Cardiac Depression in Pigs after Multiple Trauma \u2013 Characterization of Posttraumatic Structural and Functional Alterations

Miriam Kalbitz ,Philipp Störmann ,Helmut Hummler ,Birte Weber ,Klemens Horst ,Hans-Christian Pape ,Roman Pfeifer ,Florian Gebhard ,Tim Philipp Simon ,Stephan Schwarz ,Jochen Preßmar ,Belinda Bosch ,Christian Braun ,Markus Huber‐Lang ,Felix M Hoenes ,Frank Hildebrand

doi:10.1038/s41598-017-18088-1

Abstract

The purpose of this study was to define the relationship between cardiac depression and morphological and immunological alterations in cardiac tissue after multiple trauma. However, the mechanistic basis of depressed cardiac function after trauma is still elusive. In a porcine polytrauma model including blunt chest trauma, liver laceration, femur fracture and haemorrhage serial trans-thoracic echocardiography was performed and correlated with cellular cardiac injury as well as with the occurrence of extracellular histones in serum. Postmortem analysis of heart tissue was performed 72 h after trauma. Ejection fraction and shortening fraction of the left ventricle were significantly impaired between 4 and 27 h after trauma. H-FABP, troponin I and extracellular histones were elevated early after trauma and returned to baseline after 24 and 48 h, respectively. Furthermore, increased nitrotyrosine and Il-1β generation and apoptosis were identified in cardiac tissue after trauma. Main structural findings revealed alteration of connexin 43 (Cx43) and co-translocation of Cx43 and zonula occludens 1 to the cytosol, reduction of α-actinin and increase of desmin in cardiomyocytes after trauma. The cellular and subcellular events demonstrated in this report may for the first time explain molecular mechanisms associated with cardiac dysfunction after multiple trauma.

Highlights

Pathophysiological effects of blunt cardiac injury such as firmness of cardiac tissue was found in a pig model of blunt chest trauma[10]
Extracellular histone concentration in serum was elevated 1.5, 3 and 5.5 h after trauma compared to baseline in both treatment groups damage control orthopaedics (DCO) and early total care (ETC) and 1.5, 5.5 and 24 h compared to sham procedure
H-FABP serum concentration was elevated as early as 1.5 h after trauma and after 3 and 5.5 h compared to sham procedure and 1.5 h and 3 h compared to baseline after trauma in both treatment groups (DCO and ETC) and after 24 h in ETC treatment group compared to baseline

Summary

Introduction

Pathophysiological effects of blunt cardiac injury such as firmness of cardiac tissue was found in a pig model of blunt chest trauma[10]. DAMPs such as circulating nucleosomes have been reported to correlate with the injury severity score in humans and were broken down into individual histones[18], interacting with a variety of cells including cardiomyocytes presumably via toll like receptors[19]. After multiple trauma patients faces a second hit, for example surgical intervention, which in the state of vulnerable condition is associated with hyperinflammation and multiple organ dysfunction (MODS). In the present study a large animal model of polytrauma in pigs including blunt chest trauma, femur fracture, liver laceration followed by pressure-controlled haemorrhage was applied to investigate morphological, immunological and functional changes of cardiac injury early after multiple trauma

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Conclusion