Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a lifesaving intervention for major truncal hemorrhage. Balloon-tipped arterial catheters are inserted via the femoral artery to create a temporary occlusion of the aorta, which minimizes the rate of internal bleeding until definitive surgery can be conducted. There is growing concern over the resultant hypoperfusion and potential damage to tissues and organs downstream of REBOA. To better understand the acute hemodynamic changes imposed by REBOA, we developed a three-dimensional computational fluid dynamic (CFD) model under normal, hemorrhage, and aortic occlusion conditions. The goal was to characterize the acute hemodynamic changes and identify regions within the aortic vascular tree susceptible to abnormal flow and shear stress.Methods: Hemodynamic data from established porcine hemorrhage models were used to build a CFD model. Swine underwent 20% controlled hemorrhage and were randomized to receive a full or partial aortic occlusion. Using CT scans, we generated a pig-specific aortic geometry and imposed physiologically relevant inlet flow and outlet pressure boundary conditions to match in vivo data. By assuming non-Newtonian fluid properties, pressure, velocity, and shear stresses were quantified over a cardiac cycle.Results: We observed a significant rise in blood pressure (∼147 mmHg) proximal to REBOA, which resulted in increased flow and shear stress within the ascending aorta. Specifically, we observed high levels of shear stress within the subclavian arteries (22.75 Pa). Alternatively, at the site of full REBOA, wall shear stress was low (0.04 ± 9.07E-4 Pa), but flow oscillations were high (oscillatory shear index of 0.31). Comparatively, partial REBOA elevated shear levels to 84.14 ± 19.50 Pa and reduced flow oscillations. Our numerical simulations were congruent within 5% of averaged porcine experimental data over a cardiac cycle.Conclusion: This CFD model is the first to our knowledge to quantify the acute hemodynamic changes imposed by REBOA. We identified areas of low shear stress near the site of occlusion and high shear stress in the subclavian arteries. Future studies are needed to determine the optimal design parameters of endovascular hemorrhage control devices that can minimize flow perturbations and areas of high shear.

Background We sought to determine the magnitude of the inherent inter-animal physiologic variability by automating a porcine Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) protocol to minimize external influences that might alter physiology and confound experimental results. Methods Swine (n = 42) underwent a controlled 30% blood volume hemorrhage followed by 30 minutes of REBOA (ie, ischemic phase). The animals were weaned from REBOA autonomously over 15 minutes, beginning the reperfusion phase, while continuing to provide partial flow balloon support to maintain a target proximal mean arterial pressure (pMAP) of 65 mmHg. Simultaneously, shed blood was re-transfused as part of the resuscitation efforts. Physiologic data were continuously recorded, and serum samples were serially collected. Baseline characteristics, variance in vital signs, and 8-isoprostane levels were quantified during hemorrhage, REBOA, and reperfusion phases. Results There was no significant difference in baseline physiology across animals ( P > .05). Hemodynamic variability was highest for pMAP during the ischemic phase ( P = .001) and for distal mean arterial pressure (dMAP) during the weaning/reperfusion phase ( P = .001). The latter finding indicated the variable physiologic response to ischemia-reperfusion injury, as the automated balloon support required by each animal to maintain pMAP was highly variable. Circulating 8-isoprostane variance was significantly higher following the start of reperfusion compared to baseline levels ( P = .001). Discussion Despite subjecting animals to a highly consistent ischemia-reperfusion injury through automation, we noted significant variability in the hemodynamic and biochemical response. These findings illustrate the inherent physiologic variability and potential limitations of porcine large animal models for the study of shock.

The Modern Western Diet has been associated with the rise in metabolic and inflammatory diseases, including obesity, diabetes, and cardiovascular disease. This has been attributed, in part, to the increase in dietary omega-6 polyunsaturated fatty acid (PUFA) consumption, specifically linoleic acid (LA), arachidonic acid (ARA), and their subsequent metabolism to pro-inflammatory metabolites which may be driving human disease. Conversion of dietary LA to ARA is regulated by genetic variants near and within the fatty acid desaturase (FADS) haplotype block, most notably single nucleotide polymorphism rs174537 is strongly associated with FADS1 activity and expression. This variant and others within high linkage disequilibrium may potentially explain the diversity in both diet and inflammatory mediators that drive chronic inflammatory disease in human populations. Mechanistic exploration into this phenomenon using human hepatocytes is limited by current two-dimensional culture models that poorly replicate in vivo functionality. Therefore, we aimed to develop and characterize a three-dimensional hepatic construct for the study of human PUFA metabolism. Primary human hepatocytes cultured in 3D hydrogels were characterized for their capacity to represent basic lipid processing functions, including lipid esterification, de novo lipogenesis, and cholesterol efflux. They were then exposed to control and LA-enriched media and reproducibly displayed allele-specific metabolic activity of FADS1, based on genotype at rs174537. Hepatocytes derived from individuals homozygous with the minor allele at rs174537 (i.e., TT) displayed the slowest metabolic conversion of LA to ARA and significantly reduced FADS1 and FADS2 expression. These results support the feasibility of using 3D human hepatic cultures for the study of human PUFA and lipid metabolism and relevant gene-diet interactions, thereby enabling future nutrition targets in humans.