Synthetic Oxygen Transport Fluids Based on Perfluorochemicals: Applications in Medicine and Biology

Abstract

Recent advances in the development and assessment of synthetic oxygen transport fluids based on perfluorochemicals (PFCs) are reviewed. The basic properties of PFCs are outlined, together with the selection criteria for biomedical applications. PFCs must be emulsified for intravascular use and attention is focussed on the formulation and biocompatibility testing of both first- and second-generation emulsions and their components in man and other species. The multidisciplinary applications for PFCs in medicine and basic biomedical research are described, including the clinical use of Fluosol-DA 20% as an oxygen-carrying perfusate in percutaneous transluminal coronary angioplasty.

Uptake of Concentrated Perfluorocarbon Emulsions into Rat Lymphoid Tissues

“…Perfluorochemical (PFC) emulsions are attracting increasing interest for biomedical uses as, for example, vehicles for respiratory gas transport and contrast agents for diagnostic tissue imaging (Lowe 1988a(Lowe , 1991(Lowe , 1992. PFCs are considered as chemically inert owing to the high strength of the carbon-fluorine bond (ca.…”

“…Much of the previously published work in this area has been concerned with biological studies using emulsions containing approximately 20% (w/v) of the PFC component (Lowe 1988b). The most widely tested emulsion of this type is the proprietary formulation, Fluosol (Green Cross, Japanavailable in the UK through Alpha Therapeutic, Thetford), which has recently been approved both in the UK and USA for myocardial oxygenation during angioplasty (Lowe 1991(Lowe , 1992. The use of formulations containing an increased PFC phase fraction would, in principle, improve the performance of these materials.…”

Fluorocarbon emulsions

“…A low incidence of minor side-effects, such as chest tightness and flushing, were described, as was an increase in leucocytes during the first week. There was a reduction in the platelet count at 24 hours, but no effect on the bleeding time. Fibrinogen levels were reduced with prolongation of some tests of clot lysis.…”

“…In a series of studies using a stroke model of cats undergoing permanent or temporary middle cerebral artery (MCA) occlusion for four hours followed by a period of blood reperfusion, animals treated with 15 ml/kg Fluosol DA 35% and breathing 95% oxygen showed initial benefit in terms of improved recovery of neurological function compared with controls treated with mannitol or saline, but this benefit did not persist beyond six hours after reperfusion or following permanent ligation.140 There was some suggestion that Fluosol treatment caused deterioration in the presence of reperfusion by increasing cerebral oedema. However, subsequent ultrastructural studies showed that Fluosol administration following permanent MCA occlusion was associated with less evidence of structural damage 24 showed that although Fluosol administration in cats was associated with improved tissue oxygen availability in normally perfused brain, this fell to the same level as the controls during ischaemia (MCA occlusion) and that, although blood flow following reperfusion was increased, there was no functional or ultrastructural difference observed. 142 Fluosol (20 ml/kg) infused in dogs intravenously has been shown to improve functional recovery from spinal cord ischaemia following aortic crossclamping, although Fluosol infusion was associated with a higher mean distal aortic pressure during the period of crossclamping, which may have been protective.…”

“…56 There is contradictory evidence of alteration of metabolic activity in the liver following Fluosol administration. 24 In animal models, biliary excretion of drugs, hepatic blood flow and microsomal activity have been affected,57,58 but there is no evidence of this being of significance in the human studies of fluorocarbon treatment. However, the presence of fluorocarbon emulsion in plasma has been noted to interfere with assays of heparin activitys9 and to displace warfarin60 and other drugs61 from albumin binding sites.…”