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

Abstract

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. After exposure to standard room light or to intense light (10000 LUX), mice were hemorrhaged for 90minutes to maintain a mean arterial pressure (MAP) of 30-35mmHg. Mice were then resuscitated with their blood and a NaCl infusion at a rate of 0.2ml/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. 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. 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.