Potentiated hormonal responses in a model of traumatic injury

Abstract

Although major trauma often involves repeated insults, few studies have examined the endocrine response to repeated injury. In earlier work, we described potentiated responses of circulating adrenocorticotropin (ACTH) and adrenal secretion of cortisol, epinephrine, and norepinephrine to the second of two small hemorrhages separated by 24 hr. To investigate the response of other hormones to repeated hemorrhage and to examine possible hormonal interactions in a shorter, more clinically relevant time frame, we placed chronic adrenal vein cannulas in eight splenectomized, trained dogs. Each animal was bled 10% of measured blood volume with reinfusion of shed blood at 30 min. The hemorrhage was repeated 5 hr later. Initial hemorrhage led to a small but significant increase in adrenal cortisol secretion and circulating ACTH, vasopressin (AVP), angiotensin II (AII), and plasma renin activity (PRA). Although a 5-hr time interval between stimuli is commonly thought to lead to cortisol feedback, the circulating ACTH and adrenal cortisol secretory responses to the second hemorrhage were exaggerated in comparison to their initial responses. Similarly, the AVP response to the second hemorrhage was also increased. In contrast, the responses of PRA and AII to the second hemorrhage were not greater than their responses to the initial hemorrhage. No differences in measured blood volume before each hemorrhage or in the heart rate and arterial pressure responses to hemorrhage were observed that could explain the potentiated hormonal responses. Thus, potentiated responses of cortisol, ACTH, and AVP, but not of PRA and AII, were observed in a model of trauma that emphasizes repeated injury in a clinically relevant time frame. Although the physiologic significance of this endocrine phenomenon is unclear, potentiated humoral responses may have important clinical implications.