Background: Septic shock is a life-threatening condition caused by a severe blood infection, resulting in insufficient circulation to the body¿s organs. In about 50' of septic shock cases, low blood pressure is unresponsive to traditional blood pressure elevating drugs. In such cases, mortality rates approach 100' due to complications of multiple organ failure. Recently, vasopressin has been shown to increase blood pressure during septic shock when other pressor agents fail. Previous work in our laboratory has shown that vasopressin differentially modulates regional blood flow to various organs. It is possible that vasopressin may be beneficial in the treatment of septic shock due to its ability to redirect blood flow to vital organs.

Objective/Hypothesis: This project will test the hypothesis that vasopressin infusion during septic shock leads to improved hemodynamics and preservation of vital organ function by increasing perfusion to specific vascular beds.

Specific Aims: (1) To compare the effects of vasopressin on perfusion to vital organs with that of norepinephrine and dopamine during septic shock. (2) To elucidate mechanisms by which vasopressin helps regulate blood flow and preserve organ function during septic shock via quantification of local vasopressin and vasopressin receptor synthesis in arteries and veins in different vascular beds.

Study Design: Measurements of hemodynamics, regional blood flow via colored microsphere analysis, and hormone responses will be used to evaluate the effects of vasopressin in a pig model of septic shock induced by bacterial endotoxin. Mechanisms behind regional blood flow distribution during septic shock will be examined with assessment of blood vessel mRNA for vasopressin and vasopressin receptors.

Relevance: Septic shock is a high-risk disease of infection seen in all Army hospitals. Susceptibility of battlefield wounds to infections and the possibility of soldier exposure to biological warfare agents makes the treatment of septic shock a significant ¿military relevant disease management¿ concern. A better understanding of the effects of vasopressin on organ perfusion in comparison to other commonly used pressor agents is essential to clarifying the role of vasopressin in the treatment of septic shock in clinical practice.