Leptin and the perioperative neuroendocrinological stress responses

The human response to surgical stress is characterized by massive release o f neuroendocrine hormones, provoking catabolism, thermogenesis, and hypergl ycemia. Considering the possible adverse outcomes of excessive stress hormo nes, understanding various components of the stress response may improve ma nagement of postoperative morbidity. Leptin, initially described as an adip ocyte-derived signaling factor, may also play an important role in regulati ng the hypothalamo-pituitary-adrenocortical axis. In phase I, plasma leptin and cortisol were measured in women before, durin g, and after total abdominal hysterectomy. The anesthetic technique was str ictly controlled, balanced anesthesia. In phase II, plasma leptin and corti sol levels were measured in cardiac surgery patients. These subjects were a nesthetized with a high dose opioid technique that blunts the intraoperativ e surgical stress response. In phase 1, mean leptin levels did not change o ver the week before surgery, had a maximal decrease to 49% of baseline 2 h after surgery, and increased to just above baseline 24 h postoperatively. C ortisol was 176% of the baseline just before surgery, peaked at 2 h after s urgery (383%), and remained elevated 24 h (200%) and 48 h (165%) after surg ery. During the first 2 h of surgery, the decrease in leptin parallels the increase in cortisol. In phase II, high dose fentanyl limited both the cort isol increase and the leptin decrease; thus, the ratio of cortisol increase to leptin decrease was similar for the cardiac patients and the hysterecto my patients. These data indicate that leptin has a role in the surgically induced acute stress response in humans. Early in surgery the decrease in leptin parallel s the increase in cortisol. This suggests a possible relationship between t he neurobiology of these two systems, which could have important implicatio ns for regulation of the neuroendocrine response to surgical stress.