Angiotensin II in septic shock: effects on tissue perfusion, organ function, and mitochondrial respiration in a porcine model of fecal peritonitis.

Corrêa, Thiago D; Jeger, Victor; Pereira, Adriano José; Takala, Jukka; Djafarzadeh, Siamak; Jakob, Stephan M

OBJECTIVES To compare effects of norepinephrine and angiotensin II in experimental sepsis on hemodynamics, organ function, and mitochondrial respiration. DESIGN Randomized, controlled, study. SETTING University experimental laboratory. SUBJECTS Twenty-eight anesthetized, mechanically ventilated pigs. INTERVENTIONS Sixteen pigs were randomized to receive after 12 hours of fecal peritonitis fluid resuscitation and either norepinephrine (group NE; n = 8) or angiotensin II (group AT-II; n = 8) for 48 hours. A separate group (n = 8), treated with enalapril for 1 week before peritonitis and until study end, received fluids and norepinephrine (group E). The blood pressure dose-response to angiotensin II was evaluated in additional four nonseptic pigs. MEASUREMENTS AND MAIN RESULTS Blood pressure target (75-85 mm Hg) was reached in both NE and AT-II, and cardiac output increased similarly (NE: from 64 mL/kg/min [60-79 mL/kg/min] to 139 mL/kg/min [126-157 mL/kg/min]; AT-II from 79 mL/kg/min [65-86 mL/kg/min] to 145 mL/kg/min [126-147 mL/kg/min]; median, interquartile range). Renal plasma flow, prevalence of acute kidney injury, inflammation and coagulation patterns, and mitochondrial respiration did not differ between NE and AT-II. In group E, blood pressure targets were not achieved (mean arterial pressure at study end: NE: 81 mm Hg [76-85 mm Hg]; AT-II: 80 mm Hg [77-84 mm Hg]; E: 53 mm Hg [49-66 mm Hg], p = 0.002, compared to NE), whereas skeletal muscle adenosine triphosphate concentrations were increased. During resuscitation one animal died in groups AT-II and E. CONCLUSIONS Angiotensin II reversed sepsis-induced hypotension with systemic and regional hemodynamic effects similar to those of norepinephrine. Inhibition of angiotensin-converting enzyme before sepsis worsened the hypotension but enhanced skeletal muscle adenosine triphosphate. Modifying the renin-angiotensin system in sepsis should be further evaluated.