Reserpine, Chlorpromazine and the Hypothalamus in Reactions to Oxygen at High Pressure

¹ From the Department of Physiology, University of Michigan, Ann Arbor, Michigan

Experiments were carried out on Sprague-Dawley rats to determine what effect reserpine and chlorpromazine might have on the toxic action of O₂ at high pressure (OHP). Serpasil (Ciba) administered intramuscularly in 10 daily doses of 0.075 mg/kg before the animal's exposure to O₂ at 85 lb. conferred some degree of protection against the O₂ toxicity as manifest by a less extensive pulmonary hemorrhage and edema and a lesser lung weight than that of the controls. Single doses of 0.35 mg/rat were less effective. Chlorpromazine administered in single doses of from 13–35 mg/kg body weight gave a more pronounced protection; it delayed the onset of minimal and severe neuromuscular reactions and diminished their severity. It prevented or diminished the severity of pulmonary hemorrhage congestion and edema; prevented or markedly diminished the increase in lung weight usually seen in OHP and lowered the mortality. It diminished vasoconstriction in the mesentery; lessened congestion in the heart and liver and diminished the severity of intestinal hypotonia and hypomotility as compared with that of the controls. The protective influence of these agents is ascribed to their reportedly suppressive action at the hypothalamic level and the consequential inhibition of the augmentative influence of a) the adrenal cortex and medulla and b) of the sympathetic nervous outflow. The greater effectiveness of chlorpromazine may be attributed to its additional strong antiepinephrine action and that it possibly lowers metabolism. The data support the view that the increased hypothalamic activity in OHP augments the O₂ toxicity through its influence on the hypophysis and adrenal cortex and through the sympathetic outflow to the adrenal medulla and adrenergic nerve endings; they also are in accord with the finding previously reported that peripheral sympathetic blocking agents afford some protection against the toxic action of OHP.