The purpose of this clinical study is to examine the role of vasopressin and norepinephrine in the treatment of septic shock and their impact on survival. Norepinephrine, a vasopressor, is the most commonly used clinical agent to reverse the lethal hypotension in patients with septic shock. A new therapy for sepsis has been the use of vasopressin to treat the hypotension associated with sepsis. Small studies have examined vasopressin in conjunction with norepinephrine and suggest that their use together may lower norepinephrine requirements in septic patients. High doses of either vasopressin or norepinephrine can lead to negative outcomes including decreased end organ perfusion and decreased cardiac output. It is believed that by combining these two drugs, there will be less vasoconstriction related organ injury and an increased benefit in survival rate. However, no clinical or animal study has examined the effect of norepinephrine, vasopressin or a combination on survival rate, blood pressure and organ injury. This is, in part, due to the lethality of the disease where withholding such therapies would be impossible. Of particular concern is that it is entirely possible that some of these vasopressors can improve blood pressure but adversely affect survival. L-NMMA, a vasopressor, increased blood pressure but worsened outcome in this model of sepsis. Unfortunately these results were confirmed in humans with septic shock. Previously, in a pilot study, we determined doses of each drug used alone that raised blood pressure but did not adversely affect survival rate. This study will examine the role of vasopressin and norepinephrine used alone and together in treating sepsis in the canine model. ? ? This study is a continuation of a previous study comparing the efficacy of epinephrine, norepinephrine and vasopressin in a bacterial peritonitis model of sepsis in conscious animals (Am J Physiol Heart Circ Physiol 287:H2545-H2554, 2004). In the last 18 months, a new model of sepsis has been developed using a sedated and ventilated model of intrabronchial instilled Staph. Aureus which reflects a large percentage of the septic infections requiring ventilation in the ICU. The use and efficacy of vasopressin and norepinephrine used alone or in combination on blood pressure, cardiac output and survival will be tested in this model of sepsis in the coming year.

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Potenza, Maria A; Marasciulo, Flora L; Chieppa, Delia Mitolo et al. (2005) Insulin resistance in spontaneously hypertensive rats is associated with endothelial dysfunction characterized by imbalance between NO and ET-1 production. Am J Physiol Heart Circ Physiol 289:H813-22
Minneci, Peter C; Deans, Katherine J; Banks, Steven M et al. (2004) Differing effects of epinephrine, norepinephrine, and vasopressin on survival in a canine model of septic shock. Am J Physiol Heart Circ Physiol 287:H2545-54