Vasopressin‐Altered Glycemic Control May Lead to Metabolic Disorders of Severe Hemorrhagic Shock

Abstract

Metabolic disorders associated with trauma and hemorrhage typically follow an early hyperglycemic reflex aimed at increasing brain blood glucose in the face of oxygen debt. The hyperglycemic reflex is believed to be initiated by hypoxia‐induced carotidbody stimulation via a vasopressin (VP) V1a receptor mechanism. We hypothesized that elevated circulating VP levels released in response to severe shock contribute not only to restoring blood pressure, but may also prolong altered glycemic control. Thus, we examined VP influence on glucose regulation after severe oxygen debt from hemorrhagic shock using Yorkshire cross pigs (n=29, body weight 31.1+0.3 kg). Rapid hemorrhage (30 ml/kg bloodshed over 20 minutes) was induced to cause a 50% drop in mean arterial pressure and an oxygen debt of 68+5 ml/kg. Blood glucose levels rose from 124+10 mg/dl at baseline to 174+10mg/dl after hemorrhage (p<0.01), with accompanying increases in VP, epinephrine, glucagon, and insulin. Relationships between blood glucose, VP, epinephrine, glucagon, insulin, pancreatic blood flow and liver blood flow were examined. Multiple regression analysis of glycemic control from baseline through the end of hemorrhage indicated that glucose levels were strongly associated with VP and epinephrine, and inversely related to glucagon which correlated with VP (p<0.01). VP and pancreatic blood flow remained negatively correlated in all phases of baseline, hemorrhage and resuscitation with exogenous VP (30 ng/kg/min i.v., n=7). Thus pancreatic blood flow was significantly lower (p<0.01) with VP‐treated pigs (0.14+0.02 ml/kg/min) than in pigs that were resuscitated with normal saline where pancreatic blood flow (0.36+0.04ml/kg/min, n=10) did not further decrease. Exogenous VP during resuscitation also stimulated liver blood flow, and seemed to keep glucagon from decreasing despite the decreased pancreatic blood flow. VP did not affect insulin levels. Results suggest that VP mediates a hyperglycemic response in severe hemorrhagic shock via influence on glucagon secretion. If hyperglycemia continues beyond this acute response to hemorrhage, long‐term metabolic disorders could develop which would lead to tissue oxidative damage and contribute to trauma‐induced multisystem organ failure. Strategies for critical care management of hemorrhagic shock need to incorporate understanding of VP‐induced metabolic alterations of glycemic control.Support or Funding InformationThis project was supported by U.S. Army Medical Research and Materiel Command Congressionally Directed Medical Research Program grant #DAMD17‐03‐1‐0072. The views expressed in this abstract are those of the authors and do not reflect the official policy or position of the Department of the Army, Department of Defense, or the U.S. Government.