When trauma hits the heart: Divergent ventricular responses at histological and molecular levels in pigs

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BACKGROUND: Cardiac damage after polytrauma (PT) is associated with increased mortality. The aim of the present study was to investigate histopathological and transcriptomic changes in the right (RV) and left ventricle (LV) following PT. METHODS: A porcine PT model was conducted in an ICU setting with a follow-up period of 72 h. The animals were allocated into three groups: Sham, minor multiple trauma MiMT (femur fracture and blunt chest trauma) and major multiple trauma MaMT (MiMT with a pressure-controlled hemorrhagic shock). Cardiac damage was assessed via plasma levels of Troponin I and NT-proANP. Histomorphological damage was evaluated according to Heart Injury Score, immunohistochemistry for C5aR1, Nitrotyrosine, Caspase 3 and Connexin 43. mRNA/miRNA expression profiles were identified via NGS. RESULTS: TnI concentrations were elevated in MiMT and MaMT. Histological analyses of the LV revealed increased Nitrotyrosine in MiMT and C5aR1 in MaMT, whereas in the RV, no significant changes were detected. Differentially expressed mRNAs were mainly associated with cell death pathways (MiMT vs. MaMT) in the right ventricle, whereas in the LV, they were predominantly associated with cell death (MiMT vs. MaMT), antigen presentation, chemokine (MaMT vs. Sham), and cytokine signaling (MiMT vs. Sham). miRNA profiles differed strongly between ventricles, with extensive miRNA alterations in the LV (267 MiMT vs. Sham; 261 MaMT vs. Sham) and minimal changes in the RV (2 and 9, respectively). CONCLUSION: The study reveals distinct ventricular responses to PT, with the LV showing pronounced histopathological, mRNA/miRNA alterations, whereas the RV showed only minimal reaction to trauma.

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