05 versus ST each; Table Table11).Mesenteric blood flowMesenteric blood flow decreased in all groups selleckchem Sunitinib (10 hours: P < 0.05 versus ST each; Table Table1)1) without any statistically significant differences among groups.Pulmonary gas exchange and global oxygen transportBesides a lower PaO2/FiO2 (arterial partial pressure of oxygen/fraction of inspired oxygen) ratio in the V2R-antagonist group compared with the placebo group at 4 hours (P = 0.039, Table Table2),2), there were no statistically significant differences between study groups in variables of pulmonary gas exchange and global oxygen transport (Table (Table22).Table 2Hematocrit, electrolytes, acid-base balance, and global oxygen transportCapillary leakageIn all study groups, septic shock was characterized by a marked decrease in plasma protein concentrations (ST: P < 0.

001 versus BL each) that progressed over the study period (8 hours: P < 0.001 versus ST each; Table Table3).3). At the same time, there were no statistical differences in hematocrit within or among groups (Table (Table2),2), suggesting adequate fluid resuscitation. Cumulative positive net fluid balance was similar with all three treatment regimes (V2R-antagonist: 19 �� 1 mL/kg per hour; AVP: 17 �� 1 mL/kg per hour; placebo: 18 �� 2 mL/kg per hour).Table 3Surrogate parameters of organ (dys)functionMetabolic changes and electrolytesSeptic shock was associated with decreases in arterial pH and base excess (P < 0.05 versus BL each and P < 0.001 versus BL each, respectively) and increases in arterial lactate concentrations (P < 0.

05 versus BL each) in all groups (Figure 3a,b and Table Table2).2). These metabolic changes progressed during the observation period (8 hours: P < 0.001 versus ST each). However, the increase in arterial lactate concentration was attenuated (8 and 10 hours: P < 0.01 each), arterial base excess was less negative, and pH values were higher in the selective V2R-antagonist group as compared with the AVP and placebo groups after 8 hours (P < 0.05 each). Plasma concentrations of potassium and chloride increased in all groups during the study period (P < 0.05 versus ST each) without significant differences among groups.Figure 3Arterial base excess (a) and arterial lactate concentrations (b). ?P < 0.05 versus baseline (BL); *P < 0.05 versus shock time (ST); ?P < 0.05 versus placebo; ��P < 0.05 versus arginine vasopressin .

..Laboratory variables of organ function and arginine vasopressin plasma levelsAlanine aminotransferase and aspartate aminotransferase activity as well as plasma concentrations of bilirubin were reduced by the selective V2R-antagonist as compared with placebo animals Batimastat (8 hours: P < 0.05 each; Table Table3).3). Renal dysfunction was evidenced by a progressive increase in blood urea nitrogen and plasma creatinine concentrations as well as a decrease in urine output and creatinine clearance in placebo animals (Figure (Figure44 and Table Table3).3).