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Between 1983 and 2012, six giant panda cubs ( Ailuropoda melanoleuca ) born at a zoological institution were stillborn or died between the ages of 3 and 200 h. Two of the six cubs had panhepatic centrilobular hepatic necrosis (CHN), granulocytic extramedullary hematopoiesis (GEM), positive liver culture for Staphylococcus species, and terminal liver failure. Another low-weight cub was administered oxygen therapy immediately after birth and developed hyaline membranes in air spaces and hepatic necrosis restricted to the hilar region. A retrospective analysis of liver and lung lesions, pulmonary microanatomy, blood-gas barrier ultrastructure, and hepatic myofibroblast proliferation was conducted on the six cubs. Neonates with CHN had concurrent severe periportal GEM accompanied by severe myofibroblast proliferation. The pulmonary blood-gas barrier was markedly increased in one cub with CHN. Developmentally, the lungs of all but one cub were at the late saccular stage, and the lowest-weight cub was in early saccular stage, consistent with immaturity, and had pneumonia comparable to neonatal respiratory distress syndrome (RDS). Stage of lung development was eliminated as the primary factor leading to CHN. The pathogenesis of CHN in these neonates is proposed to be transformation of hepatic stellate cells to myofibroblasts initiating blockage and microvascular constriction of hepatic sinusoids, resulting in insufficient perfusion and cellular hypoxia of hepatocytes surrounding central veins in acinar zone 3.

Heterotopic ossification (HO) is a debilitating sequela of high-energy injuries. It frequently requires surgical excision once symptomatic and there is no practical prophylaxis for combat-injured patients. In this study, we examined the effect of local vancomycin powder on HO formation in a small animal model of blast-related, post-traumatic HO. Male Sprague-Dawley rats were subjected to a polytraumatic extremity injury and amputation with or without methicillin-resistant Staphylococcus aureus infection. Animals were randomized to receive a single local application of vancomycin (20 mg/kg) at the time of injury (POD-0, n = 34) or on postoperative day-3 (POD-3, n = 11). Quantitative volumetric measurement of ectopic bone was calculated at 12-weeks post-injury by micro-CT. Bone marrow and muscle tissues were also collected to determine the bacterial burden. Blood for serum cytokine analysis was collected at baseline and post-injury. Vancomycin treatment on POD-0 suppressed HO formation by 86% and prevented bone marrow and soft tissue infections. We concurrently observed a marked reduction histologically in nonviable tissue, chronic inflammatory cell infiltrates, bone infection, fibrous tissue, and areas of bone necrosis within this same cohort. Delayed treatment was significantly less efficacious. Neither treatment had a marked effect on the production of pro-inflammatory cytokines. Our study demonstrates that local vancomycin treatment at the time of injury significantly reduces HO formation in both the presence and absence of infection, with decreased efficacy if not given early. These findings further support the concept that the therapeutic window for prophylaxis is narrow, highlighting the need to develop early treatment strategies for clinical management. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2397-2406, 2017., (© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Background: Tranexamic acid (TXA) is an antifibrinolytic drug that was shown to increase survival in trauma patients, but the mechanisms remain unclear. The purpose of this double-blinded, randomized placebo-controlled study was to determine if TXA with hypotensive resuscitation with Hextend (HEX) or fresh frozen plasma (FFP) reduced blood loss (BL) and improved survival in a model of uncontrolled hemorrhage., Methods: Instrumented, anesthetized pigs (n = 11 per group) were subjected to 24-mL/kg controlled hemorrhage, followed by transection of the spleen. After 15 minutes of bleeding, TXA (1.43 mg/kg/min) or normal saline (NS) was given over 10 minutes, and then 15-mL/kg HEX or FFP was administered. At 90 minutes, a second infusion of TXA or NS was given. BL, coagulation status, and 5-hour survival were determined. Tissue plasminogen activator (tPA) was added to blood samples collected before and after TXA administration to confirm that the TXA inhibited fibrinolysis. In addition, a comparison of a dose response to tPA-induced fibrinolysis was made between swine and human plasma in vitro., Results: TXA prevented the rise in d-dimers that occurred after spleen injury. However, there was no significant effect of TXA on survival or BL compared with NS with HEX (HEX + NS, 17 ± 2 mL/kg vs. HEX + TXA, 17 ± 2 mL/kg) or FFP (FFP + NS, 7 ± 2 mL/kg vs. FFP + TXA, 12 ± 3 mL/kg), while FFP significantly reduced BL and increased survival compared with HEX in the NS-treated animals. The tPA-induced fibrinolysis was inhibited in the blood from TXA-treated animals, yet in fibrinolysis sensitivity studies, human plasma was 30 times more sensitive to tPA-induced fibrinolysis than swine plasma., Conclusion: TXA did not reduce BL, even though TXA was antifibrinolytic in the pigs. The possibility remains that the pig is highly resistant to fibrinolysis and not a good model to study the effects of antifibrinolytics or that fibrinolysis is not a major factor in bleeding from splenic injury.

A near-full-term alpaca (Vicugna pacos) was stillborn 2 days before the expected date of delivery; necropsy examination was conducted within 6 hr of delivery. Gross lesions were enlarged liver and hydrocephalus. On histologic examination, mild inflammatory lesions were identified in the placenta, liver, and lungs, although no etiology was recognized. Within the brain, there was a mild nonsuppurative meningoencephalitis, hydrocephalus, and hydromyelia. Both kidneys had inflammatory foci in cortex and medulla associated with protozoal tissue cysts. Protozoa in brain and kidneys were identified as Toxoplasma gondii based on immunoreactivity to T. gondii polyclonal antibodies that stain both tachyzoites and tissue cysts and BAG1 T. gondii antibodies that are bradyzoite specific. The tissue cysts exhibited intense positivity to T. gondii and mild immunoreactivity to Neospora caninum antibodies. The dam had a high antibody titer (1 : 12,800) to T. gondii and low titer (1 : 100) to N. caninum using their respective agglutination tests. This is the first report of toxoplasmosis-associated abortion in alpaca.

Objective: The role of airway pressure release ventilation in the management of early smoke inhalation injury has not been studied. We compared the effects of airway pressure release ventilation and conventional mechanical ventilation on oxygenation in a porcine model of acute respiratory distress syndrome induced by wood smoke inhalation., Design: Prospective animal study., Setting: Government laboratory animal intensive care unit., Patients: Thirty-three Yorkshire pigs., Interventions: Smoke inhalation injury., Measurements and Main Results: Anesthetized female Yorkshire pigs (n = 33) inhaled room-temperature pine-bark smoke. Before injury, the pigs were randomized to receive conventional mechanical ventilation (n = 15) or airway pressure release ventilation (n = 12) for 48 hrs after smoke inhalation. As acute respiratory distress syndrome developed (PaO2/Fio2 ratio <200), plateau pressures were limited to <35 cm H2O. Six uninjured pigs received conventional mechanical ventilation for 48 hrs and served as time controls. Changes in PaO2/Fio2 ratio, tidal volume, respiratory rate, mean airway pressure, plateau pressure, and hemodynamic variables were recorded. Survival was assessed using Kaplan-Meier analysis. PaO2/Fio2 ratio was lower in airway pressure release ventilation vs. conventional mechanical ventilation pigs at 12, 18, and 24 hrs (p < .05) but not at 48 hrs. Tidal volumes were lower in conventional mechanical ventilation animals between 30 and 48 hrs post injury (p < .05). Respiratory rates were lower in airway pressure release ventilation at 24, 42, and 48 hrs (p < .05). Mean airway pressures were higher in airway pressure release ventilation animals between 6 and 48 hrs (p < .05). There was no difference in plateau pressures, hemodynamic variables, or survival between conventional mechanical ventilation and airway pressure release ventilation pigs., Conclusions: In this model of acute respiratory distress syndrome caused by severe smoke inhalation in swine, airway pressure release ventilation-treated animals developed acute respiratory distress syndrome faster than conventional mechanical ventilation-treated animals, showing a lower PaO2/Fio2 ratio at 12, 18, and 24 hrs after injury. At other time points, PaO2/Fio2 ratio was not different between conventional mechanical ventilation and airway pressure release ventilation.