Sublethal trauma model with systemic endotoxemia for the study of microcirculatory disorders after the second hit.
BACKGROUND
Experimental models often cannot simulate the clinical situation in traumatized patients where the septic second hit finally leads to multiple organ dysfunction syndrome and death. We present an experimental animal model combining initial standardized soft tissue trauma to the left hindlimb of rats with subsequent sublethal systemic endotoxemia.


METHODS
This study characterizes the influence of trauma and systemic endotoxemia on nutritive blood flow, inflammatory cell-cell interaction and tissue cell integrity in the traumatized region.


RESULTS
At 24 h after local tissue contusion, in vivo analysis of the skeletal muscle microcirculation by means of high resolution fluorescence microscopy revealed intravascular leukocyte accumulation and impairment of nutritive perfusion with tissue hypoxia. Moreover, muscle tissue damage was characterized by myocyte cell apoptosis. Additional systemic exposure of animals to E. coli lipopolysaccharide at 6 h after soft tissue contusion caused a drop in arterial blood pressure as well as coagulatory disorders, as given by marked thrombocytopenia and reduced thromboplastin times. In double-hit exposed animals, skeletal muscle microcirculation presented with an aggravation of inflammation, perfusion failure, and apoptotic cell death after 24 h.


CONCLUSIONS
This model more closely resembles the scenario of polytraumatized patients with the risk of secondary infections and, thus, is suited to characterize anti-inflammatory drugs with respect to their potential to interfere with microcirculatory disorders and elaboration of disseminated intravascular coagulation after trauma.
Gierer
Philip
P
Institute for Experimental Surgery, University of Rostock, Rostock, Germany.
Hoffmann
Johannes N
JN
Mahr
Felix
F
Menger
Michael D
MD
Mittlmeier
Thomas
T
Gradl
Georg
G
Vollmar
Brigitte
B
D000818:Animals; D001778:Blood Coagulation Disorders / Q000209:etiology; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000503:physiopathology*; D006439:Hemodynamics; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D008833:Microcirculation; D008856:Microscopy, Fluorescence; D018482:Muscle, Skeletal / Q000098:blood supply*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017695:Soft Tissue Injuries / Q000150:complications / Q000503:physiopathology*
D008070:Lipopolysaccharides