INTERACTIONS OF MORPHINE SULFATE AND SODIUM SALICYLATE ON RESPIRATION IN CATS

¹ Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire

Cats were anesthetized with urethane and placed in a body plethysmograph that allowed the head and forelimbs to be exteriorized. Respiratory excursions, the end-expiratory percentage of CO² and blood pressure were recorded continuously. Arterial blood pH was measured intermittently with 0.1-ml samples. The carbon dioxide apneic threshold was determined by applying positive pressure hyperventilation to reach the hypocapnic respiratory cut-off level. Morphine (1-10 mg/kg iv.) caused a reduction in respiratory rate but not in depth, an elevation in the resting percentage of CO² and a fall in blood pH. Salicylate (a total of 400 mg/kg iv.) by itself elicited an increase in rate and depth of ventilation. but after morphine could cause only an increase in depth. However, morphine continued to be effective in reducing the respiratory rate after pretreatment with salicylate. The drug effects on respiration were not related to the apneic threshold, which for the most part remained unchanged. The combined drug effects were essentially the same in vagotomized cats and in cats with lesions of the area postrema as in intact animals. The effects of morphine are attributed to a selective depressant action on the medullary respiratory pacemaker with no apparent influence on CO² detection. The effects of salicylate are best explained as being due to an upstream stimulant action on the pontine respiratory modulator.