The degree of aortic occlusion in the setting of trauma alters the extent of acute kidney injury associated with mitochondrial preservation.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is used to control noncompressible hemorrhage not addressed with traditional tourniquets. However, REBOA is associated with acute kidney injury (AKI) and subsequent mortality in severely injured trauma patients. Here, we investigated how the degree of aortic occlusion altered the extent of AKI in a porcine model. Female Yorkshire-cross swine (n = 16, 68.1 ± 0.7 kg) were anesthetized and had carotid and bilateral femoral arteries accessed for REBOA insertion and distal and proximal blood pressure monitoring. Through a laparotomy, a 6-cm liver laceration was performed and balloon inflation was performed in zone 1 of the aorta for 90 min, during which animals were randomized to target distal mean arterial pressures of 25 or 45 mmHg via balloon volume adjustment. Blood draws were taken at baseline, end of occlusion, and time of death, at which point renal tissues were harvested 6 h after balloon deflation for histological and molecular analyses. Renal blood flow was lower in the 25-mmHg group (48.5 ± 18.3 mL/min) than in the 45-mmHg group (177.9 ± 27.2 mL/min) during the occlusion phase, which recovered and was not different after balloon deflation. AKI was more severe in the 25-mmHg group, as evidenced by circulating creatinine, blood urea nitrogen, and urinary neutrophil gelatinase-associated lipocalin. The 25-mmHg group had increased tubular necrosis, lower renal citrate synthase activity, increased tissue and circulating syndecan-1, and elevated systemic inflammatory cytokines. The extent of renal ischemia-induced AKI is associated with the magnitude of mitochondrial biomass and systemic inflammation, highlighting potential mechanistic targets to combine with partial REBOA strategies to prevent AKI.NEW & NOTEWORTHY Large animal models of ischemia-reperfusion acute kidney injury (IR-AKI) are lacking. This report establishes a titratable IR-AKI model in swine in which a balloon catheter can be used to alter distal pressures experienced by the kidney, thus controlling renal blood flow. Lower blood flow results in greater renal dysfunction and structural damage, as well as lower mitochondrial biomass, elevated systemic inflammation, and vascular dysfunction.

Real-Time Measurements of Oral Mucosal Carbon Dioxide (POMCO2) Reveals an Inverse Correlation With Blood Pressure in a Porcine Model of Coagulopathic Junctional Hemorrhage.

INTRODUCTION: Shock states that occur during, for example, profound hemorrhage can cause global tissue hypoperfusion leading to organ failure. There is an unmet need for a reliable marker of tissue perfusion during hemorrhage that can be followed longitudinally. Herein, we investigated whether longitudinal POMCO2 tracks changes in hemodynamics in a swine model of coagulopathic uncontrolled junctional hemorrhage. MATERIALS AND METHODS: Female Yorkshire-crossbreed swine (n = 7, 68.1 ± 0.7 kg) were anesthetized and instrumented for continuous measurement of mean arterial pressure (MAP). Coagulopathy was induced by the exchange of 50 to 60% of blood volume with 6% Hetastarch over 30 minutes to target a hematocrit of <15%. A 4.5-mm arteriotomy was made in the right common femoral artery with 30 seconds of free bleeding. POMCO2 was continuously measured from baseline through hemodilution, hemorrhage, and a subsequent 3-h intensive care unit period. Rotational thromboelastometry and blood gases were measured. RESULTS: POMCO2 and MAP showed no significant changes during the hemodilution phase of the experiment, which produced coagulopathy evidenced by prolonged clot formation times. However, POMCO2 increased because of the uncontrolled hemorrhage by 11.3 ± 3.1 mmHg and was inversely correlated with the drop (17.9 ± 5.9 mmHg) in MAP (Y = -0.4122*X + 2.649, P = .02, r2 = 0.686). In contrast, lactate did not significantly correlate with the changes in MAP (P = .35) or POMCO2 (P = .37). CONCLUSIONS: Despite the logical appeal of measuring noninvasive tissue CO2 measurement as a surrogate for gastrointestinal perfusion, prior studies have only reported snapshots of this readout. The present investigation shows real-time longitudinal measurement of POMCO2 to confirm that MAP inversely correlates to POMCO2 in the face of coagulopathy. The simplicity of measuring POMCO2 in real time can provide an additional practical option for military or civilian medics to monitor trends in hypoperfusion during hemorrhagic shock.

Evaluation of novel hemostatic agents in a coagulopathic swine model of junctional hemorrhage.

BACKGROUND: Hemostatic dressings are used extensively in both military and civilian trauma to control lethal noncompressible hemorrhage. The ideal topical hemostatic agent would provide reliable hemostasis in patients with profound acidosis, coagulopathy, and shock. This study aimed to compare next-generation hemostatic agents against the current military standard in a translational swine model of vascular injury and coagulopathy. METHODS: Female Yorkshire swine were randomized to eight groups (total n = 63; control n = 14, per group n = 7) of hemostatic agents and included: QuikClot Combat Gauze (Teleflex, Morrisville, NC), which served as the control; BloodSTOP IX (LifeScience Plus, Mountain View, CA); Celox Rapid (Medtrade Product, Crewe, United Kingdom); ChitoSAM 100 (Sam Medical, Tualatin, OR); EVARREST Fibrin Sealant Patch (Ethicon, Raritan, NJ); TAC Wrapping Gauze (H&H Medical, Williamsburg, VA); ChitoGauze XR Pro (Tricol Biomedical, Portland, OR); and X-Stat 30 (RevMedX, Wilsonville, OR). Hemodilution via exchange transfusion of 6% hetastarch was performed to induce acidosis and coagulopathy. An arteriotomy was created, allowing 30 seconds of free bleeding followed by application of the hemostatic agent and compression via an external compression device. A total of three applications were allowed for continued/recurrent bleeding. All blood loss was collected, and hemostatic agents were weighed to calculate blood volume loss. Following a 180-minute observation period, angiography was completed to evaluate for technical complication and distal perfusion of the limb. Finally, the limb was ranged five times to assess for rebleeding and clot stability. RESULTS: All swine were confirmed coagulopathic with rotational thromboelastography and acidotic (pH 7.2 ± 0.02). BloodSTOP IX allowed a significant increase in blood loss and number of applications required to obtain hemostasis compared with all other groups. BloodSTOP IX demonstrated a decreased survival rate (29%, p = 0.02). All mortalities were directly attributed to exsanguination as a result of device failure. In surviving animals, there was no difference in extravasation. BloodSTOP IX had an increased rebleeding rate after ranging compared with QuikClot Combat Gauze ( p = 0.007). CONCLUSION: Most novel hemostatic agents demonstrated comparable efficacy compared with the currently military standard hemostatic dressing, CG.

Invasive mechanical ventilation using a bilevel PAP ST device in a healthy swine model.

PURPOSE: The Coronavirus Disease 2019 (COVID-19) pandemic may cause an acute shortage of ventilators. Standard noninvasive bilevel positive airway pressure devices with spontaneous and timed respirations (bilevel PAP ST) could provide invasive ventilation but evidence on their effectiveness in this capacity is limited. We sought to evaluate the ability of bilevel PAP ST to effect gas exchange via invasive ventilation in a healthy swine model. METHODS: Two single limb respiratory circuits with passive filtered exhalation were constructed and evaluated. Next, two bilevel PAP ST devices, designed for sleep laboratory and home use, were tested on an intubated healthy swine model using these circuits. These devices were compared to an anesthesia ventilator. RESULTS: We evaluated respiratory mechanics, minute ventilation, oxygenation, and presence of rebreathing for all of these devices. Both bilevel PAP ST devices were able to control the measured parameters. There were noted differences in performance between the two devices. Despite these differences, both devices provided effective invasive ventilation by controlling minute ventilation and providing adequate oxygenation in the animal model. CONCLUSIONS: Commercially available bilevel PAP ST can provide invasive ventilation with a single limb respiratory circuit and in-line filters to control oxygenation and ventilation without significant rebreathing in a swine model. Further study is needed to evaluate safety and efficacy in clinical disease models. In the setting of a ventilator shortage during the COVID-19 pandemic, and in other resource-constrained situations, these devices may be considered as an effective alternative means for invasive ventilation.