Myocardial alterations following traumatic hemorrhagic injury.

Abstract

Cardiac dysfunction (CD) has emerged as a key contributor to delayed organ failure and late mortality in patients surviving the initial traumatic hemorrhagic response. Inflammatory processes are implicated in the initial stages of this CD; however, downstream pathways leading to a characteristic rapid fall in stroke volume and cardiac output are not yet fully defined. Currently, no cardioprotective treatments are available. We investigated the role of myocardial oxidative stress in the pathogenesis of CD associated to traumatic hemorrhagic injury, and its related metabolomic profile. Ex vivo tissue from a 3-hour murine model of pressure-controlled trauma hemorrhagic shock (THS) was analyzed. Animals were randomized to echocardiography-guided crystalloid fluid resuscitation or a control group (sham: cannulation and anesthesia only, or naïve: no intervention). Trauma hemorrhagic shock and naïve samples were assessed by immunohistochemistry for nuclear 8-hydroxy-2'-deoxyguanosine expression as a marker of oxidative stress. Metabolomic analysis of THS and sham group tissue was performed by LC-MS. 8-Hydroxy-2'-deoxyguanosine expression across the myocardium was significantly higher following THS injury compared to naïve group (33.01 ± 14.40% vs. 15.08 ± 3.96%, p < 0.05). Trauma hemorrhagic shock injury significantly increased lysine ( p = 0.022), and decreased aconitate ( p = 0.016) and glutamate ( p = 0.047) in the myocardium, indicating activation of a catabolic metabolism and oxidative stress response. We confirm the acute development of oxidative stress lesions and altered cardiac energy metabolism following traumatic hemorrhage injury, providing insight into the relationship between inflammatory damage and impaired cardiac contractility. These findings may provide targets for development of novel cardioprotective therapeutics aiming to decrease late mortality from trauma.