Focal intra-colon cooling reduces organ injury and systemic inflammation after REBOA management of lethal hemorrhage in rats

Awadhesh K Arya,Bingren Hu,Kurt Hu,Tieluo Li,Lalita Subedi

doi:10.1038/s41598-021-93064-4

Abstract

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a lifesaving maneuver for the management of lethal torso hemorrhage. However, its prolonged use leads to distal organ ischemia–reperfusion injury (IRI) and systemic inflammatory response syndrome (SIRS). The objective of this study is to investigate the blood-based biomarkers of IRI and SIRS and the efficacy of direct intestinal cooling in the prevention of IRI and SIRS. A rat lethal hemorrhage model was produced by bleeding 50% of the total blood volume. A balloon catheter was inserted into the aorta for the implementation of REBOA. A novel TransRectal Intra-Colon (TRIC) device was placed in the descending colon and activated from 10 min after the bleeding to maintain the intra-colon temperature at 37 °C (TRIC37°C group) or 12 °C (TRIC12°C group) for 270 min. The upper body temperature was maintained at as close to 37 °C as possible in both groups. Blood samples were collected before hemorrhage and after REBOA. The organ injury biomarkers and inflammatory cytokines were evaluated by ELISA method. Blood based organ injury biomarkers (endotoxin, creatinine, AST, FABP1/L-FABP, cardiac troponin I, and FABP2/I-FABP) were all drastically increased in TRIC37°C group after REBOA. TRIC12°C significantly downregulated these increased organ injury biomarkers. Plasma levels of pro-inflammatory cytokines TNF-α, IL-1b, and IL-17F were also drastically increased in TRIC37°C group after REBOA. TRIC12°C significantly downregulated the pro-inflammatory cytokines. In contrast, TRIC12°C significantly upregulated the levels of anti-inflammatory cytokines IL-4 and IL-10 after REBOA. Amazingly, the mortality rate was 100% in TRIC37°C group whereas 0% in TRIC12°C group after REBOA. Directly cooling the intestine offered exceptional protection of the abdominal organs from IRI and SIRS, switched from a harmful pro-inflammatory to a reparative anti-inflammatory response, and mitigated mortality in the rat model of REBOA management of lethal hemorrhage.

Highlights

IntroductionResuscitative endovascular balloon occlusion of the aorta, or REBOA, is a technique to manage torso h emorrhage[2,3,4]
Noncompressible torso hemorrhage carries a high mortality rate[1]
Our pilot study showed that the TRIC12°C offered virtually 100% survival rate while TRIC37°C resulted in 100% mortality in the rat model after 20–25 min Resuscitative endovascular balloon occlusion of the aorta (REBOA) management of lethal hemorrhage

Summary

Introduction

Resuscitative endovascular balloon occlusion of the aorta, or REBOA, is a technique to manage torso h emorrhage[2,3,4] This technique utilizes an occlusive balloon catheter inserted via the femoral artery into the descending aorta proximal to the injury site. Developing monitoring tools for abdominal organ IRI and therapies to prolong intestinal tissue tolerance to ischemia may be crucial to improving the clinical utility of REBOA. Severe intestinal IRI is often followed by a systemic inflammatory response, known as systemic. The objectives of this study were to investigate whether blood-based biomarkers can be used to indicate the IRI and SIRS and whether direct intestinal cooling can mitigate this damage in the rat model of REBOA management of lethal hemorrhage

Objectives

Results

Conclusion