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Biomedical subjects

L Fändriks

Publications and source records attributed to L Fändriks.

At least 55 records · Page 3Linked to original sources

Sympathetic discharge to mesenteric organs and the liver. Evidence for substantial mesenteric organ norepinephrine spillover.

This study using sampling of blood from the portal vein, in addition to arterial and hepatic sites, to estimate separately spillovers of norepinephrine from mesenteric organs and the liver in seven patients undergoing upper abdominal surgery. Conventional measurements in arterial and hepatic venous plasma provided a measure of net hepatomesenteric NE spillover (403 pmol/ml) that indicated a 13% contribution of these organs to total body spillover of NE into systemic plasma (3,071+/-518 pmol/min). The net hepatomesenteric spillover of NE into systemic plasma was much lower than the spillover of NE from mesenteric organs into portal venous plasma (1,684+/-418 pmol/min). This and the hepatic spillover of NE into systemic plasma (212+/-72 pmol/min) indicated a considerable combined spillover of NE from hepatomesenteric organs (1,896+/-455 pmol/min). The sum of the latter estimate with the difference between total body and net hepatomesenteric NE spillovers provided an adjusted total body spillover of NE into both systemic and portal venous plasma (4,564+/-902 pmol/min). Mesenteric organs made a 37% contribution, and the liver made a 5% contribution to the adjusted total body spillover of NE. Thus, a substantial proportion of total body sympathetic outflow is directed towards mesenteric organs; this is obscured by efficient hepatic extraction of NE (86+/-6%) when measurements are restricted to arterial and hepatic venous plasma.

Aged↗

A mechanism by which Helicobacter pylori infection of the antrum contributes to the development of duodenal ulcer.

BACKGROUND & AIMS: Helicobacter pylori infection and duodenal ulcer disease are firmly correlated. However, the bacteria do mainly colonize the antrum, indicating an indirect pathogenic mechanism. The aim of this study was to test a concept claiming that H. pylori infection of the antrum selectively blocks normal inhibitory reflex pathways to gastrin and parietal cells. METHODS: The effect of antral distention was studied on gastric acid secretion stimulated by pentagastrin and on gastrin release stimulated by gastrin-releasing peptide in H. pylori-infected and noninfected patients with and without duodenal ulcer disease, as well as after eradication of the bacteria. RESULTS: The inhibitory effect on gastric acid secretion induced by antral distention was absent in H. pylori-infected patients irrespective of whether or not they had duodenal ulcer disease. The inhibitory mechanism was restituted in 8 of 10 patients within 9 months after successful eradication of H. pylori infection. Similar results were obtained in studies on gastrin release. CONCLUSIONS: H. pylori infection blocks normal, physiological inhibitory mechanisms from the antrum to both the gastrin cells and to the parietal cell region, resulting in increased gastrin release and impaired inhibition of gastric acid secretion, which will probably lead to an increased duodenal acid load as a general prerequisite for the development of duodenal ulcer disease.

Adult↗

Mechanisms behind changes in gastric acid and bicarbonate outputs during the human interdigestive motility cycle.

Human gastric interdigestive acid and bicarbonate outputs vary cyclically in association with the migrating motor complex (MMC). These phenomena were studied in 26 healthy volunteers by constant-flow gastric perfusion, with continuous recording of pH and Pco2 in mixed gastric effluent and concomitant open-tip manometry of gastroduodenal motility. Stable acid and bicarbonate outputs were registered during less than 50% of the MMC cycle. Acid secretion started to increase 71 +/- 3% into the cycle, with maximum output during antral phase III. Bicarbonate output increased biphasically 1) 40 +/- 5% into the cycle, coinciding with reflux of bile, and 2) at the end of duodenal phase III when the aspirate was devoid of bile. The bicarbonate peak associated with phase III was abolished by atropine (0.01 mg/kg iv, n = 8) and by pyloric occlusion (n = 9) but remained unchanged after omeprazole (n = 10). The acid peak was abolished by both atropine and omeprazole. It is concluded that the MMC-related changes in acid and alkaline outputs represent two different and independent phenomena. Acid secretion cyclicity is due to periodical variations in cholinergic stimulation of the parietal cells. In contrast, the phase III-associated increase in bicarbonate output is due to duodenogastric reflux.

Adolescent↗

Continuous measurement of gastric nitric oxide production.

With the use of a double-lumen catheter, nitric oxide (NO) was dialyzed across a Gore-Tex membrane into a gas phase and subsequently analyzed on-line by chemiluminescence. This new technique for the continuous measurement of NO was evaluated bench-side and applied in the human stomach in vivo to measure the nonenzymatic formation of NO generated from nitrite in an acidic milieu. A linear relation (r2 = 0.991, P < 0.0001) between concentrations of NO in aqueous solutions (2.5-52.5 mM) and NO in the corresponding gas phases obtained by the dialysis technique (50-1,000 parts per billion) validated the present method for quantitative analyses of NO. Interassay and intra-assay coefficients of variation at all concentrations of NO for six experiments were < 5%. High intragastric concentrations of NO (in the micromolar range) were found during basal conditions. The requirement of both nitrite from the saliva and an acidic environment for NO formation is indicated, since depletion of saliva as well as acid neutralization greatly reduced gastric NO concentrations. Furthermore, large amounts of gastric NO were formed after intake of sodium nitrate. With the use of this technique, NO can be continuously measured with accuracy experimentally and clinically in any organ accessible to intubation.

Adult↗

Splanchnic and renal sympathetic activity in relation to hemodynamics during isoflurane administration in pigs.

The aim of the present study was to investigate the impact of isoflurane on regional neurogenic mechanisms in the control of vascular tone. Therefore, regional determinations of sympathetic activity and hemodynamics were made in chloralose-anesthetized swine before and during administration of 1.4% isoflurane. Sympathetic activity was examined from spillover of norepinephrine (NE) into the circulation using an isotope dilution technique. Administration of isoflurane caused a marked decrease in mesenteric (65 +/- 9 pmol.min-1.100 g-1; P < 0.05) NE spillover. Renal NE spillover was moderately decreased (25 +/- 6 pmol.min-1.100 g-1; P < 0.05), whereas liver NE spillover did not change significantly during isoflurane administration, suggesting that liver sympathetic activity is maintained at this level of isoflurane anesthesia. Total body NE spillover decreased (13 +/- 2 pmol.min-1.100 g-1, P < 0.05). Thus, isoflurane affected sympathetic outflow in a regionally differentiated pattern. Significant correlations were found between total body, mesenteric, and renal NE spillovers and vascular resistances, supporting the concept that the observed reductions in vascular resistances in these circulations during isoflurane administration were in part a consequence of reduced sympathetic outflow. In the liver circulation, no correlation was found between NE spillover and liver portal or liver arterial vascular resistances. Liver arterial resistance was significantly reduced during isoflurane administration while liver portal resistance was unchanged. Administration of isoflurane caused reductions in cardiac output, renal, portal, hepatic arterial, and total hepatic blood flows, whereas mesenteric blood flow was unchanged. To summarize, isoflurane decreased mesenteric and renal NE spillover with concomitant reductions in vascular resistances.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Sympatho-adrenergic inhibition of basal and acid-induced changes in duodenal motility, mucosal net fluid and alkaline secretion in the anaesthetized cat.

Experiments were performed on chloralose anaesthetized cats. A 2-cm segment of the proximal duodenum was isolated between two luminally situated balloons and perfused with isotonic saline containing [14C]-PEG 4000 as a non-absorbable marker. The perfusate was analysed with regard to alkalinity (back titration) and concentration of marker (liquid scintillation). Net alkalinization and net fluid transport were calculated with conventional equations. Motor activity in the duodenal wall was recorded as changes in volume of the proximal balloon. In presence of sympathetic neural activity (spontaneous or electrically stimulated) basal motor activity and mucosal alkaline secretion was low and increased minimally in response to luminal HCl (30 mM). Net fluid transport was in an absorptive state and shifted to a small secretion upon the acid-exposure. Subsequent to bilateral acute splanchnicotomy, or the administration of the adrenolytic guanethidine (3-4 mg kg-1, i.v.), spontaneous duodenal contractions occurred and the alkaline secretion was increased. Furthermore, both parameters were then markedly stimulated by luminal perfusion with 30 mM HCl. Basal net fluid transport was zero and turned into secretion upon the acid-exposure. No morphological changes of the duodenal surface epithelium could be detected. The study demonstrates the existence of splanchnic nerve-mediated, adrenergic inhibition of basal, as well as of acid-induced duodenal motility, fluid and alkaline secretion.

Animals↗

Hepatomesenteric release and removal of norepinephrine in swine.

Release and removal of norepinephrine (NE) by hepatomesenteric organs in anesthetized swine were examined using measurements of NE in arterial, portal, and hepatic venous plasma. NE spillover from the liver and mesenteric organs increased during splanchnic nerve stimulation, validating these measurements as indexes of sympathetic outflow. Administration of the neuronal uptake-blocking drug desipramine reduced mesenteric NE extraction more than hepatic extraction, suggesting that neuronal uptake was more important for NE removal in mesenteric organs than in the liver. Circulating NE was removed by the liver more efficiently than by mesenteric organs, whereas mesenteric NE spillover (2.46 nmol/min) exceeded liver NE spillover (0.74 nmol/min). Hepatomesenteric NE spillover represented 53% of total body spillover; NE clearance was 42% of total body clearance. Because of efficient hepatic extraction of NE released by mesenteric organs, the sum of mesenteric and hepatic NE spillovers (3.20 pmol/min) exceeded net hepatomesenteric spillover estimated using arterial and hepatic venous measurements alone (1.96 pmol/min). Thus valid assessment of the substantial amounts of NE released by hepatomesenteric organs requires separate examination of mesenteric and hepatic spillovers.

Animals↗

Gastric output of IgA in man: relation to migrating motility complexes and sham feeding.

BACKGROUND/AIMS: The immunologic reactivity of the gastric mucosa is poorly understood. The origin and dynamics of immunoglobulin A (IgA) occurring in the gastric lumen were investigated in healthy, Helicobacter pylori-negative volunteers. METHODS: Gastroduodenal manometric motility recordings were combined with gastric luminal perfusion, enabling calculation of gastric acid output and analysis of the total IgA output. RESULTS: Acid output and total IgA correlated with the migrating motility complexes (MMC). The gastric IgA release showed maximal values in association with gastric motility phase III (maximal motor activity) and lowest values during phases I and II (none or irregular motor activity). The IgA output correlated with neither swallowed saliva (as indicated by amylase in the gastric perfusate) nor duodenogastric reflux (as indicated by gastric occurrence of bilirubin and/or duodenally infused PEG4000). Stimulation of gastric acid secretion by sham feeding during phase II-like motor activity (n = 6) induced a rapid and transient doubling of IgA output. There was no significant correlation between gastric acid secretion and gastric IgA release. CONCLUSION: Substantial amounts of IgA are released into the human stomach, most likely originating from the gastric mucosa. The up-regulation of IgA release in association with the activity front of the MMC and anticipatory to food intake suggests a neuroendocrine control of gastric mucosal immune responses.

Adult↗

The pH/PCO2 method for continuous determination of human gastric acid and bicarbonate secretion. A validation study.

BACKGROUND: The present paper describes and evaluates a methodologic approach for registration of the fast, interdigestive, motility-related changes in gastric acid and bicarbonate outputs seen in man. METHODS: The technique is based on continuous gastric luminal perfusion and measurements of pH and PCO2 in gastric effluent and concomitant intragastric/duodenal manometry. Fourteen healthy volunteers participated. RESULTS: Direct acid secretory estimations from pH recordings, corrected for hydrogen ion activity, correlated closely with values obtained by conventional titration. After intragastric infusion of bicarbonate, 96 +/- 5% of the newly measured steady-state value was registered virtually instantaneously provided that corrections for the PCO2 electrode time constant and the perfusion/aspiration time were made. In the neutral pH range (pH 5-7), practically full quantitative recovery of intragastrically infused bicarbonate was obtained. In the acid pH interval (pH 2-5) the recovery was significantly lower (53 +/- 6%; p < 0.01). With an aspirate without air admixture and during high perfusion rates (31 and 46 ml/min), full recovery of bicarbonate was obtained also at an acid pH, whereas a reduced perfusion rate (16 ml/min) significantly (p < 0.05) reduced the recovery rate. CONCLUSIONS: With the pH/PCO2 technique both acid and bicarbonate assessments have a close to on-line time resolution. Acid output is measured accurately, but the method potentially underestimates actual bicarbonate levels in the acid pH range, a combined effect of diffusion of CO2 into air bubbles in the aspirate and into the gastric mucosa from the lumen. A high gastric perfusion rate minimizes this source of error. The pH/PCO2 technique is well suited for studies of the interaction between secretion and motility in the human stomach.

Adult↗

Duodenal wall motility, mucosal net fluid and alkaline secretion in response to luminal acid: role of the vagal nerves and cholinergic transmission.

Experiments were performed on chloralose anaesthetized cats. Biliary and pancreatic secretions were diverted by separate cannulation of each duct. A 2-cm segment of the proximal duodenum was isolated between two luminally situated balloons and perfused with isotonic saline containing 14C-PEG 4000 as a non-absorbable marker. The perfusate was analysed with regard to alkalinity (back titration) and concentration of marker (liquid scintillation). Net alkalinization and net fluid transport were calculated with conventional equations. Motor activity in the duodenal wall was recorded as changes in volume of the proximal balloon. Exposing the duodenal segment of 30 mM HCl induced duodenal contractions, net fluid secretion and an increased alkaline secretion, responses which were insensitive to acute truncal vagotomy. The acid-induced increase in contraction frequency was inhibited by hexamethonium, but not by atropine. Alkaline secretion in response to luminal acid was blocked by hexamethonium and inhibited by atropine, whereas the net fluid secretion was insensitive to these compounds. It is concluded that luminal exposure to hydrochloric acid changes the duodenal functional state by mechanisms which are independent of the extrinsic neural supply. Duodenal contractions during luminal acid exposure, and the alkalinization after such acid exposure, are mediated via local neural pathways, involving a nicotinic cholinergic step and, to some degree, muscarinic transmission. The mucosal volume secretion, however, appears to be mediated by non-conventional mechanisms.

Alkalies↗

On the point of action for sympatho-adrenergic inhibition of duodenal alkaline secretion in the rat.

Experiments were performed on chloralose anaesthetized rats. A duodenal segment was decentralized by means of bilateral vagotomy and splanchnicotomy. The mucosal alkaline secretion by the segment was measured using an in situ pH-stat titration. The duodenal alkaline secretion was raised by about 100% utilizing two different secretagogues; vasoactive intestinal polypeptide (VIP) and prostaglandin E2 (PGE2). Direct splanchnic nerve stimulation (10 Hz, 5 min, bilaterally), or exogenous administration of the alpha-2-adrenoceptor agonist clonidine (15 micrograms h-1 kg-1), inhibited the secretion stimulated by PGE2, but not by VIP. The results suggest that the sympathetic nerves exert their inhibitory effect mainly on enteric secretomotor neurones.

Animals↗

Accumulation of an endogenous inhibitor of nitric oxide synthase during graded hemorrhagic shock.

Asymmetric dimethylarginine (ADMA) represents an endogenous inhibitor of nitric oxide (NO) production. The production of ADMA has been shown to increase during cellular stress, e.g., hypoxia. Furthermore, ADMA has recently been reported to accumulate in plasma during terminal renal failure as a consequence of diminished urinary excretion. Since tissue hypoxia and oliguria are both characteristics of severe hemorrhagic shock, this study was performed in order to establish whether plasma concentrations of ADMA increase during hemorrhagic shock. Six pigs were subjected to graded hemorrhage (20% and 40% of the calculated blood volume), resulting in significant (P < 0.05) reductions in blood pressure and cardiac output (from 98 +/- 4 to 36 +/- 5 mm Hg and from 3.0 +/- 0.2 to 1.4 +/- 0.2 L/min, respectively). Plasma ADMA concentrations as determined by high-performance liquid chromatography (HPLC) increased from a pre-hemorrhage value of 3.4 +/- 0.3 microM to 3.9 +/- 0.4 microM (ns) and 5.2 +/- 0.4 microM (P < 0.05), respectively. The present study demonstrates that plasma ADMA concentrations increase significantly during hemorrhagic shock. Thus, inhibition of the arginine-nitric oxide pathway as a result of ADMA accumulation, may represent an additional physiological mechanism to maintain systemic blood pressure in response to acute hypovolemia.

Amino Acid Oxidoreductases↗

Measurements of duodenal wall motility, mucosal fluid transport and alkaline secretion. Description and evaluation of a methodological approach in the anaesthetized cat.

This paper describes and evaluates a method for simultaneous recordings of duodenal motility and mucosal secretions in chloralose-anaesthetized cats. Biliary and pancreatic secretions were diverted by separate cannulation of each duct. A 2 cm segment of the proximal duodenum was isolated between two luminally situated balloons (the proximal balloon being positioned immediately distal to the pylorus). Each balloon was connected to a barostatic device maintaining a constant pressure within the balloon independent of the degree of contraction. Motor activity in the duodenal wall was recorded as changes in balloon volume. The duodenal segment was perfused at a constant rate with isotonic saline containing [14C]PEG 4000 as a non-absorbable marker. The recovered perfusate was sampled in 5 min fractions and analysed with regard to alkalinity (back titration) and concentration of marker (liquid scintillation). Net alkalinization and net fluid transport was calculated with conventional equations. The sensitivity of the analytical procedures was tested bench-side. The technique was evaluated in vivo during basal conditions and during acid exposure of the mucosa. Exposing the duodenal segment to 30 mM HCl induced a marked change in the duodenal functional state with the occurrence of a polarized duodenal motility pattern, net fluid secretion and an increased alkaline secretion.

Anesthesia↗

Does antral distension inhibit gastric acid secretion or stimulate bicarbonate secretion in 'healthy' subjects?

The effects of a 150-ml antral balloon distension on pentagastrin-stimulated gastric acid secretion and bicarbonate secretion were studied in nine healthy subjects and eight duodenal ulcer (DU) patients. The gastric secretions were simultaneously measured, using a luminal perfusion and pH/PCO2 measurements. Two of the healthy subjects and six of the DU patients were positive for Helicobacter pylori. When H. pylori-positive and -negative subjects were compared, basal gastric acid and bicarbonate outputs did not differ significantly. In H. pylori-infected subjects the bicarbonate transport increased by about 70% on pentagastrin stimulation. In the H. pylori-negative group pentagastrin had no effect on the bicarbonate secretion. Antral distension elicited a 30-35% inhibition of pentagastrin-stimulated gastric acid secretion in the group of H. pylori-negative subjects, whereas the acid secretory level remained essentially unchanged in the positive group. Bicarbonate secretion decreased transiently by the distension in the negative subjects, whereas a slight increase was observed in the infected group. We conclude that antral distension inhibits pentagastrin-stimulated gastric acid output in healthy H. pylori-negative subjects. Our results strongly suggest that the underlying mechanism is a direct inhibition of gastric parietal cell function and not an increased gastric bicarbonate secretion. Furthermore, the results indicate that this defective distension-induced acid inhibition may be correlated to H. pylori infection rather than to duodenal ulcer disease.

Adult↗

The mediation of increased duodenal alkaline secretion in response to 10 mM HCl in the anaesthetized rat. Support for the involvement of capsaicin-sensitive nerve elements.

Experiments were performed on chloralose-anaesthetized rats. Bicarbonate secretion by the duodenal mucosa was continuously recorded by use of an in situ-titration technique. Exposing the duodenal segment to 10 mM HCl over 5 min increased the bicarbonate transport by about 65%. This acid-induced secretory response was resistant to neural decentralization by means of bilateral cervical vagotomy and/or splanchnicotomy. Furthermore, in the decentralized state, serosal application of the local anaesthetic lidocaine or tetrodotoxin (TTX) lowered basal duodenal bicarbonate secretion. Despite the presence of lidocaine or TTX, exposure of the duodenal mucosa to 10 mM HCl induced a net increase in secretion with a magnitude similar to that observed in the control situation with intact nerves. A 5-min exposure period of the decentralized duodenal segment to capsaicin (1.2 mg ml-1) raised bicarbonate secretion, a response which also occurred in the presence of lidocaine (serosa). Tachyphylaxis to capsaicin blocked the secretory response to 10 mM HCl and inhibited the response to luminal prostaglandin E2 (1.5 10(-5) M) by 80%. The present results indicate that luminal exposure to 10 mM HCl activates capsaicin-sensitive primary afferents which, locally within the submucosa or epithelium, activate the bicarbonate secretion.

Animals↗

Hypovolaemia inhibits acid-induced alkaline transport in the rat duodenum via an alpha-2 adrenergic mechanism.

Acid exposure of the duodenal mucosa is a well-known stimulant of the mucosal alkaline secretion. We have previously reported that a minor blood loss inhibits this secretory increment via activation of the splanchnic nerves. In the present study the pharmacological characteristics of the splanchnic neural inhibition of the alkaline secretion were investigated. Duodenal HCO3- secretion was measured by in-situ titration in chloralose-anaesthetized rats. Exposure of the duodenal mucosa to hydrochloric acid (0.01 M, 5 min) increased the secretion by approximately 60%. A 10% decrease in blood volume simultaneously to the luminal acidification abolished the secretory increase, as previously reported. Treatment with either guanethidine or yohimbine blocked the bleeding-induced inhibition of the secretion after acid-exposure. Neither prazosin nor propranolol did prevent such hypovolaemia-induced inhibition of duodenal alkaline secretion. The present results suggest that the splanchnic neural inhibition of acid-induced duodenal HCO3- secretion is mediated via adrenergic nerve fibres and alpha-2 adrenoceptors.

Animals↗