Does the pediatric hemodynamic cliff exist in response to hemorrhagic shock?

BACKGROUND: The paradigm that children maintain normal blood pressure during hemorrhagic shock until 30%-45% hemorrhage is widely accepted. There are minimal data supporting when decompensation occurs and how a child's vasculature compensates up to that point. We aimed to observe the arterial response to hemorrhage and when mean arterial pressure (MAP) decreased from baseline in pediatric swine. METHODS: Piglets were hemorrhaged in 20% increments of their total blood volume to 60%. MAP and angiograms of the thoracic aorta (TA) and abdominal arteries were obtained. Percent change in area of the vessels from baseline was calculated. RESULTS: Piglets (n = 8) had a differential vasoconstriction starting at 20% hemorrhage (celiac artery 36.3% [31.4-44.6] vs TA 16.7% [10.7-19.1] p = 0.0012). At 40% hemorrhage, the differential vasoconstriction favored shunting blood away from the abdominal visceral branches to the TA (celiac artery 54.7% [36.9-60.6] vs TA 29.5% [23.9-36.2] p = 0.0056 superior mesenteric artery 46.7% [43.9-68.6] vs TA 29.5% [23.9-36.2] p = 0.0100). This was exacerbated at 60% hemorrhage. MAP decreased from baseline at 20% hemorrhage (66.4 ±â€¯6.0 mmHg vs 41.4 ±â€¯10.4 mmHg, p < 0.0001), and worsened at 40% and 60% hemorrhage. CONCLUSION: In piglets, a differential vasocontriction shunting blood proximally occurred in response to hemorrhage. This did not maintain normal MAP at 20%, 40% or 60% hemorrhage. LEVEL OF EVIDENCE: Level II.

Reperfusion repercussions: A review of the metabolic derangements following resuscitative endovascular balloon occlusion of the aorta.

BACKGROUND: Current resuscitative endovascular balloon occlusion of the aorta (REBOA) literature focuses on improving outcomes through careful patient selection, diligent catheter placement, and expeditious definitive hemorrhage control. However, the detection and treatment of post-REBOA ischemia-reperfusion injury (IRI) remains an area for potential improvement. Herein, we provide a review of the metabolic derangements that we have encountered while managing post-REBOA IRI in past swine experiments. We also provide data-driven clinical recommendations to facilitate resuscitation post-REBOA deflation that may be translatable to humans. METHODS: We retrospectively reviewed the laboratory data from 25 swine across three varying hemorrhagic shock models that were subjected to complete REBOA of either 45 minutes, 60 minutes, or 90 minutes. In each model the balloon was deflated gradually following definitive hemorrhage control. Animals were then subjected to whole blood transfusion and critical care with frequent electrolyte monitoring and treatment of derangements as necessary. RESULTS: Plasma lactate peaked and pH nadired long after balloon deflation in all swine in the 45-minute, 60-minute, and 90-minute occlusion models (onset of peak lactate, 32.9 ± 6.35 minutes, 38.8 ± 10.55 minutes, and 49.5 ± 6.5 minutes; pH nadir, 4.3 ± 0.72 minutes, 26.9 ± 12.32 minutes, and 42 ± 7.45 minutes after balloon deflation in the 45-, 60-, and 90-minute occlusion models, respectively). All models displayed persistent hypoglycemia for more than an hour following reperfusion (92.1 ± 105.5 minutes, 125 ± 114.9 minutes, and 96 ± 97.8 minutes after balloon deflation in the 45-, 60-, and 90-minute occlusion groups, respectively). Hypocalcemia and hyperkalemia occurred in all three groups, with some animals requiring treatment more than an hour after reperfusion. CONCLUSION: Metabolic derangements resulting from REBOA use are common and may worsen long after reperfusion despite resuscitation. Vigilance is required to detect and proactively manage REBOA-associated IRI. Maintaining a readily available "deflation kit" of pharmacological agents needed to treat common post-REBOA electrolyte abnormalities may facilitate management. LEVEL OF EVIDENCE: Level V.

Resuscitative endovascular balloon occlusion of the aorta in a pediatric swine model: Is 60 minutes too long?

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is recommended in adults with a noncompressible torso hemorrhage with occlusion times of less than 60 minutes. The tolerable duration in children is unknown. We used a pediatric swine controlled hemorrhage model to evaluate the physiologic effects of 30 minutes and 60 minutes of REBOA. METHODS: Pediatric swine weighing 20 kg to 30 kg underwent a splenectomy and a controlled 60% total blood volume hemorrhage over 30 minutes, followed by either zone 1 REBOA for 30 minutes (30R) or 60 minutes (60R). Swine were then resuscitated with shed blood and received critical care for 240 minutes. RESULTS: During critical care, the 30R group's (n = 3) pH, bicarbonate, base excess, and lactate were no different than baseline, while at the end of critical care, these variables continued to differ from baseline in the 60R group (n = 5) and were worsening (7.4 vs. 7.2, p < 0.001, 30.4 mmol/L vs. 18.4 mmol/L, p < 0.0001, 5.6 mmol/L vs. -8.5 mmol/L, p < 0.0001, 2.4 mmol/L vs. 5.7 mmol/L, p < 0.001, respectively). Compared with baseline, end creatinine and creatinine kinase were elevated in 60R swine (1.0 mg/dL vs. 1.7 mg/dL, p < 0.01 and 335.4 U/L vs. 961.0 U/L, p < 0.001, respectively), but not 30R swine (0.9 mg/dL vs. 1.2 mg/dL, p = 0.06 and 423.7 U/L vs. 769.5 U/L, p = 0.15, respectively). There was no difference in survival time between the 30R and 60R pediatric swine, p = 0.99. CONCLUSION: The physiologic effects of 30 minutes of zone 1 REBOA in pediatric swine mostly resolved during the subsequent 4 hours of critical care, whereas the effects of 60 minutes of REBOA persisted and worsened after 4 hours of critical care. Sixty minutes of zone 1 REBOA may create an irreversible physiologic insult in a pediatric population.

Not ready for prime time: Intermittent versus partial resuscitative endovascular balloon occlusion of the aorta for prolonged hemorrhage control in a highly lethal porcine injury model.

BACKGROUND: Partial resuscitative endovascular balloon occlusion of the aorta (pREBOA) and intermittent REBOA (iREBOA) are techniques to extend the therapeutic duration of REBOA by balloon titration for distal flow or cyclical balloon inflation/deflation to allow transient distal flow, respectively. We hypothesized that manually titrated pREBOA would reduce blood losses and ischemic burden when compared with iREBOA. METHODS: Following 20% blood volume controlled hemorrhage, 10 anesthetized pigs underwent uncontrolled hemorrhage from the right iliac artery and vein. Once in hemorrhagic shock, animals underwent 15 minutes of complete zone 1 REBOA followed by 75 minutes of either pREBOA or iREBOA (n = 5/group). After 90 minutes, definitive hemorrhage control was obtained, animals were resuscitated with the remaining collected blood, and then received 2 hours of critical care. RESULTS: There were no differences in mortality. Animals randomized to iREBOA spent a larger portion of the time at full occlusion when compared with pREBOA (median, 70 minutes; interquartile range [IQR], 70-80 vs. median, 20 minutes; IQR, 20-40, respectively; p = 0.008). While the average blood pressure during the intervention period was equivalent between groups, this was offset by large fluctuations in blood pressure and significantly more rescue occlusions for hypotension with iREBOA. Despite lower maximum aortic flow rates, the pREBOA group tolerated a greater total amount of distal aortic flow during the intervention period (median, 20.9 L; IQR, 20.1-23.0 vs. median, 9.8 L; IQR, 6.8-10.3; p = 0.03) with equivalent abdominal blood losses. Final plasma lactate and creatinine concentrations were equivalent, although iREBOA animals had increased duodenal edema on histology. CONCLUSION: Compared with iREBOA, pREBOA reduced the time spent at full occlusion and the number of precipitous drops in proximal mean arterial pressure while delivering more distal aortic flow but not increasing total blood loss in this highly lethal injury model. Neither technique demonstrated a survival benefit. Further refinement of these techniques is necessary before clinical guidelines are issued.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) in a pediatric swine liver injury model: A pilot study.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) has not been studied in children. We hypothesized that REBOA was feasible and would improve hemorrhage control and survival time, compared to no aortic occlusion, in a pediatric swine liver injury model. METHODS: Pediatric swine were randomized to Zone 1 REBOA or no intervention (control). Piglets underwent a partial liver amputation and free hemorrhage followed by either REBOA or no intervention for 30 min, then a damage control laparotomy and critical care for 4 h. RESULTS: Compared to control piglets (n = 5), REBOA piglets (n = 6) had less blood loss (34.0 ±â€¯1.6 vs 61.3 ±â€¯2.5 mL/kg, p < 0.01), higher end hematocrit (28.1 ±â€¯2.1 vs 17.1 ±â€¯4.1%, p = 0.03), higher end creatinine (1.4 ±â€¯0.1 vs 1.2 ±â€¯0.1 mg/dL, p = 0.05), higher end ALT and AST (56 ±â€¯4 vs 32 ±â€¯6 U/L, p = 0.01 and 155 ±â€¯26 vs 69 ±â€¯25 U/L, p = 0.05) and required more norepinephrine during critical care (1.4 ±â€¯0.3 vs 0.3 ±â€¯0.3 mg/kg, p = 0.04). All REBOA piglets survived, whereas 2 control piglets died, p = 0.10. CONCLUSION: In pediatric swine, 30 min of REBOA is feasible, decreases blood loss after liver injury and may improve survival. LEVEL OF EVIDENCE: Level 1.

Extracorporeal potassium binding for the management of hyperkalemia in an anephric model of crush injury.

BACKGROUND: Potassium-binding polymers have shown promising results in an anephric porcine hyperkalemia model. The benefits of the polymer in a clinically relevant injury model remain unknown. We hypothesized that potassium-binding cartridges would control serum potassium concentration in a porcine hemorrhagic shock model with supraceliac aortic occlusion and a limb crush injury. METHODS: Ten Yorkshire-cross swine were anesthetized and instrumented. Pigs underwent splenectomy and bilateral nephrectomy. Hemorrhagic shock was induced for 30 minutes while a leg compression device was applied. Pigs underwent supraceliac aortic occlusion for 60 minutes and were resuscitated with shed blood. The leg compression device was removed 20 minutes after balloon deflation. After 20 minutes of reperfusion, animals were randomized to extracorporeal circulation with (treatment) or without (control) the potassium binding cartridges. In both groups, blood was circulated through a hemodialyzer with a peristaltic pump. In the treatment group, the ultrafiltrate was diverted from the hemodialyzer through cartridges containing the polymer and returned to the extracorporeal circuit. Animals were resuscitated with 0.9% saline boluses and a norepinephrine infusion. The change in serum potassium concentration (ΔK) was calculated as serum [K]T390 - serum [K]T0. RESULTS: There was a significant difference in serum potassium concentration between groups (p < 0.001). ΔK was significantly higher in the control than the treatment group (3.75 [3.27-4.42] and 1.15 [0.62-1.59] mmol/L, respectively; p = 0.03). There were no differences in mean arterial pressure (p = 0.14), isotonic crystalloids requirement (p = 0.51), or norepinephrine dose (p = 0.83) between groups. Serum lactate concentration was significantly higher in the control group (p < 0.001). At the end of the experiment, the [K] was reduced by 25% (24.9%-27.8%) across the cartridges. CONCLUSION: The cartridges controlled serum potassium concentrations without dialysate and retained potassium binding capabilities over 4 hours. There were no deleterious effects on hemodynamic parameters. Those cartridges might be beneficial adjuncts for hyperkalemia management in austere environments. LEVEL OF EVIDENCE: Translational science study, level I.

Endocrine Effects of Simulated Complete and Partial Aortic Occlusion in a Swine Model of Hemorrhagic Shock.

INTRODUCTION: Low distal aortic flow via partial aortic occlusion (AO) may mitigate ischemia induced by resuscitative endovascular balloon occlusion of the aorta (REBOA). We compared endocrine effects of a novel simulated partial AO strategy, endovascular variable aortic control (EVAC), with simulated REBOA in a swine model. MATERIALS AND METHODS: Aortic flow in 20 swine was routed from the supraceliac aorta through an automated extracorporeal circuit. Following liver injury-induced hemorrhagic shock, animals were randomized to control (unregulated distal flow), simulated REBOA (no flow, complete AO), or simulated EVAC (distal flow of 100-300 mL/min after 20 minutes of complete AO). After 90 minutes, damage control surgery, resuscitation, and full flow restoration ensued. Critical care was continued for 4.5 hours or until death. RESULTS: Serum angiotensin II concentration was higher in the simulated EVAC (4,769 ± 624 pg/mL) than the simulated REBOA group (2649 ± 429) (p = 0.01) at 180 minutes. There was no detectable difference in serum renin [simulated REBOA: 231.3 (227.9-261.4) pg/mL; simulated EVAC: 294.1 (231.2-390.7) pg/mL; p = 0.27], aldosterone [simulated EVAC: 629 (454-1098), simulated REBOA: 777 (575-1079) pg/mL, p = 0.53], or cortisol (simulated EVAC: 141 ± 12, simulated REBOA: 127 ± 9 ng/mL, p = 0.34) concentrations between groups. CONCLUSIONS: Simulated EVAC was associated with higher serum angiotensin II, which may have contributed to previously reported cardiovascular benefits. Future studies should evaluate the renal effects of EVAC and the concomitant therapeutic use of angiotensin II.

Endovascular variable aortic control (EVAC) versus resuscitative endovascular balloon occlusion of the aorta (REBOA) in a swine model of hemorrhage and ischemia reperfusion injury.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is effective at limiting hemorrhage from noncompressible sources and restoring but causes progressive distal ischemia, supraphysiologic pressures, and increased cardiac afterload. Endovascular variable aortic control (EVAC) addresses these limitations, while still controlling hemorrhage. Previous work demonstrated improved outcomes following a 90-minute intervention period in an uncontrolled hemorrhage model. The present study compares automated EVAC to REBOA over an occlusion period reflective of contemporary REBOA usage. METHODS: Following instrumentation, 12 Yorkshire-cross swine underwent controlled 25% hemorrhage, a 45-minute intervention period of EVAC or REBOA, and subsequent resuscitation with whole blood and critical care for the remainder of a 6-hour experiment. Hemodynamics were acquired continuously, and laboratory parameters were assessed at routine intervals. Tissue was collected for histopathologic analysis. RESULTS: No differences were seen in baseline parameters. During intervention, EVAC resulted in more physiologic proximal pressure augmentation compared with REBOA (101 vs. 129 mm Hg; 95% confidence interval [CI], 105-151 mm Hg; p = 0.04). During critical care, EVAC animals required less than half the amount of crystalloid (3,450 mL; 95% CI, 1,215-5,684 mL] vs. 7,400 mL [95% CI, 6,148-8,642 mL]; p < 0.01) and vasopressors (21.5 ng/kg [95% CI, 7.5-35.5 ng/kg] vs. 50.5 ng/kg [95% CI, 40.5-60.5 ng/kg]; p = 0.05) when compared with REBOA animals. Endovascular variable aortic control resulted in lower peak and final lactate levels. Endovascular variable aortic control animals had less aortic hyperemia from reperfusion with aortic flow rates closer to baseline (36 mL/kg per minute [95% CI, 30-44 mL/kg per minute] vs. 51 mL/kg per minute [95% CI, 41-61 mL/kg per minute]; p = 0.01). CONCLUSIONS: For short durations of therapy, EVAC produces superior hemodynamics and less ischemic insult than REBOA in this porcine-controlled hemorrhage model, with improved outcomes during critical care. This study suggests EVAC is a viable strategy for in-hospital management of patients with hemorrhagic shock from noncompressible sources. Survival studies are needed to determine if these early differences persist over time.

Location is everything: The hemodynamic effects of REBOA in Zone 1 versus Zone 3 of the aorta.

OBJECTIVES: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an emerging technology to augment proximal blood pressure during the resuscitation of patients with noncompressible torso hemorrhage. Currently, placement choice, supraceliac (Zone 1) versus infrarenal (Zone 3) aorta, depends on injury patterns, but remains a highly debated topic. We sought to compare the proximal hemodynamic support provided by Zone 1 versus Zone 3 REBOA placement and the degree of hemodynamic instability upon reperfusion following intervention. METHODS: Eighteen anesthetized swine underwent controlled hemorrhage of 25% total blood volume, followed by 45 minutes of Zone 1 REBOA, Zone 3 REBOA, or no intervention (control). They were then resuscitated with shed blood, aortic balloons were deflated, and 5 hours of critical care ensued prior to euthanasia. Physiologic parameters were recorded continuously, and blood was drawn for analysis at specified intervals. Significance was defined as p < 0.05. RESULTS: There were no significant differences between groups at baseline or during the initial 30 minutes of hemorrhage. During the intervention period, average proximal MAP was significantly greater in Zone 1 animals when compared with Zone 3 animals (127.9 ± 1.3 vs. 53.4 ± 1.1 mm Hg) and greater in Zone 3 animals when compared with control animals (42.9 ± 0.9 mm Hg). Lactate concentrations were significantly higher in Zone 1 animals (9.6 ± 0.4 mmol/L) when compared with Zone 3 animals (5.1 ± 0.3 mmol/L) and control animals (4.2 ± 0.8 mmol/L). CONCLUSIONS: In our swine model of hemorrhagic shock, Zone 3 REBOA provided minimal proximal hemodynamic support when compared with Zone 1 REBOA, albeit with less ischemic burden and instability upon reperfusion. In cases of impending hemodynamic collapse, Zone 1 REBOA placement may be more efficacious regardless of injury pattern, whereas Zone 3 should be reserved only for relatively stable patients with ongoing distal hemorrhage.

Lower extremity cooling reduces ischemia-reperfusion injury following Zone 3 REBOA in a porcine hemorrhage model.

BACKGROUND: New strategies to mitigate ischemia during REBOA and to prolong its maximal duration are needed. We hypothesized that simple external cooling of the hind limbs would decrease ischemia-reperfusion injury following prolonged Zone 3 REBOA. METHODS: Twelve swine were anesthetized, instrumented, splenectomized, and then underwent 15% total blood volume hemorrhage. Animals were randomized to hypothermia or control followed by 4 hours of Zone 3 REBOA, resuscitation with shed blood, and 3 hours of critical care. Physiologic parameters were continuously recorded, and laboratory specimens were obtained at regular intervals. Baseline and end-of-study muscle biopsies were obtained for histologic analysis. RESULTS: There were no significant differences between groups at baseline or after hemorrhage. Maximum creatine kinase was significantly lower in the hypothermia group compared with the normothermia group (median [interquartile range] = 3,445 U/mL [3,380-4,402 U/mL] vs. 22,544 U/mL [17,030-24,981 U/mL]; p < 0.01). Maximum serum myoglobin was also significantly lower in the hypothermia group (1,792 ng/mL [1,250-3,668 ng/mL] vs. 21,186 ng/mL [14,181-24,779 ng/mL]; p < 0.01). Fascial compartment pressures were significantly lower during critical care in the hypothermia group (p = 0.03). No histologic differences were observed in hind limb skeletal muscle. CONCLUSIONS: External cooling during prolonged Zone 3 REBOA decreased ischemic muscle injury and resulted in lower compartment pressures following reperfusion. Hypothermia may be a viable option to extend the tolerable duration of Zone 3 occlusion, beyond what is currently achievable. Future survival studies are required to assess functional outcomes.

Extracellular matrix scaffolds for treatment of large volume muscle injuries: A review.

OBJECTIVE: Large muscular or musculotendinous defects present a dilemma because of the inadequacies of current treatment strategies. Extracellular matrices (ECM) are potential clinically applicable regenerative biomaterials. This review summarizes information from the preclinical literature evaluating the use of ECM for muscle regeneration in animal models of volumetric muscle loss (VML). STUDY DESIGN: Literature review. SAMPLE POPULATION: Animal models of VML in which surgical repair was performed with an ECM product, with or without added cell populations. METHODS: PubMed, Google Scholar, CAB abstracts, and Scopus were searched for preclinical studies using ECM in animal models of VML. The search terms "extracellular matrix," "VML," "muscle regeneration," "cell seeded," and "scaffold" identified 40 articles that met inclusion criteria of an animal model of VML in which surgical repair was performed with an ECM product, with or without added cell populations. Key skeletal muscle repair mechanisms and experimental findings on scaffold type, VML location, and experimental animal species were summarized. CONCLUSIONS: Satellite cells and basal lamina are key endogenous contributors to skeletal muscle regeneration. ECM as a dynamic tissue component may provide structural integrity, signaling molecules, and a 3-dimensional topography conducive to muscle regeneration. Preclinical models of muscle repair most commonly used mice and rats (88%). Most experimental lesions were created in abdominal wall (33%), anterior tibialis (33%), latissimus dorsi (10%), or quadriceps (10%) muscles. Matrices varied markedly in source and preparation. Experimental outcomes of ECM and cell-seeded ECM implantation for muscle regeneration in VML were highly variable and dependent on matrix tissue source, preparation method, and anatomic site of injury. Scar tissue formation likely contributes to load transfer. Nonappendicular lesions had better regenerative results compared with appendicular VML. CLINICAL SIGNIFICANCE: The preponderance of current evidence supports the use of ECM for muscle defect repair only in specific instances, such as nonappendicular and/or partial-thickness defects. Consequently, clinical use of ECM in veterinary patients requires careful consideration of the specific ECM product, lesion size and location, and loading circumstances.

Comparison of direct site endovascular repair utilizing expandable polytetrafluoroethylene stent grafts versus standard vascular shunts in a porcine (Sus scrofa) model.

INTRODUCTION: The small diameter of temporary vascular shunts for vascular trauma management may restrict flow and result in ischemia or early thrombosis. We have previously reported a clinical experience with direct, open surgical reconstruction using expandable polytetrafluoroethylene stent grafts to create a "sutureless" anastomosis as an alternative to standard temporary vascular shunts. We sought to characterize patency and flow characteristics of these grafts compared with standard shunts in a survival model of porcine vascular injury. METHODS: Twelve Yorkshire-cross swine received a 2-cm-long near-circumferential defect in the bilateral iliac arteries. A 14 Fr Argyle shunt was inserted into one randomly assigned artery, with a self-expanding expandable polytetrafluoroethylene stent deployed in the other. At 72 hours, conduit patency was evaluated by angiography. Arterial flow measurements were obtained at baseline, immediately after intervention, and after 72 hours via direct measurement with perivascular flow meters. Blood pressure proximal and distal to the conduits and arterial samples for histopathology were obtained during the terminal procedure. RESULTS: Angiography revealed no difference in patency at 72 hours (p = 1.0). While there was no difference in baseline arterial flow between arteries (p = 0.63), the stent grafts demonstrated significantly improved blood flow compared with shunts both immediately after intervention (390 ± 36 mL/min vs. 265 ± 25 mL/min, p = 0.002) and at 72 hours (261 ± 29 mL/min vs. 170 ± 36 mL/min, p = 0.005). The pressure gradient across the shunts was greater than that of the stent grafts (11.5 mm Hg [interquartile range, 3-19 mm Hg] vs. 3 mm Hg [interquartile range, 3-5 mm Hg], p = 0.013). The speed of deployment was similar between the two devices. CONCLUSIONS: Open "sutureless" direct site repair using commercially available stent grafts to treat vascular injury is a technically feasible strategy for damage control management of peripheral vascular injury and offers increased blood flow when compared with temporary shunts. Furthermore, stent grafts may offer improved durability to extend the window until definitive vascular repair. The combination of these traits may improve outcomes after vascular injury. LEVEL OF EVIDENCE: Epidemiologic/Prognostic, level III.

The effect of resuscitative endovascular balloon occlusion of the aorta, partial aortic occlusion and aggressive blood transfusion on traumatic brain injury in a swine multiple injuries model.

BACKGROUND: Despite clinical reports of poor outcomes, the degree to which resuscitative endovascular balloon occlusion of the aorta (REBOA) exacerbates traumatic brain injury (TBI) is not known. We hypothesized that combined effects of increased proximal mean arterial pressure (pMAP), carotid blood flow (Qcarotid), and intracranial pressure (ICP) from REBOA would lead to TBI progression compared with partial aortic occlusion (PAO) or no intervention. METHODS: Twenty-one swine underwent a standardized TBI via computer Controlled cortical impact followed by 25% total blood volume rapid hemorrhage. After 30 minutes of hypotension, animals were randomized to 60 minutes of continued hypotension (Control), REBOA, or PAO. REBOA and PAO animals were then weaned from occlusion. All animals were resuscitated with shed blood via a rapid blood infuser. Physiologic parameters were recorded continuously and brain computed tomography obtained at specified intervals. RESULTS: There were no differences in baseline physiology or during the initial 30 minutes of hypotension. During the 60-minute intervention period, REBOA resulted in higher maximal pMAP (REBOA, 105.3 ± 8.8; PAO, 92.7 ± 9.2; Control, 48.9 ± 7.7; p = 0.02) and higher Qcarotid (REBOA, 673.1 ± 57.9; PAO, 464.2 ± 53.0; Control, 170.3 ± 29.4; p < 0.01). Increases in ICP were greatest during blood resuscitation, with Control animals demonstrating the largest peak ICP (Control, 12.8 ± 1.2; REBOA, 5.1 ± 0.6; PAO, 9.4 ± 1.1; p < 0.01). There were no differences in the percentage of animals with hemorrhage progression on CT (Control, 14.3%; 95% confidence interval [CI], 3.6-57.9; REBOA, 28.6%; 95% CI, 3.7-71.0; and PAO, 28.6%; 95% CI, 3.7-71.0). CONCLUSION: In an animal model of TBI and shock, REBOA increased Qcarotid and pMAP, but did not exacerbate TBI progression. PAO resulted in physiology closer to baseline with smaller increases in ICP and pMAP. Rapid blood resuscitation, not REBOA, resulted in the largest increase in ICP after intervention, which occurred in Control animals. Continued studies of the cerebral hemodynamics of aortic occlusion and blood transfusion are required to determine optimal resuscitation strategies for multi-injured patients.

A pilot study of chest tube versus pigtail catheter drainage of acute hemothorax in swine.

BACKGROUND: Evacuation of traumatic hemothorax (HTx) is typically accomplished with large-bore (28-40 Fr) chest tubes, often resulting in patient discomfort. Management of HTx with smaller (14 Fr) pigtail catheters has not been widely adopted because of concerns about tube occlusion and blood evacuation rates. We compared pigtail catheters with chest tubes for the drainage of acute HTx in a swine model. METHODS: Six Yorkshire cross-bred swine (44-54 kg) were anesthetized, instrumented, and mechanically ventilated. A 32 Fr chest tube was placed in one randomly assigned hemithorax; a 14 Fr pigtail catheter was placed in the other. Each was connected to a chest drainage system at -20 cm H2O suction and clamped. Over 15 minutes, 1,500 mL of arterial blood was withdrawn via femoral artery catheters. Seven hundred fifty milliliters of the withdrawn blood was instilled into each pleural space, and fluid resuscitation with colloid was initiated. The chest drains were then unclamped. Output from each drain was measured every minute for 5 minutes and then every 5 minutes for 40 minutes. The swine were euthanized, and thoracotomies were performed to quantify the volume of blood remaining in each pleural space and to examine the position of each tube. RESULTS: Blood drainage was more rapid from the chest tube during the first 3 minutes compared with the pigtail catheter (348 ± 109 mL/min vs. 176 ± 53 mL/min), but this difference was not statistically significant (p = 0.19). Thereafter, the rates of drainage between the two tubes were not substantially different. The chest tube drained a higher total percentage of the blood from the chest (87.3% vs. 70.3%), but this difference did not reach statistical significance (p = 0.21). CONCLUSION: We found no statistically significant difference in the volume of blood drained by a 14 Fr pigtail catheter compared with a 32 Fr chest tube.

Effect of fish oil supplementation in a rat model of multiple mild traumatic brain injuries.

PURPOSE: Repetitive mild traumatic brain injury (TBI) is a major military and sports health concern. The purpose of this study was to determine if a diet rich in omega-3 fatty acids would reduce cognitive deficits and neuronal cell death in a novel fluid percussion rat model of repetitive mild TBIs. METHODS: Thirty-two Sprague-Dawley rats were assigned to either an experimental rat chow enhanced with 6% fish oil (source of omega-3 fatty acids) or a control rat chow. Both rat chows contained equivalent quantities of calories, oil, and nutrients. After four weeks, both groups received mild repetitive bilateral fluid percussion TBIs on two sequential days. Pre-injury diets were resumed, and the animals were monitored for two weeks. On post-injury days 10-14, Morris Water Maze testing was performed to assess spatial learning and cognitive function. Animals were euthanized at 14 days post-injury to obtain specimens for neurohistopathology. RESULTS: There was no difference in pre-injury weight gain between groups. Post-injury, animals on the fish oil diet lost less weight and recovered their weight significantly faster. By 14 days, the fish oil diet group performed significantly better in the Morris Water Maze. Neurohistopathology identified a non-significant trend toward a higher density of hippocampal neurons in the fish oil diet group. CONCLUSIONS: Pre-injury dietary supplementation with fish oil improves recovery of body weight and provides a small improvement in cognitive performance in a rat model of multiple mild TBIs.

Pharmacokinetics of oxymorphone in titi monkeys (Callicebus spp.) and rhesus macaques (Macaca mulatta).

Oxymorphone is a pure µ-opioid receptor agonist that is commonly used in nonhuman primate medicine and surgery to minimize pain ranging in intensity from moderate to severe. We compared pharmacokinetic profiles and physiologic and behavioral responses to oxymorphone between titi monkeys (Callicebus spp.) and rhesus macaques (Macaca mulatta). Titi monkeys (n = 4) and rhesus macaques (n = 4) were injected intravenously with either a bolus of 0.075 mg/kg oxymorphone or placebo on multiple occasions, with a minimal washout period of 14 d between trials. Blood collection was limited to no more than 3 samples per trial, with samples collected at multiple time points until 10 h after injection. Collection periods, animal order, and testing day were randomized. In addition, macaques underwent a single serial collection at all time points to validate study design. A 2-compartment model best described the disposition of oxymorphone in both species. Clearance was faster in macaques than titi monkeys, in which terminal half-life was longer. Statistically significant physiologic differences were found between species and between treatments within species. Apart from these effects, oxymorphone did not significantly change physiologic parameters over time. After oxymorphone treatment, macaques demonstrated behaviors reflecting pruritis, whereas titi monkeys exhibited sedation. Despite its mild side effects, we recommend the consideration of oxymorphone for pain management protocols in both Old and New World nonhuman primates.

In utero repair of gastroschisis in the sheep (Ovis aries) model.

OBJECTIVE: Gastroschisis is associated with inflammatory changes in the exposed bowel which leads to intestinal dysmotility after postnatal repair. The insult is a combined effect of amniotic fluid exposure and mechanical constriction. We hypothesized that in utero anatomic repair is possible in a sheep model, and that it may halt the inflammatory damage caused by both mechanisms. METHODS: Gastroschisis was surgically created in mid-gestation (day 75) in 8 sheep fetuses. On gestational day 100, 2 fetuses underwent open fetal gastroschisis repair, where the eviscerated bowel was returned to the peritoneal cavity, and the abdominal wall was primarily closed. All fetuses were harvested at 135 days of gestation. RESULTS: Six fetuses survived the initial operation, and both fetuses that underwent gastroschisis repair survived to term. At 100 and 135 days of gestation, the eviscerated bowel showed progressive signs of inflammation and peel development. The gross and microscopic inflammatory changes in the gastroschisis bowel at 100 days of gestation were completely resolved at term following in utero repair. CONCLUSION: In utero anatomic repair of gastroschisis is possible in mid-gestation in the fetal lamb model, and it appears to ameliorate the inflammatory process.

Preliminary study of the effects of smectite granules (WoundStat) on vascular repair and wound healing in a swine survival model.

BACKGROUND: WoundStat (WS) (TraumaCure, Bethesda, MD) is a topical hemostatic agent that effectively stops severe hemorrhage in animal models. To the best of our knowledge, no survival study has been conducted to ensure long-term product safety. We evaluated vascular patency and tissue responses to WS in a swine femoral artery injury model with survival up to 5 weeks. METHODS: Anesthetized swine received a standardized femoral artery injury with free hemorrhage for 45 seconds followed by WS application. One hour after application, the WS was removed, the wound copiously irrigated, and the artery repaired using a vein patch. Six groups of three animals received WS and were killed either immediately after surgery or at weekly intervals up to 5 weeks. Three control animals were treated with gauze packing and direct pressure followed by identical vascular repair and survival for 1 week. At the time of killing, angiograms were performed, and tissue was collected for histopathology. RESULTS: Hemostasis was complete in all WS animals. All animals survived the procedure, and there were no clinically evident postoperative complications. Vascular repairs were angiographically patent in 15 of 18 animals (83%) receiving WS. Histopathologic examination of WS animals revealed severe diffuse fibrogranulomatous inflammation, early endothelial degeneration with subsequent intimal hyperplasia, moderate myocyte necrosis, and fibrogranulomatous nerve entrapment with axonal degeneration. CONCLUSION: Although an effective hemostatic agent, WS use was associated with a substantial local inflammatory response and neurovascular changes up to 5 weeks postinjury.

Radio frequency radiation exposure of the F-15 crewmember.

INTRODUCTION: In the United States Air Force, pilots of F-15 fighter aircraft use fire control radars to search for enemy targets and to launch beyond visual range radar missiles. The fire control radars must be of a sufficient power output to enable a target return, but pilots are concerned about deleterious health effects from the levels of radio frequency radiation (RFR) they are exposed to. Measurement of RFR while actually in flight in the F-15 has never been performed. This study was designed to document the RFR levels that pilots are exposed to on normal missions while in flight with the radar on and active. METHODS: A hand-held meter was used to measure electromagnetic fields during three F-15 flights. Instrumentation consisted of a Narda Microwave Model 8718 digital survey meter and Model 8723 broadband isotropic E-field probe with a frequency range between 300 MHz and 50 GHz. The measurements were conducted in the rear cockpit of an F-15D aircraft. Three missions were flown representing the standard missions an F-15 pilot flies on an everyday basis. The missions were: night intercepts, offensive basic fighter maneuvers, and defensive basic fighter maneuvers. RESULT: Based on the data collected during three F-15 missions, all recorded RFR exposure to the crewmember in the F-15 was within the OSHA Permissible Exposure Limit (PEL) of 10 mW x cm(-2). CONCLUSION: Based on a limited sample, RFR exposures in F-15 cockpits appear to be well below the PEL.

Introduction; The history of public health and veterinary public service; Historic and future perspectives of the American College of Veterinary Preventive Medicine; Blue ribbon task force report on the future of Food Safety and Inspection Service veterinarians: public health professionals for the 21st century; The National Antimicrobial Resistance Monitoring System (NARMS) for enteric bacteria,1996- 1999: surveillance for action; Public health education of veterinarians and veterinary students for the future; Ten great veterinary public health/preventive medicine achievements in the United States, 1901 to 2000.

Historically, veterinary medicine has made its greatest contributions in the public sector and in settings other than direct care of the individual patient. So why are so many of us unaware of our profession's achievements in this arena? My introduction to veterinary preventive medicine and public health was through military service. My obligation to serve a two-year doctor draft in the United States Air Force became an adventure for my family and me, rather than an unwelcome intrusion on my ultimate desire to return to private clinical practice. The operative words are private and clinical. Why was I unaware of the opportunities available to those of us educated in this discipline sometimes referred to as comparative medicine?