The first real success in fluid breathing came in 1966, with Dr. Leland Clark's "liquid-breathing-mouse" experiment. Dr. Clark (inventor of the Clark electrode) realized that oxygen and carbon dioxide were very soluble in fluorocarbon liquids (like freon). Assuming that the alveoli of the lungs should be capable of drawing oxygen out of the fluid and replacing it with carbon dioxide, Clark suggested that these fluorocarbons should support respiration of animals. Performing the first tests on anaesthetized mice, Dr. Clark temporarily paralyzed each intubated animal, inflating a cuff inside the trachea to provide a seal and ensure that no air entered the lungs, and no solution leaked out.



After bubbling oxygen through the fluorocarbon, the oxygenated fluid was pumped into the animals' lungs, and recirculated (about 6 cycles of inhalation and exhalation per minute). Most of the animals who were kept in the fluid for up to an hour survived for several weeks after their removal, before eventually succumbing to pulmonary damage. Autopsies uniformly revealed that the lungs appeared congested when collapsed but normal when inflated. Some of the early problems Clark encountered seemed to be due to the size of the animals' airway. The tiny size physically limited the amount of fluid that could get into the lungs. For that and other reasons, carbon dioxide tended to build up in the system: it simply couldn't be removed fast enough.



This photograph demonstrates a living mouse breathing in the liquid, while a goldfish inhabits the water floating on top.



Dr. Clark discovered that the length of time the mice could survive in the fluid was directly related to the fluorocarbon's temperature: the colder the fluid, the lower the respiration rate which in turn prevented carbon dioxide buildup. He therefore induced hypothermia in the animals. This technique seemed to give the most success, as one animal survived over 20 hours breathing fluid at 18oC. Purified haemoglobin This is produced from expired red blood cells, for example diaspirin cross-linked haemoglobin. Recombinant haemoglobin This is a modified human haemoglobin tetramer cross-linked with a glycine bridge between the alpha subunits. It is produced from Escherichia Coli or yeast. The cross-links prevent renal excretion. The haemoglobin solutions must be free of red cell debris to avoid renal damage. Other effects include impairment of macrophage activity. These products are hyperosmotic and are quickly broken down in the blood. The oxygen dissociation curve is shifted to the left with use of these products. Bovine haemoglobin has also been used. Perfluorocarbons These are inert chemicals with oxygen solubility 20X that of plasma. They exist as a 10% solution. These solutions carry dissolved oxygen in an amount directly proportional to its partial pressure. its accumulation in the reticulo-endothelial system is at present, of unknown significance.

ArticleDate:20041202

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