Administration Of Perfluorochemicals Research Articles

Cerebral Oxygenation Is Affected by Filling Mode and Perfluorochemical Volume in Partial Liquid Ventilation of Healthy Piglets

Intrapulmonary administration of perfluorochemicals (PFC) has been suggested for reasons other than respiratory insufficiency. PFC application has been described to affect cerebral Hb concentration, however, data for healthy lungs are missing. Newborn piglets were randomized into 3 groups (30-ml slow-filling, 10-ml slow-filling and 30-ml rapid-filling), orally intubated and mechanically ventilated. Partial liquid ventilation (PLV) was initiated by filling the lung with PF5080 (10 or 30 ml/kg) at a rate of 1.5 ml/min (slow filling) or within 45 s (rapid filling). Vital signs, blood gases, tidal volume (VT) and changes in the cerebral concentration of oxygenated hemoglobin (HbO₂) and total Hb were determined for up to 20 min. Rapid administration of PFC caused an immediate drop in HbO₂, PaO₂ and VT. The concentration of oxygenated and total Hb increased thereafter and remained high. We found a slow increase in PaCO₂, HbO₂ and total Hb in the 30-ml slow-filling group, but almost no changes in the 10-ml slow filling group (except for a decrease in PaO₂). According to our data, PLV with 10 ml/kg should be preferred since cerebral alterations are minimal. If complete filling of the lung is needed PFC should be administered slowly to minimize side effects.

Administration of perfluorochemicals under hyperbaric oxygen pressure and treatment with free oxygen radical scavengers.

A combination of increased oxygen pressure and the administration of perfluorochemicals (PFC) may be useful in tumor radiation therapy, where hypoxic areas of tissue are less sensitive to the application of an energy rich treatment. Though oxygen pressures of some ten mm Hg like those at the venous end of capillaries seem to be sufficient for radiosensitivity of tumor cells, this level is not realized in many tumor zones [I-61. Mueller-Klieser et al. [6] found a disappearance of red blood cells with an oxygen saturation below 5 96 in tumor blood vessels only under a hyperbaric pressure of 4 ATA (atmospheres of absolute pressure; 1 ATAcJ1OO kPa) in contrast to the observation at 3 ATA. Oxygen pressures up to 4 and 5 ATA were also used for oxygenation of tumors by several authors [I-3,7]. The reason that such high pressures of oxygen are needed may be the occurrence of vasoconstriction (usually seen at elevated oxygen pressures) which must be overcome by larger pressures. Thus either very high oxygen pressures - which however will rapidly reach the safe limits even for short lasting oxygen therapy or improved oxygen transport to tissues are desirable conditions for a more successful radiation treatment. While some studies on radiation treatment, utilizing the combination of PFC with a normotonic oxygen- or carbogen environment have been described [8-91, the combination of PFC with hyperbaric oxygen in the above mentioned pressure ranges may involve further problems. Geyer [lo] reported from preliminary results that the development of convulsions in rats whose blood was totally exchanged by PFC did appear more than 10 times earlier than in controls at an oxygen pressure of 2 ATA, and still 4.5 - 5 times earlier in those animals with only partial blood exchange. However, when survival time was utilized as a criterion of toxicity, rats receiving 8 g PFC/kg body weight (b.w.) demonstrated only a moderate diminution of their survival times compared to controls when exposed to 2.6 - 6.8 ATA of oxygen pressure in our previous experiments [I I]. We are now reporting the results of a more detailed investigation. In these studies in addition to survival time we utilized the time period to the onset of convulsions as well as the increase in wet weight of the lungs of rats as criteria of toxicity. One further goal of this study was to explore whether the sensitizing effect of PFC could be counteracted by the administration of free oxygen radical scavengers.

Survival time of rats exposed to different high oxygen pressures after administration of perfluorochemicals.

Hyperbaric oxygen administration is considered useful in the treatment of anaerobic infections (Cline and Turnbull, 1985) as well as in tumour radiation therapy (Fischer, Rockwell and Martin, 1986) where very high tissue partial pressures of oxygen are needed. The most commonly used oxygen pressure of 300 kPa (3 ATA) may not be sufficient to reach this goal. There must be sufficient oxygen capacity in the blood to maintain an elevated partial pressure even at the venous end of capillaries when oxygen is consumed. More effective treatment could be accomplished if haemoglobin were to remain in the oxygenated form. The administration of perfluorochemicals (PFC) which increase the oxygen capacity under elevated oxygen partial pressure can help in attaining this goal. However, as judged from previous results obtained by Geyer (1983), hyperbaric oxygen treatment combined with PFC administration can be expected to augment oxygen toxicity considerably. To test this supposition hyperbaric oxygen was applied and survival times were measured in rats as an index of the overall tolerance of the organism at various oxygen pressures. Survival time was found to give a more precise endpoint than the determination of the onset of convulsions. It was the goal of this study to establish the relationship between oxygen tension and lethal duration of exposure in both control and PFC-treated animals.

Long term experiment of perfluorochemicals using rabbits.

Morphological changes six months of two years after the administration of Perfluorochemicals (PFC) in rabbits injected with a large amount of PFC (67 mg/kg) have already been reported by Ohnishi and Kitazawa (1979, 1980, and 1981). In this paper, the authors report on the persistence of large numbers of foamy cells in the liver, spleen and lymph nodes and many in the kidneys, lung and bone marrow, up to two years after administration. Quantitative analysis of PFC in various organs showed that it was retained. The liver revealed progressive fibrosis surrounding the foamy cells in or around the Glisson's sheath.