Intense Light Pretreatment Improves Hemodynamics, Barrier Function and Inflammation in a Murine Model of Hemorrhagic Shock Lung

Introduction Hemorrhagic shock is a primary injury amongst combat casualties. Hemorrhagic shock can lead to acute lung injury, which has a high mortality rate. Based on studies showing the role of intense light for organ-protection, we sought to evaluate if intense light pretreatment would be protective in a murine model of hemorrhagic shock lung. Materials and Methods After exposure to standard room light or to intense light (10 000 LUX), mice were hemorrhaged for 90 minutes to maintain a mean arterial pressure (MAP) of 30–35 mmHg. Mice were then resuscitated with their blood and a NaCl infusion at a rate of 0.2 ml/h over a 3-hour period. During resuscitation, blood pressure was recorded. At the end of resuscitation, bronchoalveolar lavage was analyzed for alveolar epithelial barrier function and inflammation. To get insight into the relevance of intense light for humans, we performed a proteomics screen for lung injury biomarkers in plasma from healthy volunteers following intense light therapy. Results We found that intense light pretreated mice had improved hemodynamics and significantly lower albumin, IL-6, and IL-8 levels in their bronchoalveolar lavage than controls. We further discovered that intense light therapy in humans significantly downregulated proinflammatory plasma proteins that are known to cause acute lung injury. Conclusions Our data demonstrate that mice exposed to intense light before hemorrhagic shock lung have less lung inflammation and improved alveolar epithelial barrier function. We further show that intense light therapy downregulates lung injury promoting proteins in human plasma. Together, these data suggest intense light as a possible strategy to ameliorate the consequences of a hemorrhagic shock on lung injury.

Efficacy of Body Armor in Protection against Blast Injuries using a Swine Model in a Confined Space with a Blast Tube

Background Regarding blast injuries, fatal damage leading to immediate death is considered due to shock-lung, respiratory arrest, or circulatory failure induced by a neurological reflex, such as the severe vagal nerve reflex. It has not yet been determined whether a bulletproof vest protects against or aggravates shock-lung or the neurological reflexes considered to be fatal in the super-acute phase after an explosion. Purpose The purpose of this study was to clarify whether a bulletproof vest would protect the body in a pig blast model using a blast tube built at National Defense Medical College, which is the first such blast tube in Japan. Methods Seventeen pigs were divided into two groups: the body armor group (n = 6) and the non-body armor group (n = 11). Pigs underwent tracheal intubation with IV and A lines were secured to measure vital signs were checked and collect blood samples. Then, under intravenous anesthesia, the pigs were tightly fixed in the left lateral position on a table and exposed from the back neck to the upper lumbar back to the blast wave and wind with or without body armor, with the driving pressure of the blast tube set to 3.0 MPa. We checked the vital signs, collected blood samples, and observed the pigs for 3 hours after injury. Results When the surviving and dead pigs were compared, blood gas analyses revealed significant differences in PaO2, PaCO2, and pH in the super-early phase. In addition, all pigs injured by the blast wave and wind had lung hemorrhage, and 14 of 17 pigs had intra-abdominal hemorrhage with splenic injury. All 6 animals in the body armor group and 6 of the 11 animals in the control group survived for 3 hours after injury. Respiratory arrest immediately after exposure to the blast wave and wind was considered to influence the outcome in our pig model. Conclusions Respiratory arrest within several minutes after injury influenced the mortality of pigs. Body armor may have the beneficial effect in protecting against respiratory arrest immediately after an explosion.

The Role of Recipient Platelets In the Prevention of Antibody-Mediated Transfusion Related Acute Lung Injury (TRALI)

Abstract 3351 Transfusion related acute lung injury (TRALI) is a serious complication of transfusion. The pathogenesis of TRALI is not fully understood but previous findings have suggested that platelet depletion can protect mice in a two-hit model of TRALI (Looney et al J Clin Invest 119:3450, 2009). To further understand the role of platelets in preventing antibody-mediated TRALI, two mouse models of immune thrombocytopenia (ITP) were utilized. In the passive ITP model, SCID mice were injected with a monoclonal anti-platelet antibody (MWReg30) intraperitoneally (ip, 18 h before TRALI induction) or intravenously (iv, 2 h before TRALI induction). In the active ITP model, SCID mice were transferred with splenocytes from anti-CD61 immune GPIIIa-knockout mice and thrombocytopenia occurred within 2 weeks post transfer (Chow et al Blood 115;1247, 2010). TRALI induction was performed by injecting the various thrombocytopenic SCID mice with a murine monoclonal MHC class I antibody (mAb, 34-1 -2s) iv and several parameters were observed for up to 2 h post antibody injection. In control, non-thrombocytopenic SCID mice, 34-1 -2s injection caused severe systemic shock as noted by reduced rectal temperatures which was associated with significant lung damage and mortality (45%) within 1 hour of 34-1 -2s infusion as previously shown (Fung et al. Blood DOI 10.1182/blood-2010-05-284570). In contrast, while SCID mice depleted of platelets by the passive ip route had systemic shock, lung damage and a 60% mortality rate, those mice made thrombocytopenic by the iv route were completely protected from mortality. On the other hand, in the active ITP model, where the induced thrombocytopenia is associated with a proinflammatory anti-platelet immune response, no mortality was observed in those mice made thrombocytopenic by antibody-mediated immune mechanisms whereas 80% of mice rendered thrombocytopenic by CD8+ T cell-mediated immunity were dead within 1 hr post 34-1 -2s infusion. These results suggest that thrombocytopenia in itself does not protect against antibody-mediated TRALI severity but the nature of the thrombocytopenia induction (e.g. acute passive iv infusion or active ITP immune transfer) is important. In fact, depending on the inflammatory milieu associated with the thrombocytopenia, platelets may actually increase the severity of TRALI. Disclosures: No relevant conflicts of interest to declare.