title: Nanovesicular liposome-encapsulated hemoglobin (LEH) prevents multi-organ injuries in a rat model of hemorrhagic shock.
abstract: The goals of resuscitation in hemorrhagic shock are to correct oxygen deficit and to maintain perfusion pressure to the vital organs. We created liposome-encapsulated hemoglobin (LEH) as a nanoparticulate oxygen carrier (216±2nm) containing 7.2g/dl hemoglobin, and examined its ability to prevent the systemic manifestations of hemorrhagic shock (45% blood loss) in a rat model. We collected plasma after 6h of shock and LEH resuscitation, and determined the circulating biomarkers of systemic inflammation and functions of liver, gut, heart, and kidney. As is typical of the shock pathology, a significant increase in the plasma levels of cardiac troponin, liver function enzymes, soluble CD163 (macrophage activation), and creatinine, and the liver/gut myeloperoxidase activity was observed in the hemorrhaged rats. The plasma levels of TNF-α, IL-6, IL-1α, CINC-1, and IL-22 also increased after hemorrhagic shock. LEH administration prevented the hemorrhagic shock-induced accumulation of the markers of injury to the critical organs and pro-inflammatory cytokines. LEH also decreased the plasma levels of stress hormone corticosterone in hemorrhaged rats. Although saline also reduced the circulating corticosterone and a few other tissue injury markers, it was not as effective as LEH in restraining the plasma levels of creatinine, alanine transaminase, CD163, TNF-α, IL-6, and IL-1α. These results indicate that resuscitation with nanoparticulate LEH creates a pro-survival phenotype in hemorrhaged rats, and because of its oxygen-carrying capacity, LEH performs significantly better than saline in hemorrhagic shock.
authors: Department of Pharmaceutical Sciences, University of Oklahoma Health Science Center, 1110 N. Stonewall Avenue, Oklahoma City, OK 73117, USA.
authors: Vivek R
authors: VR
authors: Yadav
authors: Department of Pharmaceutical Sciences, University of Oklahoma Health Science Center, 1110 N. Stonewall Avenue, Oklahoma City, OK 73117, USA.
authors: Geeta
authors: G
authors: Rao
authors: Department of Pharmaceutical Sciences, University of Oklahoma Health Science Center, 1110 N. Stonewall Avenue, Oklahoma City, OK 73117, USA.
authors: Hailey
authors: H
authors: Houson
authors: Department of Pharmaceutical Sciences, University of Oklahoma Health Science Center, 1110 N. Stonewall Avenue, Oklahoma City, OK 73117, USA.
authors: Andria
authors: A
authors: Hedrick
authors: Department of Pharmaceutical Sciences, University of Oklahoma Health Science Center, 1110 N. Stonewall Avenue, Oklahoma City, OK 73117, USA.
authors: Shanjana
authors: S
authors: Awasthi
authors: Department of Anesthesiology, University of Oklahoma Health Science Center, 750 N.E. 13th St., Oklahoma City, OK 73104, USA.
authors: Pamela R
authors: PR
authors: Roberts
authors: Department of Pharmaceutical Sciences, University of Oklahoma Health Science Center, 1110 N. Stonewall Avenue, Oklahoma City, OK 73117, USA. Electronic address: Vibhudutta-Awasthi@ouhsc.edu.
authors: Vibhudutta
authors: V
authors: Awasthi
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006454:Hemoglobins / Q000008:administration & dosage*; D008081:Liposomes; D036103:Nanotechnology; D051381:Rats; D012771:Shock, Hemorrhagic / Q000517:prevention & control*
chemical_list: D006454:Hemoglobins; D008081:Liposomes
keywords: Hemorrhagic shock; Inflammation; Liposome-encapsulated hemoglobin; Nanoparticle; Organ injury; Resuscitation