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Circulatory effects and kinetics following acute administration of carbon monoxide in a porcine model.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
2004 (English)In: Life Sciences, ISSN 0024-3205, E-ISSN 1879-0631, Vol. 75, no 9, 1029-1039 p.Article in journal (Refereed) Published
Abstract [en]

Carbon monoxide is produced in the endothelial cells and has possible vasodilator activity through three different pathways. The aim of this study was to demonstrate circulatory effects after administration of saturated carbon monoxide blood and to describe the pharmacokinetics of carbon monoxide. Six pigs were anesthetized and 150 ml blood was removed. This blood was bubbled with carbon monoxide until the carboxyhemoglobin (COHb) levels were 90-99%. A specific amount of this blood was then injected back to the animal. At predetermined times; arterial and mixed venous blood was drawn and analyzed for carbon monoxide. Systemic and pulmonary vascular resistance index (SVRi and PVRi) were measured and exhaled air was sampled and measured for carbon monoxide. Blood samples were gathered over 300 minutes along with measurements of invasive pressures, heart rate, cardiac output, oxygen saturation (SpO2), Hb, temperature and blood gases. We conclude that this type of exposure to carbon monoxide appears to have little or no effect on general vasomotor tone and, after correcting for basal levels of carbon monoxide, elimination occurs through the lungs as predicted by a single compartment model. The half-life of carbon monoxide was determined to be 60.5 minutes (SEM 4.7).

Place, publisher, year, edition, pages
2004. Vol. 75, no 9, 1029-1039 p.
Keyword [en]
Animals, Blood Gas Analysis, Body Temperature/drug effects, Carbon Monoxide/blood/*pharmacokinetics/*pharmacology, Carbon Monoxide Poisoning/*blood/*physiopathology, Cardiac Output/drug effects, Chromium Radioisotopes/blood, Disease Models; Animal, Dose-Response Relationship; Drug, Female, Heart Rate/drug effects, Hemoglobins/drug effects, Oxygen/blood, Sus scrofa, Time Factors, Vascular Resistance/drug effects/physiology
URN: urn:nbn:se:umu:diva-6804DOI: 10.1016/j.lfs.2003.12.030PubMedID: 15207651OAI: diva2:146474
Available from: 2008-01-12 Created: 2008-01-12 Last updated: 2010-06-08Bibliographically approved
In thesis
1. Carbon monoxide in biological systems: An experimental and clinical study
Open this publication in new window or tab >>Carbon monoxide in biological systems: An experimental and clinical study
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Carbon monoxide (CO) is a toxic gas, but it is also produced endogenously when haem is degraded. When produced in vivo, CO is believed to have positive biological effects. For example it activates the production of cyclic guanosine mono-phosphate and causes vasodilatation. CO is also believed to have anti-inflammatory properties by binding to Mitogen activated protein (MAP) kinase. Several studies in cells, mice and rats support this opinion regarding both the circulatory as well as the anti-inflammatory properties. However, studies in larger animals regarding circulatory effects have demonstrated contradictory results. The only study in humans regarding anti-inflammatory properties of CO could not demonstrate such effects.

Methods: This thesis consists of four different models. In paper I a method for analysis of CO in blood was developed using gas chromatography. In paper II a porcine model was used to investigate the elimination time for CO. The pigs in paper II had a high concentration of CO administered via blood, and CO concentrations were followed over time and kinetically parameters calculated. Circulatory parameters were also measured to evaluate if there were any circulatory changes after CO administration. In paper III CO´s anti-inflammatory properties were investigated in an endotoxin-induced systemic inflammatory model in pigs. Paper III was a randomized study where one group inhaled CO and the other group served as controls. Plasma cytokine concentrations were measured and followed over time as an indication of the inflammatory state. In paper IV, CO concentrations in blood from blood donors at the Blood Centre in Umeå were investigated. The blood donors also completed a questionnaire about age, smoking history and other possible sources for exogenous contamination of CO in the blood.

Results and conclusions: In paper I we developed a method suitable for analysis of low concentrations of CO in blood. The half-life of CO at levels of 250 µM in pigs was found to be 60 minutes. CO did not show anti-inflammatory effects after an endotoxin-induced systemic inflammation in pigs. In banked blood CO was present at concentrations up to six times higher than normal concentrations. This could be a risk when transfusing such blood to susceptible patients.

Place, publisher, year, edition, pages
Umeå: Kirurgisk och perioperativ vetenskap, 2007. 42 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1134
Carbon monoxide, physiological effects, systemic inflammation, analytical method, blood, exhaled air, pharmacokinetics, cigarette smoking, blood donation, cytokines
National Category
Anesthesiology and Intensive Care
urn:nbn:se:umu:diva-1427 (URN)978-91-7264-431-1 (ISBN)
Public defence
2007-11-30, Sal B, 9tr, Tandläkarhögskolan, Umeå Universitet, Umeå, 13:00 (English)
Available from: 2007-11-09 Created: 2007-11-09 Last updated: 2009-09-25Bibliographically approved

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