title: A novel nanobiotherapeutic poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase] with no cardiac toxicity for the resuscitation of a rat model with 90 minutes of sustained severe hemorrhagic shock with loss of 2/3 blood volume.
abstract: We crosslink hemoglobin (Hb), superoxide dismutase (SOD), catalase (CAT), and carbonic anhydrase (CA) to form a soluble polyHb-SOD-CAT-CA nanobiotechnological complex. The obtained product is a soluble complex with three enhanced red blood cell (RBC) functions and without blood group antigens. In the present study, 2/3 of blood volume was removed to result in 90-min hemorrhagic shock at mean arterial blood pressure (MAP) of 30 mmHg. This was followed by the reinfusion of different resuscitation fluids, then followed for another 60 min. PolyHb-SOD-CAT-CA maintained the MAP at 87.5 ± 5 mmHg as compared with 3 volumes of lactated Ringer's solution, 43.3 ± 2.8 mmHg; blood, 91.3 ± 3.6 mmHg; polyHb-SOD-CAT, 86.0 ± 4.6 mmHg; poly stroma-free hemolysate (polySFHb), 85.0 ± 2.5 mmHg; and polyHb, 82.6 ± 3.5 mmHg. PolyHb-SOD-CAT-CA was superior to the blood and other fluids based on the following criteria. PolyHb-SOD-CAT-CA reduced tissue pCO2 from 98 ± 4.5 mmHg to 68.6 ± 3 mmHg. This was significantly (p < 0.05) more effective than lactated Ringer's solution (98 ± 4.5 mmHg), polyHb (90.1 ± 4.0 mmHg), polyHb-SOD-CAT (90.9 ± 1.4 mmHg), blood (79.1 ± 4.7 mmHg), and polySFHb (77 ± 5 mmHg). PolyHb-SOD-CAT-CA reduced the elevated ST level to 21.7 ± 6.7% and is significantly (< 0.05) better than polyHb (57.7 ± 8.7%), blood (39.1 ± 1.5%), polySFHb (38.3% ± 2.1%), polyHb-SOD-CAT (27.8 ± 5.6%), and lactated Ringer's solution (106 ± 3.1%). The plasma cardiac troponin T (cTnT) level of polyHb-SOD-CAT-CA group was significantly (P < 0.05) lower than that of all the other groups. PolyHb-SOD-CAT-CA reduced plasma lactate level from 18 ± 2.3 mM/L to 6.9 ± 0.3 mM/L. It was significantly more effective (P < 0.05) than lactated Ringer's solution (12.4 ± 0.6 mM/L), polyHb (9.6 ± 0.7 mM/L), blood (8.1 ± 0.2 mM/L), polySFHb (8.4 ± 0.1 mM/L), and polyHb-SOD-CAT (7.6 ± 0.3 mM/L). PolyHb-SOD-CAT-CA can be stored for 320 days at room temperature. Lyophilized poly-Hb-SOD-CAT-CA can be heat pasteurized at 68F for 2 h. This can be important if there is a need to inactivate human immunodeficiency virus, Ebola virus, and other infectious organisms.
authors.affiliation: Artificial Cells and Organs Research Centre, Departments of Physiology, Medicine and Biomedical Engineering, Faculty of Medicine, McGill University , Montreal, QC , Canada.
authors.forename: Yuzhu
authors.initials: Y
authors.lastname: Bian
authors.forename: Thomas Ming Swi
authors.initials: TM
authors.lastname: Chang
mesh_terms: D000818:Animals; D001692:Biological Transport; D001794:Blood Pressure / Q000187:drug effects; D001802:Blood Substitutes / Q000737:chemistry / Q000494:pharmacology*; D001810:Blood Volume; D002245:Carbon Dioxide / Q000097:blood; D002256:Carbonic Anhydrases / Q000737:chemistry / Q000494:pharmacology*; D002374:Catalase / Q000737:chemistry / Q000494:pharmacology*; D003432:Cross-Linking Reagents / Q000737:chemistry; D004195:Disease Models, Animal; D004355:Drug Stability; D005440:Fluid Therapy; D005612:Freeze Drying; D005976:Glutaral / Q000737:chemistry; D006454:Hemoglobins / Q000737:chemistry / Q000494:pharmacology*; D007552:Isotonic Solutions / Q000008:administration & dosage; D019344:Lactic Acid / Q000097:blood; D010100:Oxygen / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation / Q000379:methods; D000077325:Ringer's Lactate; D012771:Shock, Hemorrhagic / Q000097:blood / Q000503:physiopathology / Q000628:therapy*; D013482:Superoxide Dismutase / Q000737:chemistry / Q000494:pharmacology*; D020107:Troponin T / Q000097:blood
chemical_list: D001802:Blood Substitutes; D003432:Cross-Linking Reagents; D006454:Hemoglobins; D007552:Isotonic Solutions; D000077325:Ringer's Lactate; D020107:Troponin T; D002245:Carbon Dioxide; D019344:Lactic Acid; D002374:Catalase; D013482:Superoxide Dismutase; D002256:Carbonic Anhydrases; D010100:Oxygen; D005976:Glutaral
keywords: antioxidant; artificial cells; biotherapeutic; carbon dioxide carrier; carbonic anhydrase; cardiac toxicity; catalase; hemorrhagic shock; inactive infectious agents; ischemia–reperfusion; oxygen carrier; oxygen radicals; pasteurization; resuscitation; storage stability; superoxide dismutase