Introduction
Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a resuscitation tool for noncompressible hemorrhage, preserving perfusion to the heart and brain while interrupting life-threatening blood losses. However, patients often suffer ischemia-reperfusion injury after balloon deflation. We previously demonstrated that the protein GJA1-20k protects the mitochondria and reduces serum interleukin-6 (IL-6), an inflammatory marker linked with trauma severity and mortality. This study investigated whether GJA1-20k reduced IL-6 expression in the renal medulla and liver.
Methods
Twelve Yorkshire pigs were subjected to hemorrhagic shock by removing 25% of their blood volume, followed by 45 minutes of complete supra-coeliac REBOA. At 25 minutes, animals received an infusion of 0.9% saline (placebo) or GJA1-20k (0.01 mg/kg). Animals were transfused with autologous blood; the balloon catheter was deflated. Pigs received resuscitation with crystalloids and norepinephrine for MAP > 65 mmHg. Renal medulla and liver samples were obtained. The mRNA and protein IL-6 expression were quantified by reverse transcription polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC), respectively.
Results
RT-qPCR and IHC analyses revealed no difference in liver expression of IL-6. RT-qPCR revealed lower levels of renal medullary expression of IL-6 in the treatment group compared to the control group (Control: 0.51 [0.33–0.69]; GJA1-20k: 0.16 [0.12–0.3] IL-6 mRNA fold change) (p = 0.0140). IHC showed lower fluorescence in the renal medulla of animals in the treated group, compared to controls (Control: 126.76 [114.57–150.69]; GJA1-20k: 96.61 [94.14–121.95] mean fluorescence) (p = 0.0262).
Conclusions
Animals treated with GJA1-20k had lower levels of IL-6 production in the renal medulla, not the liver.
Previous publication: Manuscript in Critical Care Medicine
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GJA1-20K Reduces Levels of Interleukin-6 in Pigs with REBOA-Induced Ischemia-Reperfusion Injury by Taryn Hunt-Smith, Russell Johnson, BS, Jurgen Themen, MSc, Warda Mohamed, Gianni Lacey-Howard, BS, Scott Youngquist, MD, MS, Austin Johnson, MD, PhD, FACEP, Robin Shaw, MD, PhD & Guillaume Hoareau, DVM, PhD, FCCM, DACVECC, DECVECC