Resuscitative endovascular balloon occlusion of the aorta induced myocardial injury is mitigated by endovascular variable aortic control.

BACKGROUND: The cardiac effects of resuscitative endovascular balloon occlusion of the aorta (REBOA) are largely unknown. We hypothesized that increased afterload from REBOA would lead to cardiac injury, and that partial flow using endovascular variable aortic control (EVAC) would mitigate this injury. METHODS: Eighteen anesthetized swine underwent controlled 25% blood volume hemorrhage. Animals were randomized to either Zone 1 REBOA, Zone 1 EVAC, or no intervention (control) for 45 minutes. Animals were then resuscitated with shed blood, observed during critical care, and euthanized after a 6-hour total experimental time. Left ventricular function was measured with a pressure-volume catheter, and blood samples were drawn at routine intervals. RESULTS: The average cardiac output during the intervention period was higher in the REBOA group (9.3 [8.6-15.4] L/min) compared with the EVAC group (7.2 [5.8-8.0] L/min, p = 0.01) and the control group (6.8 [5.8-7.7] L/min, p < 0.01). At the end of the intervention, the preload recruitable stroke work was significantly higher in both the REBOA and EVAC groups compared with the control group (111.2 [102.5-148.6] and 116.7 [116.6-141.4] vs. 67.1 [62.7-87.9], p = 0.02 and p < 0.01, respectively). The higher preload recruitable stroke work was maintained throughout the experiment in the EVAC group, but not in the REBOA group. Serum troponin concentrations after 6 hours were higher in the REBOA group compared with both the EVAC and control groups (6.26 ± 5.35 ng/mL vs 0.92 ± 0.61 ng/mL and 0.65 ± 0.38 ng/mL, p = 0.05 and p = 0.03, respectively). Cardiac intramural hemorrhage was higher in the REBOA group compared with the control group (1.67 ± 0.46 vs. 0.17 ± 0.18, p = 0.03), but not between the EVAC and control groups. CONCLUSION: In a swine model of hemorrhagic shock, complete aortic occlusion resulted in cardiac injury, although there was no direct decrease in cardiac function. EVAC mitigated the cardiac injury and improved cardiac performance during resuscitation and critical care.

A novel model of highly lethal uncontrolled torso hemorrhage in swine.

INTRODUCTION: A reproducible, lethal noncompressible torso hemorrhage model is important to civilian and military trauma research. Current large animal models balancing clinical applicability with standardization and internal validity. As such, large animal models of trauma vary widely in the surgical literature, limiting comparisons. Our aim was to create and validate a porcine model of uncontrolled hemorrhage that maximizes reproducibility and standardization. METHODS: Seven Yorkshire-cross swine were anesthetized, instrumented, and splenectomized. A simple liver tourniquet was applied before injury to prevent unregulated hemorrhage while creating a traumatic amputation of 30% of the liver. Release of the tourniquet and rapid abdominal closure following injury provided a standardized reference point for the onset and duration of uncontrolled hemorrhage. At the moment of death, the liver tourniquet was quickly reapplied to provide accurate quantification of intra-abdominal blood loss. Weight and volume of the resected and residual liver segments were measured. Hemodynamic parameters were recorded continuously throughout each experiment. RESULTS: This liver injury was rapidly and universally lethal (11.2 ± 4.9 min). The volume of hemorrhage (35.8% ± 6% of total blood volume) and severity of uncontrolled hemorrhage (100% of animals deteriorated to a sustained mean arterial pressure <35 mmHg for 5 min) were consistent across all animals. Use of the tourniquet effectively halted preprocedure and postprocedure blood loss allowing for accurate quantification of amount of hemorrhage over a defined period. In addition, the tourniquet facilitated the creation of a consistent liver resection weight (0.0043 ± 0.0003 liver resection weight: body weight) and as a percentage of total liver resection weight (27% ± 2.2%). CONCLUSIONS: This novel tourniquet-assisted noncompressible torso hemorrhage model creates a standardized, reproducible, highly lethal, and clinically applicable injury in swine. Use of the tourniquet allowed for consistent liver injury and precise control over hemorrhage. Recorded blood loss was similar across all animals. Improving reproducibility and standardization has the potential to offer improvements in large animal translational models of hemorrhage. LEVEL OF EVIDENCE: Level I.

Automated variable aortic control versus complete aortic occlusion in a swine model of hemorrhage.

BACKGROUND: Future endovascular hemorrhage control devices will require features that mitigate the adverse effects of vessel occlusion. Permissive regional hypoperfusion (PRH) with variable aortic control (VAC) is a novel strategy to minimize hemorrhage and reduce the ischemic burden of complete aortic occlusion (AO). The objective of this study was to compare PRH with VAC to AO in a lethal model of hemorrhage. METHODS: Twenty-five swine underwent cannulation of the supraceliac aorta, with diversion of aortic flow through an automated extracorporeal circuit. After creation of uncontrolled liver hemorrhage, animals were randomized to 90 minutes of treatment: Control (full, unregulated flow; n = 5), AO (no flow; n = 10), and PRH with VAC (dynamic distal flow initiated after 20 minutes of AO; n = 10). In the PRH group, distal flow rates were regulated between 100 and 300 mL/min based on a desired, preset range of proximal mean arterial pressure (MAP). At 90 minutes, damage control surgery, resuscitation, and restoration of full flow ensued. Critical care continued for 4.5 hours or until death. Hemodynamic parameters and markers of ischemia were recorded. RESULTS: Study survival was 0%, 50%, and 90% for control, AO, and VAC, respectively (p < 0.01). During intervention, VAC resulted in more physiologic proximal MAP (84 ± 18 mm Hg vs. 105 ± 9 mm Hg, p < 0.01) and higher renal blood flow than AO animals (p = 0.02). During critical care, VAC resulted in higher proximal MAP (73 ± 8 mm Hg vs. 50 ± 6 mm Hg, p < 0.01), carotid and renal blood flow (p < 0.01), lactate clearance (p < 0.01), and urine output (p < 0.01) than AO despite requiring half the volume of crystalloids to maintain proximal MAP ≥50 mm Hg (p < 0.01). CONCLUSION: Permissive regional hypoperfusion with variable aortic control minimizes the adverse effects of distal ischemia, optimizes proximal pressure to the brain and heart, and prevents exsanguination in this model of lethal hemorrhage. These findings provide foundational knowledge for the continued development of this novel paradigm and inform next-generation endovascular designs.

Extending the golden hour: Partial resuscitative endovascular balloon occlusion of the aorta in a highly lethal swine liver injury model.

BACKGROUND: Combat-injured patients may require rapid and sustained support during transport; however, the prolonged aortic occlusion produced by conventional resuscitative endovascular balloon occlusion of the aorta (REBOA) may lead to substantial morbidity. Partial REBOA (P-REBOA) may permit longer periods of occlusion by allowing some degree of distal perfusion. However, the ability of this procedure to limit exsanguination is unclear. We evaluated the impact of P-REBOA on immediate survival and ongoing hemorrhage in a highly lethal swine liver injury model. METHODS: Fifteen Yorkshire-cross swine were anesthetized, instrumented, splenectomized, and subjected to rapid 10% total blood loss followed by 30% liver amputation. Coagulopathy was created through colloid hemodilution. Randomized swine received no intervention (control), P-REBOA, or complete REBOA (C-REBOA). Central mean arterial pressure (cMAP), carotid blood flow, and blood loss were recorded. Balloons remained inflated in the P-REBOA and C-REBOA groups for 90 minutes followed by graded deflation. The study ended at 180 minutes from onset of hemorrhage or death of the animal. Survival analysis was performed, and data were analyzed using repeated-measures analysis of variance with post hoc pairwise comparisons. RESULTS: Mean survival times in the control, P-REBOA, and C-REBOA groups were, 25 ± 21, 86 ± 40, and 163 ± 20 minutes, respectively (p < 0.001). Blood loss was greater in the P-REBOA group than the C-REBOA or control groups, but this difference was not significant (4,722 ± 224, 3,834 ± 319, 3,818 ± 37 mL, respectively, p = 0.10). P-REBOA resulted in maintenance of near-baseline carotid blood flow and cMAP, while C-REBOA generated extreme cMAP and prolonged supraphysiologic carotid blood flow. Both experimental groups experienced profound decreases in cMAP following balloon deflation. CONCLUSION: In the setting of severe ongoing hemorrhage, P-REBOA increased survival time beyond the golden hour while maintaining cMAP and carotid flow at physiologic levels.

Comparison of AlloDerm and AlloMax tissue incorporation in rats.

BACKGROUND: Human acellular dermal matrices (HADMs) are used in a variety of settings. AlloMax is a new HADM currently being used for breast reconstruction and hernia repair. We compared the in vivo tissue integration of AlloMax to AlloDerm, a well-studied HADM, in rats. METHODS: We implanted AlloDerm and AlloMax patches into subcutaneous pockets on the backs of 32 male Sprague-Dawley rats. The animals were killed after either 4 or 8 weeks, and the patches were recovered and stained for histopathologic analyses. Microscopic end points included patch thickness, vascularization, tissue in-growth, fibroblast proliferation, and inflammation. RESULTS: All animals completed the study without complications or infection. There were no significant differences in graft thicknesses at 4 and 8 weeks. Microscopically, at 4 weeks, AlloDerm sections had significantly more microvessels than AlloMax (P = 0.02). This disparity increased by 8 weeks (P < 0.01). Similarly, we found greater tissue in-growth and fibroblast proliferation in AlloDerm than AlloMax sections at 4 (P < 0.01) and at 8 (P < 0.01) weeks. Inflammatory infiltrates consisted of lymphocytes, histiocytes, eosinophils, and plasma cells. Deep graft infiltration by predominately lymphocytic inflammatory cells was significantly higher in AlloDerm than AlloMax grafts at 4 (P = 0.01) and 8 (P = 0.02) weeks. Graft necrosis was uncommon, but marginal fibrosis was similar in both. CONCLUSIONS: AlloDerm grafts had greater neovascularization, tissue infiltration, fibroblast proliferation, and inflammatory reaction than AlloMax grafts when placed subcutaneously in rats. AlloDerm may be better incorporated than AlloMax when placed in vivo.