Daniel Freilich, Fred Apple, Todd Johnson, Matthew Warndorf, Nora Philbin, Ludmila Asher, W. S. Flournoy, Lewis J. Kaplan, Gerald McGwin, Jennifer Rice, Jennifer M. Gurney, Stephen T. Ahlers, Martin Arrisueno, Francoise Arnaud, Feng Dong, Richard M. McCarron, and Lesly A. Pearce
Objective: To test our hypothesis that hemoglobin-based oxygen carrier (HBOC)-201 resuscitation in hemorrhagic shock (HS) will not lead to increased organ injury and dysfunction. Design: Three swine HS models simulating military-relevant delayed evacuation: a) moderate controlled HS, b) severe controlled HS, and c) severe uncontrolled HS. Setting: Military research laboratory. Subjects: Swine. Interventions: Swine were anesthetized/intubated and instrumented. To induce HS, in two controlled hemorrhage experiments, 40% (moderate controlled HS) or 55% (severe controlled HS) of blood volume was withdrawn; in an uncontrolled HS experiment, the liver was crushed/lacerated. During a 4-hr "prehospital phase," pigs were resuscitated with HBOC-201 (HBOC) or Hextend (HEX) or were non-resuscitated (NON). Upon "hospital arrival," liver injury was repaired (severe uncontrolled HS), blood or saline was infused, hemodynamics were monitored, and blood was collected. Upon animal death and/or 72 hrs, necropsy was followed by histopathologic evaluation of organ injury (hematoxylin and eosin, electron microscopy) and immunohistochemistry of oxidative potential (3-nitrotyrosine). Significance (p