Pentobarbital causes cardiorespiratory depression by interacting with a GABAergic system at the ventral surface of the medulla.
A tonically active gamma-aminobutyric acid (GABA) system at Schlaefke's area (intermediate area) on the ventral surface of the medulla exerts control over cardiorespiratory function. This is the same site where Feldberg and Guertzenstein elicited pentobarbital-induced hypotension. To determine whether pentobarbital-induced cardiorespiratory depression is mediated by a GABAergic mechanism at this site, we applied this agent locally to the intermediate area in eight chloralose-anesthetized cats while monitoring respiratory activity, blood pressure and heart rate. Pentobarbital (0.5-1.5 mg) reduced minute ventilation from 383 +/- 19 to 227 +/- 31 ml/min (P less than .05) by reducing tidal volume from 29.8 +/- 2.4 to 16.1 +/- 1.6 ml (P less than .05), without changing respiratory rate. Mean blood pressure and heart rate were reduced from 150 +/- 16 mm Hg and 182 +/- 8 beats/min to 73 +/- 16 mm Hg and 136 +/- 12 beats/min (P less than .05), respectively. Respiratory depression culminated in apnea in each animal tested. Bicuculline applied to the intermediate area in doses that selectively counteract GABA-induced apnea (5.0-17.5 micrograms) reestablished breathing, mean arterial pressure and heart rate to values equal to or greater than control levels. This dose range of bicuculline had no effect on heroin-induced respiratory depression. Cardiorespiratory depression observed with i.v. administration of pentobarbital in four cats was also reversed by bicuculline (10-20 micrograms) applied to the intermediate area. These results indicate that pentobarbital acts at the intermediate area to activate a GABAergic system resulting in cardiorespiratory depression.
D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002415:Cats; D006339:Heart Rate / Q000187:drug effects*; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism*; D010424:Pentobarbital / Q000494:pharmacology*; D012119:Respiration / Q000187:drug effects*; D013990:Tidal Volume; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
C017069:bicuculline methiodide; D005680:gamma-Aminobutyric Acid; D010424:Pentobarbital; D001640:Bicuculline