Early structural changes of the heart after experimental polytrauma and hemorrhagic shock

Abstract

Evidence is emerging that systemic inflammation after trauma drives structural and functional impairment of cardiomyocytes and leads to cardiac dysfunction, thus worsening the outcome of polytrauma patients. This study investigates the structural and molecular changes in heart tissue 4 h after multiple injuries with additional hemorrhagic shock using a clinically relevant rodent model of polytrauma. We determined mediators of systemic inflammation (keratinocyte chemoattractant, macrophage chemotactic protein 1), activated complement component C3a and cardiac troponin I in plasma and assessed histological specimen of the mouse heart via standard histomorphology and immunohistochemistry for cellular and subcellular damage and ongoing apoptosis. Further we investigated spatial and quantitative changes of connexin 43 by immunohistochemistry and western blotting. Our results show significantly increased plasma levels of both keratinocyte chemoattractant and cardiac troponin I 4 h after polytrauma and 2 h after induction of hypovolemia. Although we could not detect any morphological changes, immunohistochemical evaluation showed increased level of tissue high-mobility group box 1, which is both a damage-associated molecule and actively released as a danger response signal. Additionally, there was marked lateralization of the cardiac gap-junction protein connexin 43 following combined polytrauma and hemorrhagic shock. These results demonstrate a molecular manifestation of remote injury of cardiac muscle cells in the early phase after polytrauma and hemorrhagic shock with marked disruption of the cardiac gap junction. This disruption of an important component of the electrical conduction system of the heart may lead to arrhythmia and consequently to cardiac dysfunction.

Structural alterations and inflammation in the heart after multiple trauma followed by reamed versus non-reamed femoral nailing

“…The gap junction protein Cx43 was translocated from intercalated discs into the cytoplasm of the cardiomyocytes after multiple trauma in both parts of the left ventricle. This translocation of Cx43 was already demonstrated by our group in earlier studies after multiple trauma in pigs and mice [6,27], after blunt chest trauma in rats [16], after new-born asphyxia in pigs [28] and during chronic psychosocial stress in mice [29]. The endocytosis of Cx43 has been linked to alterations in the electromechanical communication of CMs and is therefore associated with are represented as white bars, 4 h after trauma as medium grey bars and 6 h after trauma as dark grey bars.…”

Traumatic injury pattern is of equal relevance as injury severity for experimental (poly)trauma modeling

“…While Weckbach et al . compared their experimental PT model consisting of a blunt chest trauma, head injury, femur fracture and soft tissue injury with different two-hit trauma models, and on the one hand has demonstrated that injury pattern does matter 23 , importantly, others underlined the not deniable relevance of HS after experimental PT on the other hand 24,25,42,43 . End organ damage in both murine PT and HS model demonstrate elevated transaminases after two or 24 h 31 .…”

Effects of Circulating HMGB-1 and Histones on Cardiomyocytes–Hemadsorption of These DAMPs as Therapeutic Strategy after Multiple Trauma

“…In traumatized patients, enhanced levels of circulating histones were correlated with the Sequential Organ Failure Assessment score, endothelial damage and the activation of the coagulation system [8]. In experimental blunt chest trauma in rats and in experimental multiple trauma in pigs and mice, we observed a systemic release of extracellular histones [3][4][5].…”

“…Post-traumatic cardiac injury can be caused by mechanical forces on the heart, particularly in the case of blunt chest trauma [3][4][5] or by inflammation, which mediates secondary cardiac damage. Severe trauma often leads to a systemic inflammatory response, accompanied by the release of danger associated molecular patterns (DAMPs), such as the high mobility group box-1 protein (HMGB-1) and extracellular histones.…”