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

In pentobarbital-anesthetized cats, over arterial p_aCO₂ values of 20–60 mm Hg, cerebral blood flow (CBF, Xenon) and cardiac output (CO, thermal dilution) show positively inflected 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 abd lateral to the LC (n= 10) and sham lesions (n= 10). Ted days after the lesioning procedure, the animals were re-anesthetized with pentobarbital and p_aCO₂ 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 p_aCO₂ 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 normacapnic CO or the slope of the CO-p_aCO₂ relationship, but did reduce the elevation in mean arterial blood pressure otherwise observed during hypercarbia. Measurement of norepinephrine levels in cortex indicate a close indicate a 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 p_aCO₂ 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.