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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Effect in cat of locus coeruleus lesions on the response of cerebral blood flow and cardiac output to altered paCO2.

In pentobarbital-anesthetized cats, over arterial paCO2 values of 20-60 mm Hg, cerebral blood flow (CBF, Xenon) and cardiac output (CO, thermal dilution) show positively inflicted curves with slopes significantly greater than zero. To examine the role of the locus coeruleus (LC) in these responses, bilateral stereotactic thermo-coagulation lesions of the LC were made. The effect of lesions confirmed to involve the LC bilaterally (n = 10), were compared with the effects of misdirected lesions placed in the cerebellum and lateral to the LC (n = 10) and sham lesions (n = 10). Ten days after the lesioning procedure, the animals were re-anesthetized with pentobarbital and paCO2 response curves were determined for CBF and CO prior to and following intravenous administration of propranolol (1 mg/kg, i.v.). The results obtained with the sham-operated animals and the animals with lesions outside of the LC were indistinguishable. Bilateral LC lesions had no significant effect on normocapnic CBF as compared to control animals. They did, however, significantly reduce the slope of the CBF paCO2 response curve. Propranolol produced a significant reduction in CBF in lesioned and non-lesioned animals measured at all levels of pCO2 and did not alter the slope of the pCO2 response curve for any group as compared to predrug values. Bilateral lesions of the LC did not significantly alter either normocapnic CO or the slope of the CO-paCO2 relationship, but did reduce the elevation in mean arterial blood pressure otherwise observed during hypercarbia. Measurement of norepinephrine levels in cortex indicate a close correlation between the ability of the lesion to reduce norepinephrine content and produce the observed physiological effects. The results of these experiments suggest that the hypercapnic response of CBF, but not CO to arterial paCO2 is modulated by systems which traverse the dorsal brainstem. The role of the locus coeruleus-catecholamine cell bodies in this effect, however, must be considered speculative until further transmitter-selective interventions are carried out.[1]


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