Studies were performed to define the CNS acid-base status in the fetal lamb, as well as the contribution of CNS mechanisms in the initiation and control of breathing in the newly born lamb. The average CSF pH in term fetal lambs was found to be similar to that in young lambs as well as man. When fetal CSF hydrogen ion concentration was noted to be increased, or when perfusion of the ventral lateral medulla with mock CSF high in hydrogen ion concentration was carried out, no respiratory activity was noted. This suggests that the central response to hydrogen ion concentration, which is responsible for control of respiration in the breathing animal, may not be operative in the fetal state. However, in the physiologic setting of these experiments, the onset of breathing was primarily a central function which was little affected by peripheral chemoreceptor or baroreceptor discharge, as animals with their carotid sinus and vagal nerves divided initiated respiration as consistently as controls. Once breathing has been initiated, the central response to hypercarbic breathing could be demonstrated in the absence of any possible peripheral chemoreceptor influence.

ExtractIncreased activity of the carotid chemorecep tors from hypoxia and hypercarbia, induced by occlusion of the umbilical cord, has importance in initiating effective respiration of the term lamb. The state of hypoxia and hypercarbia continuing after birth should also evoke strong stimulation from the carotid glomi. The present experiments measure the effects on ventilation resulting from interruption of carotid chemoreceptor stimulation to the respiratory center by division of each carotid sinus nerve of the lamb during the newborn period.Ewes were given spinal anesthesia and each lamb was partly removed from the uterus to permit an operative approach through the neck. The carotid sinus nerves were exposed and tagged with loose threads to facilitate division of the nerve at a later stage. The lamb was then delivered, its umbilical cord clamped, and its inspiratory volume measured by pneumotachometric techniques.Each of the seven lambs studied was permitted to establish respiration before its first carotid sinus nerve was divided. The time intervals between birth and division of the first nerves varied from 5.5 to 38.5 minutes after birth. The second nerves were divided several minutes later when respiration had recovered from the effects of division of the first nerve. A significant fall in ventilation was observed within 50 seconds after division of each carotid sinus nerve. Improved ventilation began to occur in some animals 150 seconds later, and occurred in all animals within several minutes after division of each nerve. Levels of Pc>2> pH and PCO2 i n carotid artery blood before nerve division revealed hypoxia, hypercarbia and acidosis; this aberrant state became worse during the period of diminished ventilation. The minimal changes in heart rate and blood pressure resulting from interruption of baroreceptor fibers were insufficient to influence respiration. Speculation

Respiratory patterns after deliberate cord occlusion of four fetal lambs with bilaterally divided carotid sinus nerves were compared with those of four control lambs subjected to similar surgery without actual division of the nerves. The animals with divided carotid sinus nerves did not develop sustained rhythmic respiration and showed fall in Po2, which persisted, and progressive fall in pH and rise in Pco2 during the 10-minute period of observation after cord occlusion. The mock-operated animals developed sustained rhythmic respirations and showed rise in Po2, fall in Pco2 and less fall in pH than the animals with divided carotid sinus nerves. This striking inability of the lambs deprived of carotid chemoreceptor function to initiate effective respiration indicates that this mechanism has an important role in the initiation of breathing under these conditions.

Previous reports (1, 2) indicate that reduced urine flow and free-water clearance resulted from occlusion of the carotid arteries below the junctions of the superior thyroid and common carotid arteries in hydrated dogs, whereas occlusion above innervated or below denervated junctions was ineffective. Since in all these instances the carotid sinus reflex was activated, the conclusion was drawn that the carotid sinus is not the receptor site involved in the initiation of the reflex antidiuresis. Additional evidence for the validity of this conclusion is presented in the present report which concerns the effect of carotid occlusion below thyrocarotid junctions on several indices of renal function during water diuresis in dogs with transected sinus nerves.Methods. Mongrel dogs of both sexes (12.7-16.8 kg) , vaccinated against distemper and infectious hepatitis and treated for intestinal parasites, were deprived of food for 18 hr and anesthetized with intravenous pentobarbital sodium (30 mp/kg, with supplementation as required). After a priming intravenous injection of creatinine and p-aminohippurate (PAH), warm 3.5% glucose in water with sustaining amounts of these substances was infused intravenously by pump at a rate of 2.5 ml/min for the duration of the experiment. Preparation of animals for the collection of urine from cannulated ureters and for subsequent nontraumatic

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