title: Characterization of hemodynamic, hematologic, and biochemical responses to administration of liposome-encapsulated hemoglobin in the conscious, freely moving rat.
abstract: To improve the outcome of trauma victims and of patients undergoing high-blood-loss surgical procedures and to avoid the many serious complications of blood transfusion, there is a need for an oxygen-carrying blood substitute. Synthetic erythrocytes composed of liposome-encapsulated hemoglobin (LEH) represent one of the significant research efforts in this direction. The purpose of the present study was to examine some of the cardiovascular, hematologic, and biochemical effects of a recently developed LEH preparation in the conscious rat (n = 7). LEH increased mean arterial pressure (MAP) by +18.7 +/- 4.7 mm Hg (P less than 0.01) and heart rate (HR) by +117 +/- 18 beats/min (P less than 0.05). Platelet count dropped to 40% of basal value (P less than 0.01), while plasma thromboxane B2 (TXB2) increased by +25.1 +/- 5.4 pg/100 microliters (P less than 0.001). There was no effect on plasma 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha). Hemoglobin and hematocrit levels were elevated as well as the white blood cell count [( WBC] lymphocytosis). The platelet and TXB2 responses to LEH showed negative correlation (R = -0.56, P less than 0.01). The injection of the liposome vehicle (LIP) decreased MAP by -16.5 +/- 5.1 mm Hg (P less than 0.01) and platelets, but increased HR, WBC, and TXB2. All observed effects exerted by LEH and LIP were transient, and basal levels obtained 120 min after LEH injection. These data suggest that while LEH maintains some physicochemical properties of red blood cells, its biological properties at the present time indicate potential cardiovascular and hematological liabilities. Furthermore, it seems that the phospholipid bilayer alone or in combination with free Hb might be responsible for the biological effects of LEH.
authors.affiliation: Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799.
authors.forename: R
authors.initials: R
authors.lastname: Rabinovici
authors.forename: A S
authors.initials: AS
authors.lastname: Rudolph
authors.forename: G
authors.initials: G
authors.lastname: Feuerstein
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood*; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects*; D001802:Blood Substitutes / Q000032:analysis / Q000138:chemical synthesis / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D006400:Hematocrit; D007962:Leukocytes / Q000187:drug effects; D008081:Liposomes / Q000494:pharmacology; D008297:Male; D010976:Platelet Count / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013929:Thromboxane B2 / Q000097:blood*; D013997:Time Factors
chemical_list: D001802:Blood Substitutes; D008081:Liposomes; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha