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Perfluorochemical (PFC) emulsions have been in development as intravenous oxygen carriers for a number of years and many publications have dealt with their oxygen transport characteristics in both experimental models and in clinical trials. Though it has been stressed on numerous occasions that PFCs deliver oxygen to the tissues in very different ways to those by which Hemoglobin (Hb) releases oxygen (O2), no serious attempts have been made to correlate the oxygen delivery capacity of PFCs to those of Hb. This paper presents theoretical ways in which this can be done and demonstrates that a 2.7 g/kg dose of PFC is approximately equivalent to 4 g/dL [Hb]. Clinical trial planning is discussed.

Four perfluorochemicals, Bis-[F-butyl]ethene, perfluorocyclohexylmorpholine, perfluorodecalin and perfluorooctylbromide were compared by their influence on the liver cytochrome P-450 system, measuring the pentobarbital sleeping time as defined by the time of loss of the righting reflex in rats. In all experiments first a prolongation of barbital detoxification was observed, which lasted at least 2-4 days. Thereafter a very long extended period of abbreviated sleeping time followed which was only missed after perfluoroctylbromide. Thus substrate competition, uncoupling of monooxygenation and enzyme induction determine the detoxifying processes in the liver that follow the administration of perfluorochemicals.

Exposure to hyperoxia, especially under hyperbaric conditions, causes an enhanced oxidative stress particularly in lung tissue. To test the potential hazardous effect of either a single or repeated hyperbaric oxygen treatment (HBO) on the cellular defence system the glutathione status of lung tissue from rats exposed to HBO was investigated. When daily exposed to 2.5 ATA of > 95% O2 for 90 min over 8 or 14 days the content of reduced glutathione in lung tissue (GSH) increased by 16-19%. Oxidized glutathione (GSSG) tended to increase after 8 days and was 56% higher after 14 days. While the GSSG/GSH ratio was unchanged after 8 days, it increased by 39% after 14 days. Thus, the GSH increase after 8 days can be understood as a adaptive process to protect the lung from oxidative stress. The distinct increment of the cellular GSSG that lead to an increase of the GSSG/GSH ratio after 14 days reflects a situation, in which the cellular defence system is overwhelmed by oxidative stress. The additional pretreatment with perfluorochemicals in a dose of 2g/kg every second day aggravated the observed changes (GSH +39-19%, GSSG +118%). In a second experiment rats were exposed to a single session with 7 ATA of O2 for 60 min. GSH in the lungs increased for 40%, it was not elevated by PFC. However, GSSG increased to a much higher degree in untreated as well as in PFC-treated animals (+240%, +163%), elevating the ratio GSSG/GSH markedly (+145%, +176%). Allopurinol given as radical scavenger in a dose of 50 mg/kg was able to suppress the increased oxidative stress widely. Thus adaptive and overloading processes are involved under the treatment with increased oxygen pressures. As the administration of PFC aggravates the observed changes, a still increased blood oxygen offer must be considered as the causative agent. A radical scavenger is capable to suppress the increased oxidative stress widely.

This paper has considered the effects and potential application of PFCs, their emulsions and emulsion components for regulating growth and metabolic functions of microbial, animal and plant cells in culture. PFCs will help to overcome problems encountered in conventional culture systems (e.g. limited gas supply, mechanical damage), especially where cells are grown to high density. While the commercial potential of PFCs for in vitro systems has not yet been fully exploited, the most exciting areas for future developments are in the culture of animal and plant cell lines of importance in biotechnology and medicine.

It is clear that the combination of 31P NMR studies of muscle and of other organs with biochemical and physiological measurements is an extremely powerful method for studying cellular energetics. We have presented examples of our on-going experiments. Well defined and stable in vitro preparations of mammalian fast-twitch (cat biceps) and slow-twitch (cat soleus) muscles are developed. Erythrocyte-containing perfusate is needed for adequate oxygenation during stimulation. It is not clear why fluorocarbon suspensions are inadequate. Inorganic phosphate levels in the fast-twitch biceps as determined from NRM spectra are close to lmM, that is very much lower than the value (6 mM) derived from chemical measurements of muscle extracts. A similar discrepancy in the slow-twitch soleus cannot yet be established; if it exists, the discrepancy is small. From the metabolite contents, the free energy available from ATP splitting is similar in both muscle types: -63 kJ/mole in biceps and -57 kJ/mole in soleus. Kinetic NMR measurements indicate the creatine phosphokinase reaction is at equilibrium, and in biceps the unidirectional fluxes are 5 mumole per gram per sec. Transient alkalinization of intracellular pH during stimulation periods and acidification during recovery periods are clearly seen. In the biceps the alkalinization is much smaller than in soleus, and suggests a greater buffer capacity in fast-twitch muscles. Both muscles recovery from prolonged ischemic periods upon reperfusion, although the recovery rate is very much slower than that from 10-20 min periods of stimulation in which similar decreases of PCr and increases of Pi occur. The pattern of recovery is however quite similar. Perfused muscles may be a useful model for studying ischemia, anoxia and hypoxia and are useful preparations for a wide variety of metabolic and energetic studies of fast-twitch and slow-twitch mammalian skeletal muscles.

Perfluoro-octylbromide-containing perfusate is capable of supporting the contractile activity of isolated hearts. Because of the high oxygen content of such perfusate, "normal" mechanical function is maintained by such hearts with substantially reduced coronary flow.

Previous work by the authors has shown that, following ligation of the left anterior descending coronary artery (LAD), myocardial oxygen tension (PmO2) in expected areas of maximal ischaemia is maintained at the expense of ischaemic border zones of the infarct area. Post-ischaemic haemodilution with the fluorocarbon containing plasma substitute Fluosol-DA 20% (FDA) could significantly improve PmO2 and pre-ischaemic haemodilution can delay myocardial ischaemia. We now present an analysis of the pattern of PmO2 changes to be seen when myocardial ischaemia is induced following prior haemodilution with FDA. Two groups of juvenile Yorkshire pigs were anaesthetised with intraperitoneal thiopentone, intubated and ventilated with halothane, nitrous oxide and oxygen. After placement of cardiovascular monitoring lines, a thoracotomy was performed. The pericardium was opened and 4 steel-protected gold microelectrodes were placed in the terminal supply area of the LAD in such a way that 2 electrodes were in the area of myocardial ischaema to be produced. One group of pigs were bled (20 ml/kg) and the loss was replaced with equal volumes of FDA. The animals were ventilated with halothane and oxygen and the terminal LAD was ligated. Electrode outputs were recorded on a flat bed recorder and analysed. LAD occlusion in the control animals resulted in similar changes in PmO2 to those described above.(ABSTRACT TRUNCATED AT 250 WORDS)