TY  - JOUR
AB  - 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.
AU  - Rehberg, Sebastian
AU  - Yamamoto, Yusuke
AU  - Bartha, Eva
AU  - Sousse, Linda E.
AU  - Jonkam, Collette
AU  - Zhu, Yong
AU  - Traber, Lillian D.
AU  - Cox, Robert A.
AU  - Traber, Daniel L.
AU  - Enkhbaatar, Perenlei
DA  - 2013-05-11
DO  - 10.1186/cc12712
KW  - capillary leakage
KW  - cardiovascular hemodynamics
KW  - mitogen-activated protein kinase
KW  - myocardial oxygen consumption
KW  - tumor necrosis factor
KW  - left ventricular dysfunction
LA  - eng
N1  - Finanziert durch den Open-Access-Publikationsfonds 2013/2014 der Deutschen Forschungsgemeinschaft (DFG) und der Westfälischen Wilhelms-Universität Münster (WWU Münster).
N1  - Critical Care 17 (2013) R86
PY  - 2013-05-11
TI  - Antithrombin attenuates myocardial dysfunction and reverses systemic fluid accumulation following burn and smoke inhalation injury: a randomized, controlled, experimental study
UR  - https://nbn-resolving.org/urn:nbn:de:hbz:6-24319504882
Y2  - 2024-11-22T03:48:39
ER  -