title: Angiotensin II in septic shock: effects on tissue perfusion, organ function, and mitochondrial respiration in a porcine model of fecal peritonitis.
abstract: OBJECTIVE
  To compare effects of norepinephrine and angiotensin II in experimental sepsis on hemodynamics, organ function, and mitochondrial respiration.
  
  
  METHODS
  Randomized, controlled, study.
  
  
  METHODS
  University experimental laboratory.
  
  
  METHODS
  Twenty-eight anesthetized, mechanically ventilated pigs.
  
  
  METHODS
  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.
  
  
  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.
authors.affiliation: 1Department of Intensive Care Medicine, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland. 2Graduate School for Cellular and Biomedical Sciences, University of Bern, Switzerland.
authors.forename: Thiago D
authors.initials: TD
authors.lastname: Corrêa
authors.forename: Victor
authors.initials: V
authors.lastname: Jeger
authors.forename: Adriano José
authors.initials: AJ
authors.lastname: Pereira
authors.forename: Jukka
authors.initials: J
authors.lastname: Takala
authors.forename: Siamak
authors.initials: S
authors.lastname: Djafarzadeh
authors.forename: Stephan M
authors.initials: SM
authors.lastname: Jakob
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D019069:Cell Respiration / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005440:Fluid Therapy; D006439:Hemodynamics / Q000187:drug effects; D007022:Hypotension / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008928:Mitochondria / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D010538:Peritonitis / Q000150:complications*; D011897:Random Allocation; D012084:Renin-Angiotensin System / Q000187:drug effects; D012772:Shock, Septic / Q000188:drug therapy* / Q000209:etiology; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009638:Norepinephrine