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.
Linköping: Larsson Offsettryck , 2005. , 49 p.
2005-04-22, Berzeliussalen, Hälsouniversitetets bibliotek, Linköping, 13:00 (Swedish)