umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Carbon monoxide in biological systems: An experimental and clinical study
Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences.
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.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1134
Keyword [en]
Carbon monoxide, physiological effects, systemic inflammation, analytical method, blood, exhaled air, pharmacokinetics, cigarette smoking, blood donation, cytokines
National Category
Anesthesiology and Intensive Care
Identifiers
URN: urn:nbn:se:umu:diva-1427ISBN: 978-91-7264-431-1 (print)OAI: oai:DiVA.org:umu-1427DiVA: diva2:141018
Public defence
2007-11-30, Sal B, 9tr, Tandläkarhögskolan, Umeå Universitet, Umeå, 13:00 (English)
Opponent
Supervisors
Available from: 2007-11-09 Created: 2007-11-09 Last updated: 2009-09-25Bibliographically approved
List of papers
1. Rapid and sensitive method for the analysis of carbon monoxide in blood using gas chromatography with flame ionisation detection
Open this publication in new window or tab >>Rapid and sensitive method for the analysis of carbon monoxide in blood using gas chromatography with flame ionisation detection
2002 (English)In: Journal of chromatography. B, ISSN 1570-0232, E-ISSN 1873-376X, Vol. 766, no 1, 115-121 p.Article in journal (Refereed) Published
Abstract [en]

In order to measure changes in physiological CO concentrations in blood with good accuracy, a method was developed using gas chromatography with flame ionisation detection (250 degrees C). A nickel catalyst system was fitted to convert CO to methane at 375 degrees C after separation with a molecular sieve column at 35 degrees C. Helium was used as carrier at 30 ml/min. Porcine or human blood (400 microl) was sampled in gastight tubes and treated with sulfuric acid and saponin (800 microl). Accuracy was 1.4% and 1.5% (RSD), respectively. Precision was 2.8% (porcine blood). Limit of detection was 0.01 nmol/ml gas and limit of quantification 12 nmol/ml blood. Calibration was made in the interval 12-514 nmol/ml blood (corresponding to 0.1-6% COHb). Samples were stable for at least a month at +4 degrees C. This paper describes a method with high sensitivity and good accuracy, suitable for analysis of low CO concentrations.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-2753 (URN)10.1016/S0378-4347(01)00460-1 (DOI)11820286 (PubMedID)
Available from: 2007-11-09 Created: 2007-11-09 Last updated: 2017-12-14Bibliographically approved
2. Circulatory effects and kinetics following acute administration of carbon monoxide in a porcine model.
Open this publication in new window or tab >>Circulatory effects and kinetics following acute administration of carbon monoxide in a porcine model.
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).

Keyword
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
Identifiers
urn:nbn:se:umu:diva-6804 (URN)10.1016/j.lfs.2003.12.030 (DOI)15207651 (PubMedID)
Available from: 2008-01-12 Created: 2008-01-12 Last updated: 2017-12-14Bibliographically approved
3. Does carbon monoxide treatment alter cytokine levels after endotoxin infusion in pigs?: A randomized controlled study
Open this publication in new window or tab >>Does carbon monoxide treatment alter cytokine levels after endotoxin infusion in pigs?: A randomized controlled study
Show others...
2008 (English)In: Journal of Inflammation, ISSN 1476-9255, Vol. 5, 13.- p.Article in journal (Refereed) Published
Abstract [en]

ABSTRACT: BACKGROUND: Carbon monoxide (CO) has recently been suggested to have anti-inflammatory properties, but data seem to be contradictory and species-specific. Thus, in studies on macrophages and mice, pretreatment with CO attenuated the inflammatory response after endotoxin exposure. On the other hand, human studies showed no effect of CO on the inflammatory response. Anti-inflammatory efficacy of CO has been shown at concentrations above 10% carboxyhaemoglobin. This study was undertaken to elucidate the possible anti-inflammatory effects of CO at lower CO concentrations. METHODS: Effects of CO administration on cytokine (TNF-alpha, IL-6, IL-1beta and IL-10) release were investigated in a porcine model in which a systemic inflammatory response syndrome was induced by endotoxin infusion. Endotoxin was infused in 20 anaesthetized and normoventilated pigs. Ten animals were targeted with inhaled CO to maintain 5% COHb, and 10 animals were controls. RESULTS: In the control group, mean pulmonary artery pressure increased from a baseline value of 17 mmHg (mean, n = 10) to 42 mmHg (mean, n = 10) following 1 hour of endotoxin infusion. Similar mean pulmonary artery pressure values were found in animals exposed to carbon monoxide. Plasma levels of all of the measured cytokines increased in response to the endotoxin infusion. The largest increase was observed in TNF-alpha, which peaked after 1.5 hours at 9398 pg/ml in the control group and at 13395 pg/ml in the carbon monoxide-exposed group. A similar peak was found for IL-10 while the IL-6 concentration was maximal after 2.5 hours. IL-1beta concentrations increased continuously during the experiment. There were no significant differences between carbon monoxide-exposed animals and controls in any of the measured cytokines. CONCLUSION: Our conclusion is that 5% COHb does not modify the cytokine response following endotoxin infusion in pigs.

Identifiers
urn:nbn:se:umu:diva-2755 (URN)10.1186/1476-9255-5-13 (DOI)18687112 (PubMedID)
Available from: 2007-11-09 Created: 2007-11-09 Last updated: 2015-09-15Bibliographically approved
4. Carbon monoxide concentration in donated blood: relation to cigarette smoking and other sources
Open this publication in new window or tab >>Carbon monoxide concentration in donated blood: relation to cigarette smoking and other sources
Show others...
2009 (English)In: Transfusion, ISSN 0041-1132, E-ISSN 1537-2995, Vol. 49, no 2, 347-353 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Carbon monoxide (CO) is normally present in the human body due to endogenous production of CO. CO can also be inhaled by exposure to external sources such as cigarette smoke, car exhaust, and fire. The purpose of this study was to investigate CO concentrations in blood from 410 blood donors at the blood center in Umea, Sweden. To further evaluate the effects of cigarette smoking on CO concentrations, the elimination time for CO was examined in six volunteer smokers after a smoked cigarette. STUDY DESIGN AND METHODS: Blood samples from whole blood donors were obtained during the blood center's routine operation. In connection with blood donations, demographic and behavioral data were collected from the donors. The CO concentration was determined using gas chromatography. RESULTS: The majority of blood donors had approximately the same CO concentration (mean, 84.5 micromol/L). In 6 percent of the samples, the concentrations were higher than 130 micromol per L. The highest CO concentration was 561 micromol per L. The main source for these high CO concentrations appeared to be cigarette smoking. In the volunteer smokers, the elimination time after a smoked cigarette varied significantly, with elimination half-lives from 4.7 to 8.4 hours. CONCLUSION: These results show that blood bank red blood cell bags may have CO concentrations above the physiologic level. The time interval between cigarette smoking and blood donation seems to be a particularly important factor for elevated CO concentrations.

Identifiers
urn:nbn:se:umu:diva-2756 (URN)10.1111/j.1537-2995.2008.01951.x (DOI)18980621 (PubMedID)
Available from: 2007-11-09 Created: 2007-11-09 Last updated: 2017-12-14Bibliographically approved

Open Access in DiVA

fulltext(575 kB)1163 downloads
File information
File name FULLTEXT01.pdfFile size 575 kBChecksum SHA-1
cc0eb99a6bfd9dbcfb2c8b517d83a60af8d386de86beebcd1f1c6a852e25253c3369fde3
Type fulltextMimetype application/pdf

By organisation
Surgical and Perioperative Sciences
Anesthesiology and Intensive Care

Search outside of DiVA

GoogleGoogle Scholar
Total: 1163 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 524 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf