Cerebral oxygen delivery by liposome-encapsulated hemoglobin: a positron-emission tomographic evaluation in a rat model of hemorrhagic shock

2007 ◽  
Vol 103 (1) ◽  
pp. 28-38 ◽  
Author(s):  
Vibhudutta Awasthi ◽  
Seong-Hwan Yee ◽  
Paul Jerabek ◽  
Beth Goins ◽  
William T. Phillips
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Rat Model ◽  
Oxygen Delivery ◽  
Oxygen Metabolism ◽  
Blood Substitutes ◽  
Oxygen Carriers ◽  
Positron Emission Tomographic ◽  
Positron Emission

Liposome-encapsulated Hb (LEH) is being developed as an artificially assembled, low-toxicity, and spatially isolated Hb-based oxygen carrier (HBOC). Standard methods of evaluating oxygen carriers are based on surrogate indicators of physiology in animal models of shock. Assessment of actual delivery of oxygen by HBOCs and resultant improvement in oxygen metabolism at the tissue level has been a technical challenge. In this work, we report our findings from 15O-positron emission tomographic (15O-PET) evaluation of LEH in a rat model of 40% hypovolemic shock. In vitro studies showed that PEGylated LEH formulation containing ∼7.5% Hb and consisting of neutral lipids (distearoylphosphatidylcholine:cholesterol:α-tocopherol, 51.4:46.4:2.2) efficiently picks up 15O-labeled oxygen gas. The final preparation of LEH contained 5% human serum albumin to provide oncotic pressure. Cerebral PET images of anesthetized rats inhaling 15O-labeled O2 gas showed efficient oxygen-carrying and delivery capacity of LEH formulation. From the PET images, we determined cerebral metabolic rate of oxygen (CMRO2) as a direct indicator of oxygen-carrying capacity of LEH as well as oxygen delivery and metabolism in rat brain. Compared with control fluids [saline and 5% human serum albumin (HSA)], LEH significantly improved CMR[Formula: see text] to ∼80% of baseline level. Saline and HSA resuscitation could not improve hypovolemia-induced decrease in CMR[Formula: see text]. On the other hand, resuscitation of shed blood was the most efficient in restoring oxygen metabolism. The results suggest that 15O-PET technology can be successfully employed to evaluate potential oxygen carriers and blood substitutes and that LEH resuscitation in hemorrhage enhances oxygen delivery to the cerebral tissue and improves oxygen metabolism in brain.

S-nitroso human serum albumin given after LPS challenge reduces acute lung injury and prolongs survival in a rat model of endotoxemia

2008 ◽  
Vol 379 (3) ◽  
pp. 281-290 ◽  
Author(s):  
A. Jakubowski ◽  
N. Maksimovich ◽  
R. Olszanecki ◽  
A. Gebska ◽  
H. Gasser ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Human Serum Albumin ◽  
Lung Injury ◽  
Serum Albumin ◽  
Human Serum ◽  
Rat Model ◽  
Lps Challenge

S-Nitroso Human Serum Albumin Improves Oxygen Metabolism during Reperfusion after Severe Myocardial Ischemia

Pharmacology ◽  
2004 ◽  
Vol 72 (2) ◽  
pp. 106-112 ◽  
Author(s):  
Martin Dworschak ◽  
Maximilian Franz ◽  
Seth Hallström ◽  
Severin Semsroth ◽  
Harald Gasser ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Myocardial Ischemia ◽  
Serum Albumin ◽  
Human Serum ◽  
Oxygen Metabolism

scholarly journals Copolymerization of recombinant Phascolopsis gouldii hemerythrin with human serum albumin for use in blood substitutes

2016 ◽  
Vol 45 (2) ◽  
pp. 218-223 ◽  
Author(s):  
Mariann Arkosi ◽  
Florina Scurtu ◽  
Adriana Vulpoi ◽  
Radu Silaghi-Dumitrescu ◽  
Donald Kurtz
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Blood Substitutes

The biochemistry of drugs and doping methods used to enhance aerobic sport performance

2008 ◽  
Vol 44 ◽  
pp. 63-84 ◽  
Author(s):  
Chris E. Cooper
Keyword(s):  
Oxygen Uptake ◽  
Oxygen Content ◽  
Oxygen Delivery ◽  
Sport Performance ◽  
Blood Substitutes ◽  
Altitude Training ◽  
Blood Oxygen ◽  
Oxygen Carriers ◽  
Sports Performance ◽  
Blood Doping

Optimum performance in aerobic sports performance requires an efficient delivery to, and consumption of, oxygen by the exercising muscle. It is probable that maximal oxygen uptake in the athlete is multifactorial, being shared between cardiac output, blood oxygen content, muscle blood flow, oxygen diffusion from the blood to the cell and mitochondrial content. Of these, raising the blood oxygen content by raising the haematocrit is the simplest acute method to increase oxygen delivery and improve sport performance. Legal means of raising haematocrit include altitude training and hypoxic tents. Illegal means include blood doping and the administration of EPO (erythropoietin). The ability to make EPO by genetic means has resulted in an increase in its availability and use, although it is probable that recent testing methods may have had some impact. Less widely used illegal methods include the use of artificial blood oxygen carriers (the so-called ‘blood substitutes’). In principle these molecules could enhance aerobic sports performance; however, they would be readily detectable in urine and blood tests. An alternative to increasing the blood oxygen content is to increase the amount of oxygen that haemoglobin can deliver. It is possible to do this by using compounds that right-shift the haemoglobin dissociation curve (e.g. RSR13). There is a compromise between improving oxygen delivery at the muscle and losing oxygen uptake at the lung and it is unclear whether these reagents would enhance the performance of elite athletes. However, given the proven success of blood doping and EPO, attempts to manipulate these pathways are likely to lead to an ongoing battle between the athlete and the drug testers.

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