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Exploring Intestinal Ischemia: An experimental study
Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences.
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.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 938
Keyword [en]
Surgery, gastrointestinal tonometry, continuous, pig, pHi, intestinal ischemia, intestinal vascular bed, lactate, tissue oxygen tension, microdialysis, dopexamine
Keyword [sv]
Kirurgi
National Category
Surgery
Research subject
Surgery
Identifiers
URN: urn:nbn:se:umu:diva-461ISBN: 91-7305-788-6 (print)OAI: oai:DiVA.org:umu-461DiVA: diva2:143507
Public defence
2005-03-19, B, Tandläkarhögskolan, 9tr, Norrlands Universitetssjukhus, Umeå, 10:00 (English)
Opponent
Supervisors
Available from: 2005-02-24 Created: 2005-02-24 Last updated: 2009-11-13Bibliographically approved
List of papers
1. A new method for continuous tonometric pCO2 measurement - in vitro studies.
Open this publication in new window or tab >>A new method for continuous tonometric pCO2 measurement - in vitro studies.
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1999 (English)In: Physiological Measurement, ISSN 0967-3334, E-ISSN 1361-6579, Vol. 20, no 2, 129-136 p.Article in journal (Refereed) Published
Abstract [en]

The available methods for tonometric pCO2 measurement only provide the possibility of performing intermittent registrations. A new method allowing continuous tonometric pCO2 measurement has been developed and tested in an in vitro model. A standard tonometer for intestinal pCO2 measurement was modified to allow continuous perfusion of the balloon with physiological saline solution in a closed system. The pCO2 in the system was determined in a specially constructed measurement chamber with a TCM20 percutaneous pCO2 monitor. In this in vitro model the tonometer balloon was placed in a saline bath with a constant pCO2 concentration and the measurements from the closed circulating system were compared with those obtained from a standard tonometer placed in the same bath. In 8 and 24 h experiments the circulating system measured the pCO2 value as accurately and reliably as traditional tonometry. This study indicates that the new method makes continuous monitoring of pCO2 possible.

Keyword
tonometry, continuous, pCO2 measurement
Identifiers
urn:nbn:se:umu:diva-4409 (URN)10.1088/0967-3334/20/2/002 (DOI)10390015 (PubMedID)
Available from: 2005-02-24 Created: 2005-02-24 Last updated: 2017-12-14Bibliographically approved
2. Validation of a novel method for continuous saline tonometry in a procine model.
Open this publication in new window or tab >>Validation of a novel method for continuous saline tonometry in a procine model.
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2001 (English)In: Physiological Measurement, ISSN 0967-3334, E-ISSN 1361-6579, Vol. 22, no 3, 453-460 p.Article in journal (Refereed) Published
Abstract [en]

Only intermittent and semi-continuous tonometric measurement of gastric and intestinal pHi is possible with the equipment available today. Earlier we developed a system for continuous saline tonometry and tested it in vitro. To assess the in vivo reliability of this method for continuous gastrointestinal saline tonometry, a standard tonometer for measurement of intestinal pCO2 and corresponding pHi was modified to allow continuous perfusion of physiological saline in a closed system and tested in a porcine model. In 11 anaesthetized and haemodynamically stable pigs, two continuous tonometry balloons were inserted into the distal small bowel, and a standard tonometry balloon was used as reference. To test long-term function of the continuous tonometers the research protocol lasted for eight hours. The two continuous saline tonometers performed well, and after an equilibration time of three hours the mean pHi values were stable between 7.35 and 7.43 and between 7.32 and 7.39 respectively. The standard tonometer measured stable pHi values. These preliminary studies indicate that continuous saline tonometry performs well over eight hours with a small bias and a good precision.

Keyword
gastrointestinal tonometry, continuous, porcine model
Identifiers
urn:nbn:se:umu:diva-4410 (URN)10.1088/0967-3334/22/3/304 (DOI)11556666 (PubMedID)
Available from: 2005-02-24 Created: 2005-02-24 Last updated: 2017-12-14Bibliographically approved
3. Intestinal pHi studied with continuous saline tonometry during ischaemia and reperfusion in the pig.
Open this publication in new window or tab >>Intestinal pHi studied with continuous saline tonometry during ischaemia and reperfusion in the pig.
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2002 (English)In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 24, no 2, 150-155 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To evaluate continuous saline tonometry for detection of progressive intestinal ischaemia and reperfusion in a porcine model. DESIGN: In eight anaesthetised pigs, small bowel mucosal pCO2 was recorded by means of two identical equipments for continuous saline tonometry and a standard tonometry balloon during ischaemia and reperfusion. RESULTS: Both systems of saline tonometry functioned stably during the four hour protocol ischaemia, although not significant until after 45 min for one of the tonometers. CONCLUSION: The equipment for continuous saline tonometry has a good reactivity, an accuracy comparable with standard tonometry.

Keyword
Continuous tonometry, Induced intestinal ischaemia, pHi, Pig, Saline tonometry
Identifiers
urn:nbn:se:umu:diva-4411 (URN)10.1053/ejvs.2002.1679 (DOI)12389238 (PubMedID)
Available from: 2005-02-24 Created: 2005-02-24 Last updated: 2017-12-14Bibliographically approved
4. Assessment of graded intestinal hypoperfusion and reperfusion using continuous saline tonometry in a porcine model.
Open this publication in new window or tab >>Assessment of graded intestinal hypoperfusion and reperfusion using continuous saline tonometry in a porcine model.
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2004 (English)In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 28, no 1, 79-88 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To evaluate effects of graded intestinal hypoperfusion and reperfusion on intestinal metabolic parameters as assessed by a modified continuous saline tonometry technique. MATERIALS: Twelve barbiturate-anaesthetized female pigs. METHODS: Measurements were performed prior to and during three predefined levels of superior mesenteric mean arterial blood pressure (P(SMA) 70, 50 and 30 mmHg, respectively, each 80 min long), obtained by an adjustable clamp around the origin of the superior mesenteric artery, and during reperfusion. We continuously measured jejunal mucosal perfusion (laser Doppler flowmetry), jejunal tissue oxygen tension (PO(2TISSUE); microoximetry) and intramucosal PCO(2) (continuous saline tonometry) and calculated net intestinal lactate production, mesenteric oxygenation, PCO(2) gap (jejunal mucosal PCO(2)-arterial PCO(2)) and pHi. RESULTS: At P(SMA) 70 and 50 mmHg mesenteric oxygen uptake and net lactate production remained unaltered, in spite of decreased oxygen delivery. At these P(SMA) levels PCO(2) gap increased, while pHi and PO(2TISSUE) decreased. At P(SMA) 30 mmHg pronounced increases in PCO(2) gap and mesenteric net lactate production as well as marked decreases in PO(2TISSUE) and pHi were demonstrated. Data indicate absence of anaerobic conditions at an intestinal perfusion pressure (IPP)> or =41 mmHg, a pHi> or =7.22 or PCO(2) gap< or =15.8 mmHg. CONCLUSIONS: Continuous saline tonometry detected intestinal ischemia as induced by graded reductions in IPP. A threshold could be defined above which intestinal ischemia does not occur.

Keyword
Animals, Blood Pressure/physiology, Cardiac Output/physiology, Female, Heart Rate/physiology, Intestines/blood supply/*metabolism, Manometry, Mesenteric Artery; Superior/metabolism, Models; Animal, Models; Cardiovascular, Oxygen Consumption/physiology, Regional Blood Flow/physiology, Reperfusion, Severity of Illness Index, Sodium Chloride/*pharmacology, Swine, Vascular Resistance/physiology
Identifiers
urn:nbn:se:umu:diva-6007 (URN)10.1016/j.ejvs.2004.02.009 (DOI)15177236 (PubMedID)
Available from: 2007-12-18 Created: 2007-12-18 Last updated: 2017-12-14Bibliographically approved
5. Local metabolic effects of dopexamine on the intestine during mesenteric hypoperfusion.
Open this publication in new window or tab >>Local metabolic effects of dopexamine on the intestine during mesenteric hypoperfusion.
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2004 (English)In: Shock, ISSN 1073-2322, E-ISSN 1540-0514, 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 microg.kg(-1).min(-1)) 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.

Keyword
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
Identifiers
urn:nbn:se:umu:diva-6005 (URN)10.1097/01.shk.0000111826.07309.8b (DOI)14770037 (PubMedID)
Available from: 2008-01-12 Created: 2008-01-12 Last updated: 2017-12-14Bibliographically approved

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Output format
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