ObjectiveTo determine the effects of titrated arginine vasopressin (AVP) alone or in combination with norepinephrine (NE) on hemodynamics and oxygen transport in healthy and endotoxemic sheep.DesignProspective controlled trial.SettingUniversity research laboratory.SubjectsSix adult ewes.InterventionsHealthy sheep received AVP as a titrated infusion, initiated with 0.6 units/hr and increased by 0.6 units/hr every 15 mins, either until mean arterial pressure was increased by 20 mm Hg vs. baseline or a maximum of 3.6 units/hr was administered. After 90 mins, AVP infusion was continued with the investigated dosage, and NE (0.2 &mgr;g·kg−1·min−1) was also infused for 90 mins. After a 24-hr period of recovery, endotoxemia was induced and maintained (Salmonella typhosaendotoxin, 10 ng·kg−1·min−1) in the same sheep for the next 19 hrs. After 16 hrs of endotoxemia, AVP and NE were administered as described previously.Measurements and Main ResultsHemodynamics were obtained at baseline, every 15 mins during the titration period, and 60 and 90 mins after additional NE infusion. Variables of oxygen transport were calculated before and after the titration period. In healthy and endotoxemic sheep, AVP reduced heart rate and cardiac index (p< .001) and compromised oxygen delivery (p< .001) and oxygen consumption (healthy sheep,p= .003; endotoxemic sheep,p< .001). Vasopressin infusion did not alter mean pulmonary arterial pressure but increased pulmonary vascular resistance index in both groups (p< .001). Additional infusion of NE further augmented mean arterial pressure and increased cardiac index during endotoxemia (p< .001). This was accompanied by an increase in oxygen delivery and consumption (p< .05 each).ConclusionsDuring ovine endotoxemia, AVP decreased cardiac index, compromised oxygen delivery, and increased pulmonary vascular resistance index. These side effects may limit its use as a sole vasopressor during sepsis. Potentially, a simultaneous infusion of AVP and NE could represent a useful therapeutic option.