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Intestinal effects of lung recruitment maneuvers
Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences.
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background and aims: Lung recruitment maneuvers (brief episodes of high airway pressure) are a modern treatment alternative to achieve open lung conditions under mechanical ventilation of patients with acute lung injury. It is well known that positive pressure ventilation with high airway pressures cause negative circulatory effects, and that the effects on regional vascular beds can be even more pronounced than the systemic effects. Hypoperfusion of the mesenteric vascular bed can lead to tissue ischemia and local inflammation. This intestinal inflammation has been associated with subsequent development of multiple organ dysfunction syndrome, a syndrome that still carries a high mortality and is a leading cause of death for intensive care patients. The aim of this thesis was therefore to investigate whether lung recruitment maneuvers would cause negative effects on mesenteric circulation, oxygenation or metabolism.

Methods and results: In an initial study on ten patients with acute lung injury, we could demonstrate a trend towards a decreased gastric mucosal perfusion during three repeated lung recruitment maneuvers. To more closely examine this finding, we set up an oleic acid lung injury model in pigs, and in our second study we established that this model was devoid of inherent intestinal effects and was adequate for subsequent studies of intestinal effects of lung recrutiment maneuvers. In the acute lung injury model, we also tested the effect of an infusion of a vasodilating agent concurrent with the recruitment maneuvers, the hypothesis being that a vasodilating agent would prevent intestinal vasoconstriction and hypoperfusion. We could show that three repeated lung recruitment maneuvers induced short term negative effects on mesenteric oxygenation and metabolism, but that these findings were transient and short lasting. Further, the effects of prostacyclin were minor and opposing. These findings of relative little impact on the intestines of lung recruitment maneuvers, lead us to investigate the hypothesis that repeated recruitment maneuvers maybe could elicite a protective intestinal preconditioning response, a phenomenon previously described both in the rat and in the dog. However, in our fourth study, using both classical ischemic preconditioning with brief periods of intestinal ischemia or repeated lung recrutiment maneuvers, we could not demonstrate the phenomenon of intestinal preconditioning in the pig.

Conclusions: We conclude, that from a mesenteric point of view, lung recruitment maneuvers are safe, and only induce transient and short lasting negative effects. We also conclude that the cause of the minor effects of lung recruitment maneuvers is not dependent on intestinal preconditioning.

Place, publisher, year, edition, pages
Umeå: Kirurgisk och perioperativ vetenskap , 2007. , 92 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1083
Keyword [en]
acute lung injury, oleic acid lung injury, ischemia, reperfusion injury, swine, mechanical ventilation, lung recruitment, splanchnic circulation, laser Doppler flowmetry, tissue oxygen tension, microdialysis, lactate, glycerol
National Category
Anesthesiology and Intensive Care
Research subject
Lung Medicine
Identifiers
URN: urn:nbn:se:umu:diva-981ISBN: 978-91-7264-254-6 (print)OAI: oai:DiVA.org:umu-981DiVA: diva2:145283
Public defence
2007-02-23, Sal B, 9 tr, Tandläkarhögskolan, 90185, Umeå, 13:00 (English)
Opponent
Supervisors
Available from: 2007-01-29 Created: 2007-01-29 Last updated: 2009-05-15Bibliographically approved
List of papers
1. Do lung recruitment maneuvers decrease gastric mucosal perfusion?
Open this publication in new window or tab >>Do lung recruitment maneuvers decrease gastric mucosal perfusion?
2003 (English)In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 29, no 8, 1314-1321 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:umu:diva-5682 (URN)10.1007/s00134-003-1830-z (DOI)
Available from: 2007-01-29 Created: 2007-01-29 Last updated: 2017-12-14Bibliographically approved
2. Intestinal circulation, oxygenation and metabolism is not affected by oleic acid lung injury.
Open this publication in new window or tab >>Intestinal circulation, oxygenation and metabolism is not affected by oleic acid lung injury.
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2005 (English)In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 25, no 6, 357-363 p.Article in journal (Refereed) Published
Abstract [en]

This study was performed to establish a platform for further studies on effects of ventilatory treatment modalities on the intestines during mechanical ventilation of acute lung injury (ALI). We tested the hypotheses that oleic acid (OA) infusion causes changes in intestinal circulation, oxygenation and metabolism, and that OA is distributed to tissues outside the lung. This was performed as an experimental, prospective and controlled study in an university animal research laboratory. Thirteen juvenile anaesthetized pigs were used in the main study, where seven were given an intravenous infusion of 0.1 ml kg(-1) OA and six served as control (surgery only). In a separate study, four animals were given an intravenous infusion of 0.1 ml kg(-1) (3)H-labelled OA. We measured systemic and mesenteric (portal venous blood flow, jejunal mucosal perfusion) haemodynamic parameters, mesenteric oxygenation (jejunal tissue oxygen tension) and systemic cytokines (tumour necrosis factor-alpha and interleukin-6). We calculated mesenteric lactate flux and mesenteric oxygen delivery, uptake and extraction ratio. In the animals given 3H-OA, we measured 3H-OA in different tissues (lungs, heart, liver, kidney, stomach, jejunum, colon and arterial blood). We found that OA given intravenously is distributed in small amounts to the intestines. This intestinal exposure to OA does not cause intestinal injury when evaluating mesenteric blood flow, metabolism or oxygenation. OA infusion induced a moderate increase in mean pulmonary arterial pressure and a decrease in PaO2/Fraction inspired O2 (P/F) ratio, giving evidence of severe lung injury. Consequently, the OA lung injury model is suitable for studies on intestinal effects of ventilatory treatment modalities during mechanical ventilation of ALI.

Keyword
Animals, Disease Models; Animal, Female, Injections; Intravenous, Intestines/*blood supply/drug effects/*physiopathology, Metabolic Clearance Rate, Oleic Acid/*administration & dosage/*pharmacokinetics, Oxygen/*metabolism, Respiratory Distress Syndrome; Adult/chemically induced/*physiopathology, Swine, Tissue Distribution
Identifiers
urn:nbn:se:umu:diva-6033 (URN)10.1111/j.1475-097X.2005.00640.x (DOI)16268988 (PubMedID)
Available from: 2007-12-18 Created: 2007-12-18 Last updated: 2017-12-14Bibliographically approved
3. Negative mesenteric effects of lung recruitment maneuvers in oleic acid lung injury are transient and short lasting.
Open this publication in new window or tab >>Negative mesenteric effects of lung recruitment maneuvers in oleic acid lung injury are transient and short lasting.
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2007 (English)In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 35, no 1, 230-238 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To test the hypothesis that repeated recruitment maneuvers (RMs) have sustained negative effects on mesenteric circulation, metabolism, and oxygenation 60 mins after RMs in pigs with oleic acid lung injury. Further, we aimed to test the hypothesis that an infusion of prostacyclin (PC) at 33 ng.kg.min would attenuate such possible negative mesenteric effects. DESIGN: Randomized, experimental, controlled study. SETTING: University hospital animal laboratory. SUBJECTS: A total of 31 anesthetized, fluid-resuscitated pigs with oleic acid lung injury. INTERVENTIONS: Animals were randomized to one of the following four groups: a control group (n = 7) that received no intervention, recruitment group (n = 8) that underwent the RM sequence, a prostacyclin group (n = 8) that received an infusion of PC, and a recruitment-prostacyclin group (n = 8) that received an infusion of PC and concomitant RM sequence. MEASUREMENTS AND MAIN RESULTS: We measured systemic and mesenteric hemodynamic variables, jejunal mucosal perfusion, mesenteric lactate flux, jejunal tissue oxygen tension, and mesenteric oxygen delivery, uptake, and extraction ratio. Five minutes after RMs, mesenteric oxygen extraction ratio and mesenteric lactate flux were more prominently increased in the recruitment group, giving evidence of worsened mesenteric conditions after RMs. These signs of worsened conditions were further supported by more decreased jejunal tissue oxygen tension and portal vein oxygen saturation in the recruitment group. PC preserved mesenteric oxygenation, as indicated by less of a decrease in portal vein oxygen saturation at the time corresponding to 5 mins after RM and less of a decrease in mesenteric oxygen delivery at the time corresponding to 15 mins after RM. PC preserved mesenteric oxygenation as indicated by less of a decrease in portal vein oxygen saturation at 5 mins after RM and an attenuated increase in mesenteric oxygen extraction ratio at 5 mins after RM. There was a trend toward worsened jejunal mucosal perfusion, although not significant. CONCLUSIONS: In an oleic acid lung injury model, three repeated RMs did not improve systemic oxygenation or lung mechanics. Negative effects on mesenteric oxygenation and metabolism were transient and short lasting. The intestinal effects of PC during RMs were minor and opposing, showing preserved oxygenation but a trend toward worsened mucosal perfusion.

Keyword
Animals, Antihypertensive Agents/pharmacology/*therapeutic use, Blood Flow Velocity/drug effects, Blood Gas Analysis, Blood Pressure/drug effects, Cardiac Output/drug effects, Disease Models; Animal, Drug Evaluation; Preclinical, Epoprostenol/pharmacology/*therapeutic use, Female, Infusions; Intravenous, Intestinal Mucosa/blood supply/drug effects/metabolism, Jejunum/blood supply/drug effects/metabolism, Lactic Acid/metabolism, Lung Volume Measurements, Oleic Acid, Oxygen Consumption/drug effects, Random Allocation, Respiration; Artificial/adverse effects/methods, Respiratory Distress Syndrome; Adult/chemically induced/metabolism/physiopathology/*therapy, Respiratory Mechanics/drug effects, Splanchnic Circulation/drug effects, Swine, Time Factors
Identifiers
urn:nbn:se:umu:diva-7123 (URN)17110875 (PubMedID)
Available from: 2008-01-04 Created: 2008-01-04 Last updated: 2017-12-14Bibliographically approved
4. Evaluation of intestinal preconditioning in a porcine model using classic ischemic preconditioning or lung recruitment maneuvers.
Open this publication in new window or tab >>Evaluation of intestinal preconditioning in a porcine model using classic ischemic preconditioning or lung recruitment maneuvers.
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2008 (English)In: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 21, no 1, 98-103 p.Article in journal (Refereed) Published
Abstract [en]

To test the hypotheses that repeated brief intestinal ischemic insults would elicit an intestinal preconditioning response to a subsequent intestinal I/R injury and that a similar response would be elicited by repeated lung recruitment maneuvers (RMs). Randomized experimental controlled animal study. University hospital animal laboratory. Eighteen anesthetized pigs. Animals were randomized to one of three groups, with six animals in each group. Control group 75-min superior mesenteric artery (SMA) occlusion followed by 60-min reperfusion. Ischemic preconditioning group, three 5-min-long SMA occlusions preceding 75-min SMA occlusion and 60-min reperfusion. Recruitment maneuver (RM) group, three 2-min-long RMs preceding 75-min SMA occlusion and 60-min reperfusion. We measured systemic and mesenteric hemodynamic parameters, jejunal mucosal perfusion, net mesenteric lactate flux, jejunal tissue oxygen tension, and mesenteric oxygenation. Every 15 min, jejunal microdialysate samples were collected and analyzed for glucose, lactate, and glycerol. Jejunal tissue samples were collected postmortem. After occlusion of SMA, regional parameters in all groups indicated abolished perfusion and gradually increasing intraluminal microdialysate lactate and glycerol levels. At reperfusion, regional parameters indicated mesenteric hyperperfusion, whereas microdialysis markers of mucosal anaerobic metabolism and cell injury decreased, although not reaching baseline. Histological examination revealed severe mucosal injury in all groups. There were no significant differences between groups in the observed parameters. No protective preconditioning response could be observed when performing repeated brief intestinal ischemic insults or repeated lung RMs before an intestinal I/R injury.

Keyword
Animals, Blood Pressure/physiology, Epinephrine/pharmacology, Isoflurane/pharmacology, Myocardial Contraction/*drug effects/physiology, Myocardial Revascularization/methods, Stroke Volume, Swine, Vasoconstrictor Agents/pharmacology
Identifiers
urn:nbn:se:umu:diva-7125 (URN)18157068 (PubMedID)
Available from: 2008-01-04 Created: 2008-01-04 Last updated: 2017-12-14Bibliographically approved

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