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Spontaneous fluctuations of oxygen tension in tissue is similar to vasomotion of isolated pressurized arterioles

University of British Columbia

The underlying mechanism of formation of spontaneous oscillations in tissue oxygen tension and their physiological significance remain unknown. The working hypothesis of this study were that the oxygen fluctuations are based on arteriolar vasomotion and that the frequency of oscillations in tissue oxygen tension is similar to spontaneous vasomotion of isolated pressurized arterioles. In addition we investigated whether oxygen fluctuations are altered under pathological conditions such as in malignant tissue. In this study, pO2 oscillations in the brain and skeletal muscles of rats were measured with an Eppendorf Oxygen electrode. Fluctuations in pO2 and changes in local temperature were coherent. These fluctuations did not correlate with heart rate, respiration rate or electroencephalogram (EEG). Surgical sectioning of the sciatic nerve and intravenus (i.v.) injection of the ganglion blocker, mecamylamine, did not alter pO2 oscillations in skeletal muscle. The histology of blood vessels in the measurement areas was assessed by light microscopy. Arterioles from muscle and brain surrounding the electrode track, were dissected, cannulated and pressurized in a myograph. Spontaneous oscillations were observed at normal physiological intravascular pressure. The frequency of spontaneous oscillations in vitro matched the frequency of pO2 fluctuations in vivo. Pharmacological studies of these oscillations show that local administration of phenylephrine (PE), an α-adrenoreceptor agonist to skeletal muscle, in vivo, increased the amplitude and frequency of pO2 oscillations but had only minor effects on oscillations in brain. Prostaglandin (PGFα1) increased the amplitude of these oscillations in the brain but had only a moderate effect in skeletal muscles. Similar results were observed when phenylephrine and U46619, a thromboxane analogue, were administered to isolated pressurized arterioles. L-type calcium channel antagonist, nifedipine was shown to decrease the frequency and amplitude of these oscillations both in vivo and in vitro. In mice implanted with squamous cell carcinoma (SCCVII) tumours, pO2 fluctuations (1-3 c/min) were observed in subcutaneous control and peripheral tumour tissue (2 c/min). These fluctuations were absent in most central zones close to necrosis areas. Injection of nicotinamide increased pO2 significantly (p<0.01) and also reinitiated pO2 fluctuations in 5 out of 10 hypoxic tumour areas. In conclusion, oscillations of oxygen tension recorded in tissue are similar to spontaneous vasomotion of isolated pressurized arterioles surrounding the electrode. These fluctuations are altered in hypoxic areas of malignant tissue.

Thesis/Dissertation

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2009-07-17

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http://hdl.handle.net/2429/10927

Pharmacology and Therapeutics

University of British Columbia

UBCV

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