当前位置： SCI文献检索 > CRITICAL CARE期刊下所有文献 > Role of selective V2-receptor-antagonism in septic shock: a randomized, controlled, experimental study.

Role of selective V2-receptor-antagonism in septic shock: a randomized, controlled, experimental study.

Abstract：

INTRODUCTION:V(2)-receptor (V(2)R) stimulation potentially aggravates sepsis-induced vasodilation, fluid accumulation and microvascular thrombosis. Therefore, the present study was performed to determine the effects of a first-line therapy with the selective V(2)R-antagonist (Propionyl(1)-D-Tyr(Et)(2)-Val(4)-Abu(6)-Arg(8,9))-Vasopressin on cardiopulmonary hemodynamics and organ function vs. the mixed V(1a)R/V(2)R-agonist arginine vasopressin (AVP) or placebo in an established ovine model of septic shock. METHODS:After the onset of septic shock, chronically instrumented sheep were randomly assigned to receive first-line treatment with the selective V(2)R-antagonist (1 μg/kg per hour), AVP (0.05 μg/kg per hour), or normal saline (placebo, each n = 7). In all groups, open-label norepinephrine was additionally titrated up to 1 μg/kg per minute to maintain mean arterial pressure at 70 ± 5 mmHg, if necessary. RESULTS:Compared to AVP- and placebo-treated animals, the selective V(2)R-antagonist stabilized cardiopulmonary hemodynamics (mean arterial and pulmonary artery pressure, cardiac index) as effectively and increased intravascular volume as suggested by higher cardiac filling pressures. Furthermore, left ventricular stroke work index was higher in the V(2)R-antagonist group than in the AVP group. Notably, metabolic (pH, base excess, lactate concentrations), liver (transaminases, bilirubin) and renal (creatinine and blood urea nitrogen plasma levels, urinary output, creatinine clearance) dysfunctions were attenuated by the V(2)R-antagonist when compared with AVP and placebo. The onset of septic shock was associated with an increase in AVP plasma levels as compared to baseline in all groups. Whereas AVP plasma levels remained constant in the placebo group, infusion of AVP increased AVP plasma levels up to 149 ± 21 pg/mL. Notably, treatment with the selective V(2)R-antagonist led to a significant decrease of AVP plasma levels as compared to shock time (P < 0.001) and to both other groups (P < 0.05 vs. placebo; P < 0.001 vs. AVP). Immunohistochemical analyses of lung tissue revealed higher hemeoxygenase-1 (vs. placebo) and lower 3-nitrotyrosine concentrations (vs. AVP) in the V(2)R-antagonist group. In addition, the selective V(2)R-antagonist slightly prolonged survival (14 ± 1 hour) when compared to AVP (11 ± 1 hour, P = 0.007) and placebo (11 ± 1 hour, P = 0.025). CONCLUSIONS:Selective V(2)R-antagonism may represent an innovative therapeutic approach to attenuate multiple organ dysfunction in early septic shock.

journal_name

Crit Care

journal_title

Critical care (London, England)

authors

Rehberg S,Ertmer C,Lange M,Morelli A,Whorton E,Dünser M,Strohhäcker AK,Lipke E,Kampmeier TG,Van Aken H,Traber DL,Westphal M

doi

10.1186/cc9320

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

R200

issue

eissn

1364-8535

issn

1466-609X

pii

cc9320

journal_volume

pub_type

杂志文章,随机对照试验

在线工具

Role of selective V2-receptor-antagonism in septic shock: a randomized, controlled, experimental study.