Effect of surgery on the pituitary-adrenal response to repeated hemorrhage

We studied the effect of surgery on hemorrhage-induced facilitation in the pituitary-adrenal system using repeated hemorrhage in chronically prepared dogs. Animals underwent splenectomy and adrenal venous and femoral arterial catheterization. Two (day 2) or five (day 5) days later, animals were anesthetized with pentobarbital, respired, and subjected to two periods of hypovolemia (20% hemorrhage with reinfusion of shed blood at 30 min; H1 and H2) separated by 90 min. Arterial and adrenal venous blood was sampled, and adrenocorticotropic hormone (ACTH), arginine vasopressin (AVP), angiotensin II (ANG II), cortisol, and cortisol secretion were measured. On day 2, cortisol secretion increased similarly after H1 and H2, despite a smaller response of ACTH to H2. On day 5, neither ACTH nor cortisol secretion changed after H1, but both increased significantly after H2. The adrenal sensitivity to ACTH increased after H2 on day 2 and was similar after H2 on both days. AVP and ANG II increased similarly after H1 and H2 on each day but had larger responses on day 2. These results suggest 1) either surgery or initial hemorrhage can lead to enhanced pituitary-adrenal responses to subsequent hemorrhage, 2) this effect may have both central and adrenal components, 3) negative feedback may inhibit enhanced responses of ACTH in this model, 4) changes in adrenal sensitivity to ACTH may not depend on an initial pituitary-adrenal response and may not be blocked by increased circulating corticosteroids, and 5) differences in circulating AVP or ANG II do not account for facilitation in pituitary-adrenal responses.