic effects of CO2 pneumoperitoneum or high systemic levels of CO2.

Animals↗

ECL cell histamine mobilization and parietal cell stimulation in the rat stomach studied by microdialysis and electron microscopy.

AIM: Gastrin stimulates acid secretion by mobilizing histamine from enterochromaffin-like (ECL) cells that occur predominantly at the base of the gastric glands. The parietal cells occur higher up in the glands nearer to the gastric lumen. The present study was performed to assess whether histamine is transported from the ECL cell via the microcirculation (endocrine route) or local diffusion (paracrine route). METHODS: Totally isolated, vascularly perfused, rat stomachs were examined both in basal and gastrin-stimulated state. Histamine concentrations, determined by radioimmunoassay in venous effluent and microdialysate from an indwelling probe in the submucosa, were monitored over a period of 240 min. Gastrin-17 was infused through an arterial catheter for 120 min. The parietal cells were examined by electron microscopy, and the percentage of actively secreting parietal cells (displaying secretory canaliculi) in four regions along the glands (basal to surface, zones I-IV) was determined. RESULTS: Gastrin stimulated acid secretion and histamine release as well as parietal cell activation. Upon gastrin stimulation, histamine concentration in the microdialysate was 2.5-fold higher than in the venous effluent (P = 0.008). The parietal cells in the upper part of the gland (zone III) were found to be activated the most. CONCLUSION: As the histamine concentrations were higher in the tissue (microdialysate) than in blood, histamine seems to reach the parietal cells via the paracrine route. The fraction of active parietal cells seems to depend more on the age of the parietal cells than on the distance from the ECL cell.

Animals↗

Effect of carbon dioxide pneumoperitoneum on tissue blood flow in the peritoneum, rectus abdominis, and diaphragm muscles.

BACKGROUND: Changes in local blood flow may play a role in the pathogenesis of port-site metastasis. This study aimed to investigate the effect of pneumoperitoneum induced by carbon dioxide (CO2) on the blood flow in the peritoneum and abdominal wall muscle layers, which are target structures for this phenomenon. METHODS: The study was performed on domestic farm swine of both genders weighing 20 to 25 kg. Intraabdominal pressures (IAP) of 0, 5, and 10 mmHg were produced by either CO2 ( n = 9) or helium (He) ( n = 6) insufflations. The colored microsphere technique was used to measure blood flow distributions in the parietal peritoneum, rectus abdominis, and diaphragm muscles. RESULTS: Insufflation of CO2 was associated with a threefold increase in blood flow of the parietal peritoneum at both 5 and 10 mmHg IAP ( p < 0.001 for both pressure levels). In contrast, insufflation of He caused a significant decrease in blood flow in the parietal peritoneum at both 5 and 10 mmHg ( p < 0.05). In the rectus abdominis and diaphragm muscles, blood flow remained unchanged after insufflation of CO2 at both 5 and 10 mmHg IAP. However, after insufflation of He, there was a substantial decrease in blood flow both in the rectus abdominis and diaphragm muscles at both 5 mmHg ( p < 0.01 and p < 0.05, respectively) and 10 mmHg ( p < 0.001 and p < 0.01, respectively). CONCLUSIONS: Despite high intraabdominal pressure, tissues surrounding the abdominal cavity, particularly the peritoneum, respond to insufflation of CO2 with increased blood flow, which may favor the growth of tumor cells.

Animals↗

Effect of increased intraabdominal pressure on cardiac output and tissue blood flow assessed by color-labeled microspheres in the pig.

BACKGROUND: Studies of the hemodynamic effects associated with the pneumoperitoneum have had controversial results. We set out to investigate the effect of increased intraabdominal pressure (IAP) on cardiac output and tissue blood flow in various intraabdominal and extraabdominal organs using the color-labeled microsphere (CLM) technique. METHODS: IAP was induced by CO2 insufflation in anesthetized pigs; 0, 5, and 10 mmHg was used in the low-pressure group and 0, 15, and 24 mmHg in the high-pressure group. Tissue blood flow (ml.min-1.g-1) and cardiac output (CO) (ml/min) were determined by the CLM technique. RESULTS: CO decreased at IAP > or = 15 mmHg. Arterial PaCO2 and hydrogen ion concentration increased in response to all levels of IAP. Arterial PaO2, oxygen saturation, and bicarbonate ion concentration remained unchanged. Low IAP did not influence tissue blood flows in most of the organs. However, in the spleen, pancreas, esophagus, and gastric mucosal specimens, tissue blood flow was significantly decreased at 24 mmHg. CONCLUSION: The level of IAP used in current practice (10-12 mmHg) appears to be safe with regard to hemodynamic variables and tissues blood flow; however, higher levels may induce a decrease in cardiac output and tissue blood flow.

Animals↗

Mast cells are involved in the gastric hyperemic response to acid back diffusion via release of histamine.

Acid back diffusion into the rat stomach mucosa leads to gastric vasodilation. We hypothesized that histamine, if released from the rat mucosa under such conditions, is mast cell derived and involved in the vasodilator response. Gastric blood flow (GBF) and luminal histamine were measured in an ex vivo chamber. Venous histamine was measured from totally isolated stomachs. Mucosal mast cells (MMC), submucosal connective tissue mast cells (CTMC), and chromogranin A-immunoreactive cells (CgA IR) were assessed morphometrically. After mucosal exposure to 1.5 M NaCl, the mucosa was subjected to saline at pH 5.5 (control) or pH 1.0 (H(+) back diffusion) for 60 min. H(+) back diffusion evoked a marked gastric hyperemia, increase of luminal and venous histamine, and decreased numbers of MMC and CTMC. CgA IR cells were not influenced. Depletion of mast cells with dexamethasone abolished (and stabilization of mast cells with ketotifen attenuated) both hyperemia and histamine release in response to H(+) back diffusion. GBF responses to H(+) back diffusion were attenuated by H(1) and abolished by H(3) but not H(2) receptor blockers. Our data conform to the idea that mast cells are involved in the gastric hyperemic response to acid back diffusion via release of histamine.

Acids↗

Oxyntic lesions may be provoked in the rat both by the process of acid secretion and also by gastric acidity.

BACKGROUND: Gastric ischaemia appears to be a common pathogenetic factor for stress ulcers. These ulcers occur predominantly in the oxyntic mucosa, suggesting that the acid secretory process or its stimulation is involved in the pathogenesis. METHODS: We examined separately the role of the acid secretory process and gastric luminal acidity in the pathogenesis of gastric lesions using the isolated vascularly perfused acid-secreting rat stomach. RESULTS: Pentagastrin-stimulated acid secretion induced submucosal bleeding in the oxyntic mucosa whether accompanied by perfusion of the gastric lumen with saline or a phosphate buffer at pH 7.0. On the other hand, acidity, whether endogenous or introduced by luminal perfusion, induced erosions in both the oxyntic and antral mucosa. CONCLUSION: It is concluded that the acid secretory process itself contributes to the particular vulnerability of the oxyntic mucosa to ischaemia. Histamine released upon stimulation of gastric acid secretion or shortage of energy due to the requirements for acid secretion may both contribute to this vulnerability. Furthermore, these findings suggest that inhibition of gastric acid secretion should be superior to antacids in preventing stress ulcers.

1-Methyl-3-isobutylxanthine↗

Acute erosions of the gastric mucosa in burned rats: effect of sucralfate.

The effect of intragastric sucralfate on development of gastric erosions in burns was studied in 20 rats anaesthetised with midazolam/fentanyl/fluanisone. Gastric blood flow was measured by radioactive microspheres immediately before, and 20, 40, and 120 minutes after the rats had been burned. Significantly fewer erosions were found in the 10 rats treated with sucralfate (less than 2% of the gastric mucosal surface was affected) compared with the controls (16% of the mucosa affected). There was no difference in the rate of gastric blood flow in any part of the stomach between the rats treated with sucralfate and the controls. We conclude that sucralfate is effective in preventing gastric erosions in burned rats, but that other mechanisms of action than increase gastric blood flow are responsible for its protective effect.

Animals↗

Role of sensory afferent neurons in hypertonic damage and restitution of the rat gastric mucosa.

BACKGROUND & AIMS: Gastric mucosal hyperemia is a protective response mediated at least in part by the response of sensory afferent neurons to hydrogen ions. The aim of this study was to determine if other pathways to the hyperemic response are present and if these neurons have an effect exclusive of hyperemia on mucosal protection and repair. METHODS: Rat sensory afferent neurons were ablated by capsaicin treatment. Chambered stomachs were damaged by hypertonic saline followed by either acidic or neutral isotonic saline. Blood flow was measured by laser Doppler velocimetry, and mucosal morphology was quantitatively evaluated by microscopy. RESULTS: Mucosal damage alone evoked a strong hyperemic response in both control and ablated rats. Ablated rats lost gastric protection despite this hyperemic response. Acid exposure after damage sustained the hyperemic response. Rapid epithelial restitution occurred faster (even over hemorrhagic lesions) in control rats. CONCLUSIONS: The hyperemic response to mucosal damage alone is not mediated by sensory neurons. Protection of the stomach by sensory afferent neurons occurs by mechanisms also unrelated to their elicitation of hyperemia. Restitution during acid challenge is enhanced by the sustained hyperemic response mediated through sensory afferent neurons.

Animals↗

Role of gastric blood flow in impaired defense and repair of aged rat stomachs.

To study impaired gastric mucosal tolerance against noxious agents in aged rats, possible factors underlying this observation were compared in anesthetized Fisher 344 young and aged rats. The gastric mucosa was damaged by in situ exposure to 80% ethanol for 30-45 s and by 1 M NaCl for 10 min followed by saline (pH = 1.0) for 60 min in chambered stomachs. The lesion area was significantly larger and epithelial restitution was significantly slower in aged than in young rats after both types of injury. Changes in gastric blood flow were monitored by laser-Doppler velocimetry. Young, but not aged, rats showed a marked increase in gastric blood flow in response to 1 M NaCl, acid challenge, and 640 microM capsaicin for 60 min. Young rats showed a higher density of calcitonin gene-related peptide (CGRP)-staining nerve fibers around submucosal blood vessels and higher mucosal release of prostaglandin E2 and leukotriene C4 than did aged rats. These data suggest that impaired mucosal defense and reduced restitution in aged rats is related to lack of hyperemic response caused by mucosal injury and H+ back-diffusion, which is probably due to decreased density of CGRP-staining nerve fibers and prostaglandin biosynthetic capacity in the mucosa.

Aging↗

Burst abdomen and incisional hernia after major gastrointestinal operations--comparison of three closure techniques.

OBJECTIVE: To compare the incidence of burst abdomen and incisional hernia after three different techniques of closure of the abdominal wall after major gastrointestinal operations. DESIGN: Prospective, randomised, controlled trial. SETTING: University hospital, Norway. SUBJECTS: 599 adults who underwent major operations for gastrointestinal conditions between December 1990 and February 1992. INTERVENTIONS: Patients were randomised in three groups for abdominal wall closure by continuous mass polyglyconate (Maxon) double suture with loop, continuous mass polyglactin 910 (Vicryl), and interrupted polyglactin 910 (Vicryl) (layered for transverse and mass for midline incisions). MAIN OUTCOME MEASURES: Burst abdomen during the postoperative period, and incisional hernia after one year follow up. RESULTS: The incidence of wound dehiscence was 2% and of incisional hernia at one year 7%. There were no differences in the rate of dehiscence among the groups, but there were significantly more hernias in the polyglyconate group (19/164, 12%) compared with the two in which polyglactin 910 was used (16/327, 5%). Wound infections developed in 84/583 of our patients (14%) and the incidence was closely associated with emergency operations and contamination. Wound complications were not associated with the closure technique. CONCLUSIONS: Wound infection is the most important single factor in the development of burst abdomen and incisional hernia. The continuous closure technique is quicker, cheaper, and as safe as the interrupted technique.

Aged↗

Morbidity, ability to swallow, and survival, after oesophagectomy for cancer of the oesophagus and cardia.

OBJECTIVE: To study survival, morbidity, and ability to swallow, after oesophagectomy for cancer of the oesophagus and cardia. DESIGN: Prospective open study. SETTING: University hospital, Norway. SUBJECTS: 83 patients, 38 with squamous cell carcinoma and 45 with adenocarcinoma of the oesophagus and cardia. INTERVENTIONS: Transhiatal (n = 51) and transthoracic (n = 32) oesophagectomy. Oesophageal replacement was by either stomach (n = 80) or colon (n = 3). Cervical anastomosis was used in all but 2. MAIN OUTCOME MEASURES: Early and late morbidity and mortality, length of stay in intensive care unit and in hospital, and survival analysis. RESULTS: 30 Day and in hospital mortality were 0 and 4% for transhiatal, and 6% and 9% for transthoracic, oesophagectomy. Complications included recurrent nerve palsy (n = 7), anastomotic leaks (n = 5), and chylothorax (n = 4). 17 Patients (22%) needed dilatations for stenosis of the anastomosis, and 71 (85%) of the patients left hospital within four weeks of operation. Survival analysis showed a 5 year survival rate of 33% for patients with adenocarcinoma operated on for cure and a 2 year survival of 28% for patients with squamous cell carcinoma. CONCLUSIONS: Oesophagectomy for cure is worthwhile as some patients are cured and most of the remainder have prolonged relief of their dysphagia. Palliative resections should not be done in patients with distant metastases or invasion of adjacent organs by the tumour because of long stay in hospital, appreciable morbidity, and short life expectancy.

Adenocarcinoma↗

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.

Animals↗

Gastric mucosal repair and release of HCO3- after damage by 2 M NaCl in cat: role of systemic acid base status.

To study the influence of acid base balance on gastric mucosal repair, NH4Cl or NaHCO3 was given intravenously to anesthetized cats after mucosal damage induced by intraluminal 2 M NaCl. Saline at pH 5 or 1 was perfused via an oral tube through the stomach lumen and evacuated via a pyloric tube to a chamber with pH and PCO2 electrodes. Luminal bicarbonate (HCO3-) was markedly increased early after damage in both acidotic and alkalotic animals. In alkalotic animals mucosal blood flow increased about twofold in response to mucosal damage, whereas the early hyperemic response was either completely attenuated or blunted in acidotic animals. HCO3- release was correlated to availability of HCO3- by blood in alkalotic animals with luminal pH 5. Alkalotic animals showed improved repair compared with acidotic animals, and mucosal restitution was correlated to availability of HCO3- by blood. We conclude that luminal leakage of HCO3- or plasma after mucosal damage depends on availability by blood and consumption of HCO3- within the mucosa and that blood borne HCO3- has a major influence on gastric mucosal repair.

Acid-Base Equilibrium↗

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.

Animals↗

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.

Animals↗

[Crohn disease. Diagnosis and treatment].

Crohn's disease was the topic of a meeting of gastroenterologists in Bergen last year with the purpose of working out consensus guidelines for diagnosis and treatment of this chronic disease. The most important diagnostic procedures are radiology, gastrointestinal endoscopy and histopathology. Transmural, segmental involvement is characteristic, whereas granulomas are found in only 25% of biopsy specimens. Corticosteroids are effective in active Crohn's disease located to all parts of the intestine, whereas sulfasalazine and metronidazole are most effective in Crohn's colitis. Azathioprine and 6-mercaptopurine should be reserved for patients with chronic active disease that is unresponsive to steroids or requires higher doses. Azathioprine also has a prophylactic effect. Surgery is indicated in patients whose quality of life is diminished in spite of adequate medical treatment, in patients with bowel or ureter stenosis, fistula or abscess, and in patients with acute perforation or toxic dilatation. Limited resection is recommended, and stricture plasty can be alternative to extensive resection.

Crohn Disease↗

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.

Animals↗