Cardiac damage after experimental blunt chest trauma and multiple trauma with hemorrhagic shock

Abstract

Abstract INTRODUCTION Heart injury represents an independent predictor for a poor outcome after trauma. However, molecular mechanisms of depressed cardiac function after trauma remains elusive. METHODS Multiple trauma (PTHS) included a blast-wave induced blunt chest trauma, traumatic brain injury and closed femoral fracture as well as pressure controlled hemorrhagic shock. In vitro studies were performed using human cardiomyocytes (Cellular Dynamics). Data were analyzed by one-way ANOVA analysis of variance followed by Dunnett’s multiple comparison test. RESULTS 4h after PTHS in mice plasma concentration of pro-inflammatory cytokines such as MCP-1 and chemokine KC were significantly increased in comparison to sham treated animals. Plasma concentration of cardiac troponin levels were significantly increased early after experimental PTHS. HMGB1 staining provided significant increase in left ventricular tissue after PTHS. Distribution of the gap junction protein connexin 43 (Cx43) was was disintegrated in histological sections. In presence of TNF reactive oxygen species were significantly increased in human cardiomyocytes, indicating a redox imbalance indicative of an oxidative state. Furthermore, presence of TNF in cultured human cardiomyocytes was associated with increased expression of the NLRP3 inflammasome and increased concentration of troponin in supernatant, which is specific marker for cardiac cell damage. DISCUSSION The cellular and subcellular events demonstrated in this report may explain molecular mechanisms associated with cardiac dysfunction after trauma. Better understanding of cardiac damage and molecular mechanisms of cardiac dysfunction after trauma will improve patient care in future.