Effect of Artificial Oxygen Carrier with Chemotherapy on Tumor Hypoxia and Neovascularization

Liposome-encapsulated hemoglobin (LHb), which is structurally similar to red blood cells (RBC) except smaller size (250 nm), can serve as blood substitute comparable to RBC. We have reported that intraosseous blood infusion (IOI) is effective treatment in shock mice model. IOI is alternative to peripheral i.v. infusion and is expected as an important field treatment in civilian emergency because of no collapse of intramedullary blood vessels in the bone marrow in shock. However, we did not evaluate the side effects of LHb in IOI. Total 70% hemorrhagic shock was induced by femoral vein bleeding. Immediately after bleeding, 17 mice were resuscitated with tibial bone IOI of 5% albumin (5% albumin), 18 mice resuscitated with mouse-washed RBC (Wash RBC) and 14 mice resuscitated with LHb (LHb-group). Survival rates were compared and the temporal changes in cytokins (TNF, INFγ) as well as liver and renal function (s-ALT, s-creatinine) were measured. All mice survived 48 h after IOI of LHb whereas only 47% and 45% mice survived in 5% albumin and Wash RBC, respectively (Fig. 1 ). The changes in TNF and INFγlevels after IOI were not statistically different among 3 groups (Fig. 2 ) and no side effects were found on liver and renal function.. Conclusions: LHb has a better anti-shock effect than RBC by using IOI probably due to smaller size and IOI of LHb could be useful in disaster medicine. In addition, IOI of LHb shows no significant effects on cytokins, liver and renal function. Figure 1 Figure 2

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Uridine regulation by the isolated rat liver: perfusion with an artificial oxygen carrier

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1982.242.5.r465 ◽

1982 ◽

Vol 242 (5) ◽

pp. R465-R470 ◽

Cited By ~ 2

Author(s):

A. Monks ◽

R. L. Cysyk

Keyword(s):

Rat Liver ◽

Oxygen Carrier ◽

Liver Perfusion ◽

Blood Substitute ◽

Rat Plasma ◽

Perfusion Medium ◽

Artificial Oxygen Carrier ◽

Isolated Rat Liver ◽

Rat Liver Perfusion ◽

Isolated Rat

The isolated rat liver was used to investigate the role of the liver in the regulation of circulating uridine concentrations. A synthetic blood substitute (Fluosol-43) was utilized as an alternative oxygen-carrying perfusion medium to a simplified blood preparation and produced no apparent hepatotoxicity within the perfusion period. The isolated rat liver excreted uridine into a circulating perfusion medium achieving concentrations similar to those found in rat plasma (1.4 +/- 0.6 microM). The mean output of uridine over 2 h was 107 nmol.h-1.g liver-1, but if the perfusate was recirculated the net output of uridine was reduced to 12.7 nmol.h-1.g-1. The rate of depletion of nonphysiological concentrations of circulating uridine was found to be concentration dependent up to 25 microM. At a steady state of circulating uridine, a radioactive uridine spike was cleared with a half-life of 7.4 min and an elimination constant of 0.094 min-1; 30% of the radioactivity appeared in the perfusate as metabolites of uridine within 40 min. Thus the perfused rat liver acts to maintain circulating uridine concentrations similar to those measured in plasma.

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Artificial oxygen carrier based on polysaccharides–poly(alkylcyanoacrylates) nanoparticle templates

Biomaterials ◽

10.1016/j.biomaterials.2010.04.039 ◽

2010 ◽

Vol 31 (23) ◽

pp. 6069-6074 ◽

Cited By ~ 25

Author(s):

Cédric Chauvierre ◽

Romila Manchanda ◽

Denis Labarre ◽

Christine Vauthier ◽

Michael C. Marden ◽

...

Keyword(s):

Oxygen Carrier ◽

Artificial Oxygen Carrier

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Perflubron Emulsion in Prolonged Hemorrhagic Shock

Anesthesiology ◽

10.1097/00000542-200306000-00014 ◽

2003 ◽

Vol 98 (6) ◽

pp. 1391-1399 ◽

Cited By ~ 26

Author(s):

Markus Paxian ◽

Hauke Rensing ◽

Katrin Geckeis ◽

Inge Bauer ◽

Darius Kubulus ◽

...

Keyword(s):

Gene Expression ◽

Glutamine Synthetase ◽

Adenosine Triphosphate ◽

Oxygen Supply ◽

Oxygen Carrier ◽

Oxygen Availability ◽

Oxygen Carriers ◽

Hepatocellular Injury ◽

Artificial Oxygen Carrier ◽

Stored Blood

Background Liver dysfunction as a result of impaired oxygen availability frequently occurs following hemorrhage and contributes to delayed mortality. Artificial oxygen carriers may improve oxygen supply to vital organs while avoiding the need for allogeneic transfusion. Methods Rats were subjected to hemorrhagic hypotension (mean arterial pressure = 35-40 mmHg for 120 min) and were subsequently resuscitated with (1) stored whole rat blood, (2) pentastarch, or (3) pentastarch combined with perflubron emulsion (PFE; 2.7 or 5.4 g/kg body weight), a second-generation artificial oxygen carrier. Recovery of liver adenosine triphosphate, hepatocellular injury, and expression of glutamine synthetase 1, a gene that is induced by exposure of hepatocytes to low partial pressure of oxygen, were studied at 4 h of resuscitation. Results Stored whole blood or pentastarch failed to restore liver adenosine triphosphate concentrations after prolonged shock as compared to sham controls and resulted in increased gene expression of glutamine synthetase 1. Addition of 2.7 g PFE/kg restored liver adenosine triphosphate to control, whereas 5.4 g PFE/kg resulted in adenosine triphosphate concentrations significantly above control. Improved hepatocellular oxygen supply was also confirmed by restoration of the physiologic expression pattern of glutamine synthetase 1. Serum enzyme concentrations were highest after resuscitation with stored blood, whereas addition of PFE failed to further decrease enzyme concentrations as compared to pentastarch alone. Conclusions Resuscitation with PFE is superior to stored blood or asanguineous resuscitation with respect to restoration of hepatocellular energy metabolism. The improved hepatocellular oxygen availability is reflected in normalization of oxygen-dependent gene expression. However, improved oxygen availability failed to affect early hepatocellular injury.

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