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- Snygg, Johan, 1963, et al.
(författare)
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Intestinal nitric oxide output during reduced mucosal blood flow in healthy volunteers.
- 2003
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Ingår i: Critical care medicine. - 0090-3493. ; 31:8, s. 2198-204
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Nitric oxide regulates epithelial permeability and other properties of the intestinal mucosal barrier. It previously has been shown in animals that intestinal mucosal nitric oxide production is impaired during gut hypoperfusion. The study was performed to confirm the presence of intestinal mucosal nitric oxide production in humans and to investigate the effect of gut hypoperfusion due to moderate arterial hypotension on intestinal nitric oxide concentrations. DESIGN: Open study where each subject served as his own control. SETTING: Clinical research laboratory. SUBJECTS: Nine healthy volunteers were intubated with a nasogastrointestinal tube for recordings in the distal duodenum. Intestinal nitric oxide output and motility were assessed by tonometry and manometry, respectively. Laser Doppler flowmetry and plasma angiotensin II concentration were used to investigate mucosal perfusion and a vasoregulatory response. INTERVENTIONS: Moderate hypotension was induced with lower body negative pressure over 1 hr. MEASUREMENTS AND MAIN RESULTS: Intestinal nitric oxide production varied in parallel with the migrating motor complex. Low values were obtained during phase I and peak values during phase III. Lower body negative pressure was initiated at a well-defined point in the migrating motor complex cycle. It was followed by a 40 +/- 6% reduction of laser Doppler flow signal, a 778 +/- 138% increase in angiotensin II, and a reduction in intestinal mucosal nitric oxide production by 48 +/- 8%. After lower body negative pressure, laser Doppler signal and angiotensin II concentrations returned to baseline levels within 1 hr, whereas intestinal nitric oxide output remained decreased. CONCLUSIONS: Intestinal tonometry in humans exhibits a considerable mucosal nitric oxide formation that varies in relation to intestinal motility. Intestinal nitric oxide production is depressed during conditions with lowered mucosal blood perfusion.
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| 2. |
- Snygg, Johan, 1963
(författare)
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Nitric oxide production by the intestinal mucosa during hypoperfusion
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present thesis is based on the concept that gastrointestinal blood hypoperfusion is a common phenomenon associated with critical illness. Furthermore, the development of the multiple organ dysfunction syndrome (MODS) is proposed to be initiated by gastrointestinal mucosal barrier dysfunction, allowing intestinal luminal contents to penetrate into the tissue and activate a systemic inflammatory response. As nitric oxide (NO) influences several aspects of the barrier properties, it was considered of interest to elucidate intestinal NO formation during conditions with splanchnic blood hypoperfusion. The general aims of the investigations were to develop a technique for NO measurement in the gut, define the NO source(s) detected by the technique and relate the NO synthesis to conditions typical of critical illness.Experiments were performed on anaesthetised pigs. Isoforms of nitric oxide synthase (NOS) were located in the gut wall using immunohistochemistry. The pigs were instrumented to allow for recordings of global hemodynamics, mesenteric blood perfusion and blood sampling to calculate systemic and regional oxygen-kinetics. Gut mucosal blood perfusion was recorded by use of laser Doppler flowmetry. A tonometric approach was developed for the assessment of intestinal NO-formation and the technique was evaluated bench-side and in-situ. Gut blood hypoperfusion was induced by challenging cardiac performance using graded haemorrhage, cardiac tamponade or live E. coli-sepsis. Confirmatory studies were performed in healthy volunteers where hypovolemia was mimicked by lower body negative pressure. The results showed that luminal NO tonometry is an accurate and rather easily handled technique that reflects enzymatic NO formation by the intestinal mucosal surface epithelium. Plasma level of the endogenous NOS-inhibitor asymmetric di-methylarginine (ADMA) increases and the mucosal NO decreases during severe circulatory stress induced by hypovolaemia or cardiac tamponade. Mucosal hypoperfusion and dysoxia, rather than lack of the substrate L-Arginine or the increased concentration of ADMA, explain the decreased NO signal following circulatory stress. Sepsis is associated with maintained intestinal NO formation despite a concomitant mesenteric hypoperfusion. Intestinal NO formation in man varies in relation with the interdigestive motility pattern. LBNP-induced hypotension in man is associated with markedly decreased mucosal perfusion and decreased mucosal NO formation.
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