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Local metabolic effects of dopexamine on the intestine during mesenteric hypoperfusion.
Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Surgery.
Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
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2004 (English)In: Shock, ISSN 1073-2322, Vol. 21, no 3, 241-247 p.Article in journal (Refereed) Published
Abstract [en]

This self-controlled experimental study was designed to test the hypothesis that dopexamine, a synthetic catecholamine that activates dopaminergic (DA-1) and beta2-adrenergic receptors, improves oxygenation in the jejunal mucosa during intestinal hypotension. In six normoventilated barbiturate-anesthetized pigs, controlled reductions in superior mesenteric arterial pressure (PSMA) was obtained by an adjustable clamp around the artery. Dopexamine infusions (0.5 and 1.0 were administered at a freely variable PSMA (i.e., with the perivascular clamp fully open) and at a PSMA of 50 mmHg and 30 mmHg. We continuously measured superior mesenteric venous blood flow (QMES; transit-time ultrasonic flowmetry), jejunal mucosal perfusion (laser Doppler flowmetry), and tissue oxygen tension (PO2TISSUE; microoximetry). Jejunal luminal microdialysate of lactate, pyruvate, and glucose were measured every 5 min. Measurements of mucosal PCO2 (air tonometry), together with blood sampling and end-tidal PCO2 measurements, enabled calculations of pHi and PCO2 gap. Dopexamine reduced mesenteric vascular resistance and increased QMES at a PSMA of 50 mmHg and 30 mmHg. At a PSMA of 30 mmHg, dopexamine increased mesenteric oxygen delivery but did not influence mesenteric oxygen uptake or extraction. In this situation, dopexamine had no beneficial effect on jejunal mucosal blood flow. On the contrary, dopexamine increased mesenteric net lactate production and PCO2 gap, whereas PO2TISSUE and pHi decreased. Jejunal luminal microdialysate data demonstrated an increased lactate concentration and a pattern of decreased glucose concentration and increased luminal lactate-pyruvate ratio. These negative metabolic effects of dopexamine should be taken into account in situations of low perfusion pressures.

Place, publisher, year, edition, pages
2004. Vol. 21, no 3, 241-247 p.
Keyword [en]
Adrenergic beta-Agonists/pharmacology, Animals, Blood Pressure, Catecholamines/pharmacology, Dopamine/*analogs & derivatives/*pharmacology, Female, Intestinal Mucosa/drug effects/pathology, Intestines/*drug effects, Jejunum/pathology, Laser-Doppler Flowmetry, Mesenteric Arteries/*pathology, Microdialysis, Oxygen/metabolism, Perfusion, Pressure, Receptors; Adrenergic; beta-2/metabolism, Swine, Time Factors, Ultrasonics
URN: urn:nbn:se:umu:diva-6005DOI: 10.1097/01.shk.0000111826.07309.8bPubMedID: 14770037OAI: diva2:145673
Available from: 2008-01-12 Created: 2008-01-12 Last updated: 2015-09-15Bibliographically approved
In thesis
1. Exploring Intestinal Ischemia: An experimental study
Open this publication in new window or tab >>Exploring Intestinal Ischemia: An experimental study
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background and aims: Unrecognized intestinal mucosal ischemia in severely ill patients may trigger development of multiple organ failure. Such ischemia can be evaluated by intraluminal tonometry reflecting mucosal PCO2 and intramucosal pH (pHi). The aims were to develop an apparatus for continuous saline tonometry (CST), to analyse circulatory control mechanisms during intestinal hypoperfusion and to evaluate the effect of dopexamine on intestinal circulation.

Methods: A modified standard tonometry catheter was integrated in a closed system with circulating saline. By measuring saline PCO2 in a measurement unit pHi could be calculated. This novel system was tested in vitro and in vivo. In a porcine study, CST was evaluated against standard saline tonometry, tissue oxygenation (PO2 TISSUE), jejunal mucosal perfusion (laser doppler flowmetry; LDF) and mesenteric net lactate flux during graded reductions of superior mesenteric arterial pressure (PSMA). Local control mechanisms for maintenance of intestinal oxygenation were analysed. Effects of dopexamine on the intestinal vascular bed were explored. Mucosal lactate production was assessed by microdialysis.

Results: CST measured accurate PCO2 values and changes in pHi during restricted intestinal circulation and at reperfusion. Local control mechanisms were insufficient at a PSMA of 30 mmHg, pHi was reduced to 7.10 and intestinal net lactate production was demonstrated. Absence of anaerobic intestinal metabolism was verified at PSMA ≥ 50 mmHg, pHi ≥ 7.22 and a PCO2 gap ≤ 15.8 mmHg. Dopexamine induced negative regional metabolic effects at the lowest PSMA, as expressed by decreased PO2 TISSUE and pHi, increased PCO2 gap and intestinal net lactate production.

Conclusions: CST reflected changes in pHi, induced by intestinal hypoperfusion and at reperfusion. Levels of PSMA, pHi and PCO2 gap as indicators of aerobic conditions were defined. Dopexamine induced a decrease of PO2 TISSUE and pHi as well as an increase in lactate flux at the lowest PSMA level.

Place, publisher, year, edition, pages
Umeå: Kirurgisk och perioperativ vetenskap, 2005. 59 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 938
Surgery, gastrointestinal tonometry, continuous, pig, pHi, intestinal ischemia, intestinal vascular bed, lactate, tissue oxygen tension, microdialysis, dopexamine, Kirurgi
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Research subject
urn:nbn:se:umu:diva-461 (URN)91-7305-788-6 (ISBN)
Public defence
2005-03-19, B, Tandläkarhögskolan, 9tr, Norrlands Universitetssjukhus, Umeå, 10:00 (English)
Available from: 2005-02-24 Created: 2005-02-24 Last updated: 2009-11-13Bibliographically approved

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