title: Central cholinergic control of cerebral blood flow in the baboon. Effect of cholinesterase inhibition with neostigmine on autoregulation and CO2 responsiveness.
abstract: Cerebral autoregulation and vastomotor responsiveness to carbon dioxide (CO2) were measured quantitatively by the use of the autoregulation index and chemical index, respectively, in normal baboons before and after intravertebral and intracarotid infusion of the anticholinesterase agent, neostigmine methylsufate (Prostigmin). Continuous measurements were made of cerebral blood flow (measured as bilateral internal jugular venous outflow), arterial and cerebral venous pO2 and pCO2, cerebral arteriovenous oxygen differences, and endotracheal CO2. The effect of intravertebral infusion of neostigmine (12.5 mug/kg body weight) was compared to intravertebral infusion of neostigmine (25 mug/kg body weight) for assessment of any specific action of the drug on a hypothetical cholinergic vasomotor center, presumed to be located in the territory of the vertebrobasilar supply. No significant or persistent changes in cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) followed either intravertebral or intracarotid infusion of neostigmine. Cerebral vascular resistance (CVR) and cerebral perfusion pressure (CPP), however, decreased significantly after intravertebral infusion. Cerebral autoregulatory vasoconstriction during increases of CCP was significantly reduced following both intravertebral and intracarotid infusion. Cerebral autoregulatory vasodilatation was not altered as CPP was lowered. Cerebral vasodilatory reactivity to CO2 inhalation was significantly enhanced following intravertebral neostigime but not following intracarotid neostigmine. Cerebral vasoconstrictive response to hyperventilation was not influenced by neostigmine. These results support the view that central cholinergic cerebrovascular influences exist, and are vasodilatory in nature.
mesh_terms: D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D001794:Blood Pressure; D001921:Brain / Q000378:metabolism; D002245:Carbon Dioxide; D002339:Carotid Arteries; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D002802:Cholinesterases / Q000097:blood; D006439:Hemodynamics; D006706:Homeostasis; D007269:Injections, Intra-Arterial; D008954:Models, Biological; D009388:Neostigmine / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D010215:Papio; D014666:Vasomotor System / Q000187:drug effects*; D014690:Venous Pressure; D014711:Vertebral Artery
chemical_list: D002245:Carbon Dioxide; D009388:Neostigmine; D002802:Cholinesterases; D000109:Acetylcholine