What are the first-generation blood substitutes?

Updated: Dec 11, 2018
  • Author: Sara J Grethlein, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Perfluorocarbons are chemically inert molecules containing primarily, as the name suggests, fluorine and carbon atoms. They are capable of dissolving large amounts of many gases, including oxygen. These molecules are hydrophobic in nature, and hence have to be emulsified prior to intravenous administration. [4]

After intravenous administration, the droplets of this emulsion are taken up by the reticuloendothelial system and then slowly broken down. They are then transported to blood, where they are bound to lipids and move to the lungs. In the absence of significant in vivo metabolism, perfluorocarbons are removed from the body by exhalation.

Perfluorocarbons demonstrate a linear oxygen dissociation curve in contrast to the sigmoid dissociation curve of blood. Hence, elevated arterial partial pressures of oxygen enhance oxygen transport by these molecules. However, this linear relationship can also work as a disadvantage since most of the oxygen is released prior to the arrival of the oxygen-laden molecule in the capillary network where the partial pressure of oxygen is lower, and hence the need for oxygen is greater.

Among the various perfluorocarbon emulsions that have been developed are the molecules perfluorooctyl bromide (perflubron), perfluorodecyl bromide, and perfluorodichlorooctane. [5]

The first product to be marketed contained perfluorodecalin and perfluorotripropylamine emulsified with Pluronic F-68 and called Fluosol-DA. It was manufactured by the Green Cross Corporation (Japan) and Alpha Therapeutics (Grifols USA, Los Angeles, Calif). It was approved by the FDA for use in percutaneous transluminal coronary angioplasty. However, due to marginal efficacy, a short effective half-life, temperature instability, low oxygen-carrying capacity, and adverse effects such as acute complement activation and disruption of pulmonary surfactant, this product has since been withdrawn from the market.

A more stable emulsion containing 58% weight per volume perfluorooctyl bromide and 2% weight per volume perfluorodecyl bromide emulsified in 3.6% weight per volume egg yolk phospholipid concentrated to 60% weight per volume was then developed by Alliance Pharmaceutical Corporation (San Diego, Calif). With greater stability at room temperature than Fluosol-DA and with an increased oxygen carrying capacity (4-5 times greater than Fluosol-DA) this compound, called Oxygent, showed great promise initially. However, phase III trials showed an increased incidence of stroke in treated patients compared to controls and trials have been halted. [6]

Other PFC emulsions that have been developed include Perftoran (Perftoran, Moscow, Russia; also registered and in use in Mexico under the trade name Perftec), Oxycyte (Synthetic Blood International, Costa Mesa, Calif; entering phase II trials), and Oxyfluor (HemaGen/perfluorocarbon, St Louis, Mo; discontinued due to safety issues). [7]

A study by Johnson et al indicated that dodecafluoropentane may be an effective oxygen-delivery agent for the treatment of hypoxic medical conditions. [5] In an in vitro comparison of 2% weight per volume emulsions of dodecafluoropentane, perfluorodecalin, and perfluorooctyl bromide, the investigators found that at 21º C, dodecafluoropentane absorbed 3 times more oxygen than did the other 2 agents, and that at 37º C, it absorbed 7 times more oxygen. [5]

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