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1 An in vitro brainstem-spinal cord preparation of the newborn rat was used to examine the effects of neurotransmitters and transmitter candidates on respiratory frequency. 2 Spontaneous periodic depolarization of the spinal ventral roots of the 4th or 5th cervical segment was observed at a frequency of 5-15 min-' constantly for more than 5 h. The frequency of this depolarization was monitored as an index of the respiratory frequency. 3 An elevation of the concentration of Ca2+ or Mg2+ caused a decrease in the respiratory frequency, whereas an elevation of K+ concentration caused an increase. The frequency was also increased by a reduction of pH. The highest frequency was observed at 27-280C. 4 Dopamine, 5-hydroxytryptamine, histamine, acetylcholine, glutamic acid, substance P, and thyrotropin releasing hormone accelerated the respiratory frequency when applied by perfusion to the brainstem, whereas noradrenaline, y-aminobutyric acid, glycine, and [Met5] enkephalin and [Leu5] enkephalin slowed the frequency. Experiments with antagonists suggested that the stimulant effect of acetylcholine on respiratory frequency was mediated mainly by muscarinic receptors and the depressant effect of noradrenaline was mediated by a-adrenoceptors.

Regulatory mechanisms of the hypothalamo-pituitary-adrenal (H-P-A) axis during and after major abdominal surgery were studied in a group of patients who underwent upper abdominal surgery. We first examined the general profile of the changes of the H-P-A axis from the day before surgery to the seventh day after surgery. On the day of surgery, plasma levels of CRH, ACTH, and cortisol were all significantly elevated after skin incision (phase I). During the next 2 days, plasma cortisol levels remained significantly elevated, and the both plasma CRH and ACTH levels were suppressed below the control levels obtained on the day before surgery (phase II). Several additional studies, carried out to analyze the mechanism that maintains the high plasma cortisol levels, revealed the following features of the H-P-A axis during phase II. Plasma free cortisol levels in this phase were higher than those during the preoperative period. The exogenously administered hydrocortisone clearance rate in phase II did not differ from that observed on the day before surgery. Dexamethasone administration resulted in a decrease in plasma cortisol levels similar to that observed preoperatively. Conversely, the ACTH-stimulated cortisol increase was significantly greater in phase II than that observed preoperatively. These results suggest that during and after major surgical stress, the H-P-A axis undergoes a biphasic change in the pattern of the stress response and during the second phase, not the continuous hypothalamo-pituitary drive but the increased adrenal responsiveness to ACTH is responsible at least in part for maintaining the elevated plasma cortisol level.