Angiotensin II in Septic Shock: Effects on Tissue Perfusion, Organ Function, and Mitochondrial Respiration in a Porcine Model of Fecal Peritonitis

被引:64
作者
Correa, Thiago D. [1 ,2 ]
Jeger, Victor [1 ,2 ,3 ]
Pereira, Adriano Jose [1 ,2 ]
Takala, Jukka [1 ,2 ]
Djafarzadeh, Siamak [1 ,2 ]
Jakob, Stephan M. [1 ,2 ]
机构
[1] Univ Hosp Bern, Inselspital, Dept Intens Care Med, CH-3010 Bern, Switzerland
[2] Univ Bern, Bern, Switzerland
[3] Univ Bern, Grad Sch Cellular & Biomed Sci, Bern, Switzerland
基金
瑞士国家科学基金会; 巴西圣保罗研究基金会;
关键词
angiotensin II; enalapril; mitochondrial respiration; multiple organ failure; norepinephrine; septic shock; ACUTE-RENAL-FAILURE; NOREPINEPHRINE; ENALAPRIL; CATECHOLAMINES; DYSFUNCTION; METABOLISM; INCREASE; DISEASE; SYSTEM;
D O I
10.1097/CCM.0000000000000397
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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 norepineph-rine (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.
引用
收藏
页码:E550 / E559
页数:10
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