Cardiovascular Dysfunction and the ATP-Adenosine Axis in Trauma

Abstract

Introduction Trauma is a significant contributor to global mortality and morbidity. Outcomes have improved over the last several decades, but there are still a population of patients who die after surviving their initial injuries. The cardiovascular system is vulnerable to the effects of both shock and inflammation but has not been adequately investigated. The purines ATP and adenosine have critical roles in metabolism, immunity, and the regulation of the cardiovascular system and may be pivotal in understanding why patients still die. Methods A retrospective analysis was used to describe the population with cardiovascular dysfunction. A prospective study design was used in the measurement of ATP and adenosine. Proteomic analysis was performed on samples from a prospectively maintained trauma biobank. Results Cardiovascular dysfunction was the dominant organ system to develop dysfunction following trauma and occurred in one third of trauma patients admitted to critical care. It was associated with a significant mortality and was manifest early in the disease process. ATP was associated with organ dysfunction; however, adenosine did not show any relationship to clinical outcome in this study. Proteomic analysis identified three distinct proteins that were upregulated in CVD; K2013, ATPase WRNIP1, and heat shock 70 kDa protein. K2013 has not yet been characterised and may be a novel biomarker of cardiovascular pathology. The role of heat shock 70 kDa protein in cardiovascular pathology has been documented in other pathologies, but this the first time it has been associated with cardiovascular dysfunction in trauma. 5 Conclusion Cardiovascular dysfunction is a phenotype of organ dysfunction that has not been fully described in the literature. It is associated with poor clinical outcomes, and can be predicted early. The ATP-adenosine axis did not influence the development of cardiovascular dysfunction. There was a distinct pattern of protein upregulation that differentiated patients who developed cardiovascular dysfunction.