title: CSF acidosis augments ventilation through cholinergic mechanisms.
abstract: Ventilation is influenced by the acid-base status of the brain extracellular fluids (ECF). CO2 may affect ventilation independent of changes in H+. Whether the acidic condition directly alters neuronal firing or indirectly alters neuronal firing through changes in endogenous neurotransmitters remains unclear. In this work, ventriculocisternal perfusion (VCP) was used in anesthetized (pentobarbital sodium, 30 mg/kg) spontaneously breathing dogs to study the ventilatory effects of acetylcholine (ACh), eucapnic acidic (pH approximately 7.0) cerebrospinal fluid (CSF), and hypercapnic acidic (pH approximately 7.1) CSF in the absence and presence of atropine (ATR). Each animal served as its own control. Base line was defined during VCP with control mock CSF (pH approximately 7.4). With ATR (4.8 mM) there was an insignificant downward trend in minute ventilation (VE). ACh (6.6 mM) increased VE 53% (n = 12, P less than 0.01), eucapnic acidic CSF increased VE 41% (n = 12, P less than 0.01), and hypercapnic acidic CSF increased VE 47% (n = 6, P less than 0.01). These positive effects on ventilation were not seen in the presence of ATR. This suggests that acidic brain ECF activates ventilatory neurons through muscarinic cholinergic mechanisms. Higher concentrations of ACh increased ventilation in a concentration-dependent manner. Higher concentrations of ATR decreased ventilation progressively, resulting in apnea. The results suggest that ACh plays a significant role in the central augmentation of ventilation when the brain ECF is made acidic by either increasing CSF PCO2 or decreasing CSF bicarbonate.
authors.affiliation: Medical Services (Pulmonary Unit), Massachusetts General Hospital, Boston 02114.
authors.forename: M D
authors.initials: MD
authors.lastname: Burton
authors.forename: D C
authors.initials: DC
authors.lastname: Johnson
authors.forename: H
authors.initials: H
authors.lastname: Kazemi
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000136:Acid-Base Equilibrium / Q000187:drug effects*; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D001639:Bicarbonates / Q000134:cerebrospinal fluid*; D002245:Carbon Dioxide / Q000134:cerebrospinal fluid*; D004285:Dogs; D012119:Respiration / Q000187:drug effects*
chemical_list: D001639:Bicarbonates; D002245:Carbon Dioxide; D001285:Atropine; D000109:Acetylcholine