Antithrombin attenuates myocardial dysfunction and reverses systemic fluid accumulation following burn and smoke inhalation injury: a randomized, controlled, experimental study

Critical Care

Perenlei Enkhbaatar¹  Daniel L Traber¹  Robert A Cox¹  Lillian D Traber³  Yong Zhu³  Collette Jonkam³  Linda E Sousse³  Eva Bartha³  Yusuke Yamamoto³  Sebastian Rehberg² 

[1] Shriners Hospital for Children, 815 Avenue D, Galveston, TX 77550, USA;Department of Anaesthesiology and Intensive Care, University of Muenster, Albert-Schweitzer-Campus 1, 48149 Muenster, Germany;Investigational Intensive Care Unit, Department of Anesthesiology, The University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555, USA

关键词: left ventricular dysfunction;    tumor necrosis factor;    myocardial oxygen consumption;    mitogen-activated protein kinase;    cardiovascular hemodynamics;    capillary leakage;   

Others  :  818154
DOI  :  10.1186/cc12712

 received in 2013-01-28, accepted in 2013-05-11,  发布年份 2013

【 摘 要 】

Introduction

We hypothesized that maintaining physiological plasma levels of antithrombin attenuates myocardial dysfunction and inflammation as well as vascular leakage associated with burn and smoke inhalation injury. Therefore, the present prospective, randomized experiment was conducted using an established ovine model.

Methods

Following 40% of total body surface area, third degree flame burn and 4 × 12 breaths of cold cotton smoke, chronically instrumented sheep were randomly assigned to receive an intravenous infusion of 6 IU/kg/h recombinant human antithrombin (rhAT) or normal saline (control group; n = 6 each). In addition, six sheep were designated as sham animals (not injured, continuous infusion of vehicle). During the 48 h study period the animals were awake, mechanically ventilated and fluid resuscitated according to standard formulas.

Results

Compared to the sham group, myocardial contractility was severely impaired in control animals, as suggested by lower stroke volume and left ventricular stroke work indexes. As a compensatory mechanism, heart rate increased, thereby increasing myocardial oxygen consumption. In parallel, myocardial inflammation was induced via nitric oxide production, neutrophil accumulation (myeloperoxidase activity) and activation of the p38-mitogen-activated protein kinase pathway resulting in cytokine release (tumor necrosis factor-alpha, interleukin-6) in control vs. sham animals. rhAT-treatment significantly attenuated these inflammatory changes leading to a myocardial contractility and myocardial oxygen consumption comparable to sham animals. In control animals, systemic fluid accumulation progressively increased over time resulting in a cumulative positive fluid balance of about 4,000 ml at the end of the study period. Contrarily, in rhAT-treated animals there was only an initial fluid accumulation until 24 h that was reversed back to the level of sham animals during the second day.

Conclusions

Based on these findings, the supplementation of rhAT may represent a valuable therapeutic approach for cardiovascular dysfunction and inflammation after burn and smoke inhalation injury.

【 授权许可】

   
2013 Rehberg et al.; licensee BioMed Central Ltd.

【 图 表 】

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