Lack of species specific difference in pulmonary function when using mouse versus human plasma in a mouse model of hemorrhagic shock.

Background: Clinical studies have demonstrated that the early and empiric use of plasma improves survival after hemorrhagic shock. We have demonstrated in rodent models of hemorrhagic shock that resuscitation with plasma is protective to the lungs compared to lactated Ringers. As our long term objective is to determine the molecular mechanisms that modulate plasma's protective effects in injured bleeding patients, we have used human plasma in a mouse model of hemorrhagic shock. The goal of the current experiments is to determine if there are significant adverse effects on lung injury when using human versus mouse plasma in an established murine model of hemorrhagic shock and laparotomy. Methods: Mice underwent laparotomy and 90 minutes of hemorrhagic shock to a mean arterial pressure of 35+/-5 mm Hg followed by resuscitation at 1x shed blood using either mouse fresh frozen plasma (FFP), human fresh frozen plasma or human lyophilized plasma. Mean arterial pressure (MAP) was recorded during shock and for the first 30 minutes of resuscitation. After 3 hours, animals were euthanized and lungs collected for analysis. Results: There was a significant increase in early MAP when mouse FFP was used to resuscitate animals compared to human FFP or human lyophilized plasma. However in spite of these differences, analysis of the mouse lungs revealed no significant differences in pulmonary histopathology, lung permeability or lung edema between all three plasma groups. Analysis of neutrophil infiltration in the lungs revealed that mouse FFP decreased neutrophil influx as measured by neutrophil staining, however myeloperoxidase immunostaining revealed no significant differences in between groups. Conclusions: The study of human plasma in a mouse model of hemorrhagic shock is feasible, but does reveal some differences compared to mouse plasma-based resuscitation in physiologic measures such as MAPs post-resuscitation. Measures of end organ function such as lung injury appear to be comparable in this acute model of hemorrhagic shock and resuscitation. Level of evidence: NA (C) 2016 Lippincott Williams & Wilkins, Inc.

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