RESPIRATORY EFFECTS OF ETHANOL AND PROCAINE INJECTED INTO THE CEREBROSPINAL FLUID OF THE BRAINSTEM IN CATS

Respiration was recorded plethysmographically. Drug injections were made through cannulas inserted stereotactically into the ventricular and subarachnoid spaces. Sufficient doses produced respiratory failure characterized by rapid progressive development of expiratory apnea in the case of ethanol and apneustic breathing in the case of procaine. Effects of the agents were best achieved through bilateral instillation in the subarachnoid space of the medulla oblongata and did not require drug contact with the ventricular lining. The basic response patterns were still elicitable after decerebration and interruption of the vagus and carotid sinus nerves and were not dependent upon general anesthesia. Effects of graded doses were assessed under steady-state conditions upon the tidal volume as a function of end-expiratory carbon dioxide. The alveolar tension of carbon dioxide was varied by administration of the gas to produce hypercapnia and by the use of hyperventilation to produce hypocapnia. Ethanol reduced the slope of the VT-log[C02] straight line relationship without altering the carbon dioxide stimulus threshold. Procaine, on the other hand, evoked a complex effect which included changes in slope and position and, maximally, an uncoupling of tidal volume from carbon dioxide drive. These effects are interpreted by control systems analogy as a simple reduction in "controller gain" produced by ethanol, but by an additional disturbance of "detector" function produced by procaine. No evidence was obtained for an essential action of the drugs upon a postulated chemosensitive site for carbon dioxide situated on the brainstem surface.