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

作者：Bian Yuzhu; Chang Thomas Ming Swi^*

来源：Artificial Cells, Nanomedicine and Biotechnology, 2015, 43(1): 1-9.

DOI：10.3109/21691401.2014.964554

• artificial cells
• antioxidant
• biotherapeutic
• catalase
• carbon dioxide carrier
• carbonic anhydrase
• cardiac toxicity
• hemorrhagic shock
• inactive infectious agents
• ischemia-reperfusion
• oxygen carrier
• oxygen radicals
• pasteurization
• resuscitation
• superoxide dismutase
• storage stability

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 pCO(2) 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.

• 出版日期2015-2