INTESTINAL DAMAGE AND IMMUNE RESPONSE AFTER EXPERIMENTAL BLUNT ABDOMINAL TRAUMA.

ABSTRACT: Abdominal trauma (AT) is of major global importance, particularly because the civil, terroristic, and military traumatic potential of blast injuries has increased. The consequences of blunt abdominal injuries are highly variable and frequently underestimated or even overlooked. However, the underlying path mechanisms and subsequent innate immune response remain poorly understood. Therefore, we investigated the spatiotemporal local and systemic effects of a standardized blast-induced blunt AT on the intestine and innate immune response. In an established AT model, 66 male C57Bl6 mice were anesthetized and exposed to either a single blast wave centered on the epigastrium or control treatment (sham). At 2, 6, or 24 hours after trauma induction, animals were sacrificed. In 16 of 44 (36%) AT animals, one or more macroscopically visible injuries of the intestine were observed. Epithelial damage was detected by histological analysis of jejunum and ileum tissue samples, quantified by the Chiu score and by increased plasma concentrations of the intestinal fatty acid-binding protein, an enterocyte damage marker. Moreover, in the early posttraumatic period, elevated syndecan-1, claudin-5, and mucin-2 plasma levels also indicated alterations in the gut-blood barrier. Increased levels of pro-inflammatory cytokines such as TNF and macrophage inflammatory protein 2 in tissue homogenates and plasma indicate a systemic immune activation after blunt AT. In conclusion, we detected early morphological intestinal damage associated with high, early detectable intestinal fatty acid-binding protein plasma levels, and a considerable time- and dose-dependent impairment of the gut-blood barrier in a newly established mouse model of blunt AT. It appears to be a sufficient model for further studies of the intestinal immunopathophysiological consequences of AT and the evaluation of novel therapeutic approaches.

Temporal-spatial organ response after blast-induced experimental blunt abdominal trauma.

Abdominal trauma (AT) is of major global importance, particularly with the increased potential for civil, terroristic, and military trauma. The injury pattern and systemic consequences of blunt abdominal injuries are highly variable and frequently underestimated or even missed, and the pathomechanisms remain still poorly understood. Therefore, we investigated the temporal-spatial organ and immune response after a standardized blast-induced blunt AT. Anesthetized mice were exposed to a single blast wave centered on the epigastrium. At 2, 6, or 24 h after trauma, abdominal organ damage was assessed macroscopically, microscopically, and biochemically. A higher degree of trauma severity, determined by a reduction of the distance between the epigastrium and blast inductor, was reflected by a reduced survival rate. The hemodynamic monitoring during the first 120 min after AT revealed a decline in the mean arterial pressure within the first 80 min, whereas the heart rate remained quite stable. AT induced a systemic damage and inflammatory response, evidenced by elevated HMGB-1 and IL-6 plasma levels. The macroscopic injury pattern of the abdominal organs (while complex) was consistent, with the following frequency: liver > pancreas > spleen > left kidney > intestine > right kidney > others > lungs and was reflected by microscopic liver and pancreas damages. Plasma levels of organ dysfunction markers increased during the first 6 h after AT and subsequently declined, indicating an early, temporal impairment of the function on a multi-organ level. The established highly reproducible murine blunt AT, with time- and trauma-severity-dependent organ injury patterns, systemic inflammatory response, and impairment of various organ functions, reflects characteristics of human AT. In the future, this model may help to study the complex immuno-pathophysiological consequences and innovative therapeutic approaches after blunt AT.