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Vascular effects of hyperoxaemia and its mechanisms in man
Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Most cells in the human body cannot survive without oxygen. The regulation of oxygen delivery to meet demands of tissues remains contentious. The study of supranormallevels of oxygen (hyperoxia/hyperoxaemia) may contribute to the understanding, as mechanisms that are active during normoxia and hypoxia (oxygen deficit) can be assumed to be at least similar, and compensatory mechanisms are kept to a minimum. Hyperoxaemic conditions are often seen clinically, but their effects in the human body are not fully known.

Hyperoxaemia causes vasoconstriction and reduction in heart rate and cardiac output. These effects are thought to be mediated through the endothelium as a result of either increased release, or activity, of vasoconstrictors such as serotonin (5-hydroxytryptamine, 5-HT)), or reduced activity of vasodilators such as prostaglandin E2 and nitric oxide (NO)). 5-HT and NO have been thought to have a central role.

To investigate both its effects and the underlying mechanisms we set up a human non-invasive normobaric hyperoxaemic model. We studied the effects of hyperoxaemia by measuring: peripheral blood flow by venous occlusion plethysmography; skin blood flow by laser Doppler perfusion imaging (LDI); cardiovascular assessments by echocardiography; and oxygen consumption (VO2) by an open circuit exchange system, CPX.

Plasma concentrations of 5-HT and ß-thromboglobulin (ß-TG) were measured to investigate the role of 5-HT during hyperoxaemia. To test the NO-hypothesis we achieved endothelium-dependent and endothelium-independent vasodilatation, using acetylcholine (ACh), and sodium nitroprusside (SNP) iontophoresis, respectively.

Mean calf blood flow decreased linearly to as much as -20% during oxygen breathing. Heart rate and cardiac output decreased, systemic vascular resistance increased, and blood pressure remained unchanged. Hyperoxaemia lessened vasodilatation in the skin induced by current (iontophoresis) and an anaesthetic agent (EMLA®-cream). There was no significant increase in concentrations of either 5-HT or ß-TG during hyperoxia, compared with air. Endothelium-dependent vasodilatation (ACh) was significantly reduced by breathing 100% oxygen. Vitamin C taken orally abolished the effects of oxygen. Hyperoxia did not affect endothelium-independent vasodilatation (SNP).

Hyperoxia affected most parts of the cardiovascular system in man, including perfusion in the skin. Probably the first and most pronounced effect was peripheral vasoconstriction, which could be seen within minutes. Heart rate and cardiac output decreased, possibly secondary to the vasoconstriction, so as to keep the blood pressure constant. There was no evidence that 5-HT had an important role in hyperoxia-mediated responses. On the contrary, the most likely hypothesis is that hyperoxic vasoconstriction is mediated by inhibition of synthesis of NO by free oxygen radicals inside the endothelial cells.

Place, publisher, year, edition, pages
Linköping: Larsson Offsettryck , 2005. , 49 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 891
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-31534Local ID: 17333ISBN: 91-85299-00-6 (print)OAI: oai:DiVA.org:liu-31534DiVA: diva2:252357
Public defence
2005-04-22, Berzeliussalen, Hälsouniversitetets bibliotek, Linköping, 13:00 (Swedish)
Opponent
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2012-10-03Bibliographically approved
List of papers
1. Acute hyperoxaemia-induced effects on regional blood flow, oxygen consumption and central circulation in man
Open this publication in new window or tab >>Acute hyperoxaemia-induced effects on regional blood flow, oxygen consumption and central circulation in man
2005 (English)In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 183, no 3, 231-240 p.Article in journal (Refereed) Published
Abstract [en]

Aim:  Despite numerous in vitro and animal studies, circulatory effects and mechanisms responsible for the vasoconstriction seen during hyperoxaemia are yet to be ascertained. The present study set out to: (i) set up a non-invasive human model for the study of hyperoxia-induced cardiovascular effects, (ii) describe the dynamics of this effect and (iii) determine whether hyperoxaemia also, by vasoconstriction alters oxygen consumption (O2).

Methods:  The study comprised four experiments (A, B, C and D) on healthy volunteers examined before, during and after 100% oxygen breathing. A: Blood flow (mL min−1·100 mL−1 tissue), venous occlusion plethysmography was assessed (n = 12). B: Blood flow was recorded with increasing transcutaneous oxygen tension (PtcO2) levels (dose–response) (n = 8). C: Heart rate (HR), stroke volume, cardiac output (CO) and systemic vascular resistance (SVR) was assessed using echocardiography (n = 8). D: O2 was measured using an open circuit technique when breathing an air-O2 mix (fraction of inhaled oxygen: FiO2 = 0.58) (n = 8).

Results:  Calf blood flow decreased 30% during O2 breathing. The decrease in calf blood flow was found to be oxygen dose dependent. A similar magnitude, as for the peripheral circulation, of the effect on central parameters (HR/CO and SVR) and in the time relationship was noted. Hyperoxia did not change O2. An average of 207 (93) mL O2 per subject was washed in during the experiments.

Conclusion:  This model appears suitable for the investigation of O2-related effects on the central and peripheral circulation in man. Our findings, based on a more comprehensive (central/peripheral circulation examination) evaluation than earlier made, suggest significant circulatory effects of hyperoxia. Further studies are warranted to elucidate the underlying mechanisms.

Keyword
blood flow, consumption, hyperoxaemia, hyperoxia, oxygen, vasoconstriction
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24768 (URN)10.1111/j.1365-201X.2005.01405.x (DOI)7029 (Local ID)7029 (Archive number)7029 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-10-02Bibliographically approved
2. Hyperoxia decreases cutaneous blood flow in high-perfusion areas
Open this publication in new window or tab >>Hyperoxia decreases cutaneous blood flow in high-perfusion areas
2007 (English)In: Microvascular Research, ISSN 0026-2862, E-ISSN 1095-9319, Vol. 74, no 1, 15-22 p.Article in journal (Refereed) Published
Abstract [en]

The mechanism by which hyperoxia decreases blood flow is still not understood. Hyperoxemia-induced vasoconstriction is known to occur in many organs, including brain and retina, skeletal muscle, and myocardium. Whether this also occurs in skin is unknown.

This study was conducted in healthy volunteers exposed intermittently to 100% oxygen (FIO2 1.0). Perfusion of forearm skin was measured by laser Doppler imaging (LDI). In series 1, it was measured in 7 subjects before, during, and after 15 min of oxygen breathing. In series 2, flow was measured, also during air and O2 breathing, after perfusion was raised by (a) sympathetic blockade (induced by a topically applied local anesthetic) (n = 9) and by (b) current-induced vasodilation (n = 8).

In normal unperturbed skin, there was no significant change with hyperoxia. When basal perfusion was raised by topical anesthesia or by current, there was also no change in mean perfusion overall with hyperoxia. However, areas with the highest perfusion (upper decile) showed a significant perfusion decrement with hyperoxia (− 30% and − 20%, respectively; p < 0.001).

Vasoconstriction with hyperoxia has been demonstrated in human skin. The fact that it is observed only when flow is increased above basal levels and then only in high-flow vessels suggests that cutaneous blood flow control is primarily regulated by variables other than oxygen.

National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-39470 (URN)10.1016/j.mvr.2007.02.001 (DOI)48745 (Local ID)48745 (Archive number)48745 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-03-20Bibliographically approved
3. Hyperoxaemia does not change concentrations of serotonin and beta‐thromboglobulin in blood of healthy humans
Open this publication in new window or tab >>Hyperoxaemia does not change concentrations of serotonin and beta‐thromboglobulin in blood of healthy humans
2004 (English)In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, Vol. 64, no 2, 81-85 p.Article in journal (Refereed) Published
Abstract [en]

Background: The mechanisms of oxygen‐induced effects on blood vessels (vasoconstriction in hyperoxaemia and vasodilatation during hypoxaemia) are uncertain. Many investigators have suggested that the vasoconstriction seen during hyperoxia/hyperoxaemia is mediated through the endothelium as a result of either increased release or activity of vasoconstrictors (oxygen radicals, endothelin, norepinephrine, angiotensin II, or serotonin (5‐HT)), or reduced activity of vasodilators (prostaglandin E2 and nitric oxide). Serotonin has been assumed to have a central role.

Methods: Eight healthy volunteers were exposed to FiO2 of 1.0 for 20 min and serum concentrations of serotonin and activated platelets were measured (indicated by concentrations of β‐thromboglobulin (β‐TG)).

Results. During hyperoxaemia in humans, serum concentrations of serotonin and β‐TG remained unchanged.

Conclusion: If serotonin is involved in oxygen‐induced vasoconstriction, the mechanism is more likely to be either a potentiating effect of serotonin on other vasoconstrictors or increased activity of serotonin on its receptor.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24029 (URN)10.1080/00365510410004137 (DOI)3584 (Local ID)3584 (Archive number)3584 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-10-03Bibliographically approved
4. Hyperoxia inhibits production of endothelial nitric oxide in humans
Open this publication in new window or tab >>Hyperoxia inhibits production of endothelial nitric oxide in humans
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Hypceoxia causes vasoconstriction in most tissues, but the mechanisms have yet to be elucidated. One hypothesis is that hyperoxia affects the production of free oxygen radicals (ROS), which reduce the concentration of the vasorelaxing agent nitric oxide (NO). It is not clear whether ROS reduce the synthesis of NO or inactivate NO that is already present. We investigated the effects of breathing 100% oxygen on NO-mediated vasodilation. Iontophoresis was used to deliver acetylcholine (ACh) (which stimulates endothelium-dependent production of NO) and sodium nitroprusside (SNP) (a NO-donor) through the skin of healthy volunteers (n=9). The blood flow in the skin was measured with a laser Doppler perfusion imager and dose-response curves were plotted. The drug dose at which 50% of the total perfusion increase was reached was calculated (ED50). The ED50 was significantly higher (right-shifted curve) while breathing oxygen compared with breathing air, when ACh was given by iontophoresis (95% CI 0.26 to 2.2). When ACh iontophoresis was preceded by oral intake of vitamin C (2.5 g daily for 3 days), this effect was abolished. Hyperoxla had no effect on vasodilation after iontophoresis with SNP. These results favour the hypothesis that hyperoxic vasoconstriction is mediated through inhibition of synthesis of NO by free oxygen radicals inside the endothelial cells.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-83825 (URN)
Available from: 2012-10-02 Created: 2012-10-02 Last updated: 2012-10-03Bibliographically approved

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