Fluid breathing
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Liquid breathing is a form of respiration in which someone breathes an oxygen rich liquid (usually from the perfluorocarbon family), rather than breathing air. It is used for medical treatment and for deep sea diving.
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The early experiments
In the mid 1960's Dr. J. Kylstra, a physiologist at the State University of New York at Buffalo, realized that salt solutions could be saturated with oxygen at high pressures. In a US Navy recompression chamber, Kylstra experimented to see if mice could move the saline solution in and out of their lungs, while extracting enough oxygen from the fluid to survive. The mice and rats could breathe the liquid (he could keep the animals alive for up to 18 hours), but carbon dioxide was not removed fast enough from the system, and quickly built up to near-toxic levels. This had to be fixed before liquid breathing could be used in humans.
In 1966 Dr. Leland Clark and Dr. Golan experimented on liquid breathing in mice. Oxygen and carbon dioxide are very soluble in fluorocarbon liquids such as freon. Leland Clark realized that, if the alveoli of the lungs can draw oxygen out of the liquid and unload carbon dioxide into the liquid, these fluorocarbons should support respiration of animals. Testing first on anesthetized mice, he temporarily paralyzed each animal and put a tube down its trachea, inflating a cuff inside the airway to provide a seal and ensure that no air entered the lungs, and no solution leaked out. See the journal Science (24 June 1966). For a good history of early developments, read this paper (http://www.scienceweb.org/movies/wolf.htm).
After bubbling oxygen through the fluorocarbon, the oxygenated fluid was pumped into the animals' lungs, and recirculated at 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.
As in Kylstra's studies, Clark had problems due to the size of the animals' airways. The tiny size 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 and could not be removed fast enough. 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 prevented carbon dioxide buildup. The only way was to induce hypothermia in the animals. This technique seemed to give him the most success, as one animal survived over 20 hours breathing fluid at 18ºC.
All animals in the earliest studies suffered lung damage, but whether that was due to toxic impurities in the fluorocarbon, chemical interaction of the fluorocarbon with the lung, or some unknown effect, was undetermined. This mystery of the lung damage, and the problem of carbon dioxide elimination, and the body tissues tending to retain the fluorocarbon, would have to be solved before the process could be attempted on human subjects. Also, perfluorocarbon is denser and more viscous than air. This increases resistance and thus the effort needed to breathe.
Later developments
During later years, the techniques of fluid breathing were constantly refined and improved. The survival rate of all the tested animals in recent years has been very high, thanks mainly to improvements in carbon dioxide elimination. Current fluids used can dissolve over 65 mL of oxygen and 228 mL of carbon dioxide per 100 mL perfluorocarbon. By the early 1990's this procedure developed:-
- The animal was anesthetized with intravenous thiopental sodium. For more information on thiopental sodium, check out ScienceWeb Watches Television's article (http://www.scienceweb.org/tv/highincident.html) on the series "High Incident".
- The animal was put on its back. A tube was placed down its airway, ready for the liquid breathing medium.
- A blood sample was taken. The temperature of the fluid was adjusted correspondingly. It was no longer necessary to make the animals hypothermic.
- The perfluorocarbon was instilled into the animal's lungs through the tube.
- A floor-mounted 3-litre reservoir was filled with the perfluorocarbon. The liquid was driven by a pump through a series of machines which warmed and oxygenated the liquid and took the carbon dioxide out of it. The liquid flowed through a tube into a 3-way pneumatic valve which directed flow to the animal. A computer controlled the inspiration (18 mL of fluid per second), pumping the liquid into the animal's lungs, then back out again to the reservoir, at a rate of about 6 complete respirations per minute.
- At the end of the test, the animal was tilted for about 15 seconds and the perfluorocarbon was allowed to drain from the lungs. This can be seen in the film "The Abyss" where Ensign Monk drained the fluid out of the rat's lungs: in the filming, the rat genuinely breathed liquid.
These tests of the early '90s were successful: dogs could be kept alive in the perfluorcarbon medium for about 2 hours; after removal the dogs were usually slightly hypoxic, but returned to normal after a few days. When the animals were autopsied, the typical findings were mild edema and some hemorrhaging, clearly an improvement over the pulmonary damage of earlier tests. The procedure was ready for human subjects.
Use in diving
Breathing liquid instead of air seems odd, but if the technique could be perfected it would revolutionize diving.
In diving, the pressure inside the lungs must equal the pressure outside the body, to stop the lungs from collapsing. Thus, if the diver is f feet = m meters deep, and the air pressure at the water surface is p bars (usually 1, but less at high-altitude lakes such as Lake Titicaca), he must breathe air (or other breathing gas) at a pressure of f/33+p = m/10+p bars. This pressure quickly gets high with depth: around 13 bars at 400 feet, and around 500 bars on the oceans' abyssal plains. See this explanation (http://www.scienceweb.org/movies/abysslem.html) from scuba instructor Lem Bingley, and this response (http://www.scienceweb.org/movies/daveread.html) by diver Dave Read. These high pressures cause harmful effects on the body: see diving disorders and nitrogen narcosis and Decompression sickness, and this web page (http://www.scienceweb.org/movies/abysslem2.html) from Lem about decompression sickness and nitrogen narcosis. One solution is a rigid articulated diving suit, but these are bulky and clumsy.
With fluid in the lungs, the pressure in our body could match the pressure of the surrounding water without having to breathe so much gas. That would eliminate the need for decompression and its inherent problems, namely decompression sickness, nitrogen narcosis, and air emboli.
If the technique could be perfected, it would be extremely useful for submarine escape and undersea oxygen support facilities, and for underwater work, as portrayed in the 1989 science-fiction film The Abyss.
Medical uses
The immediate use of liquid breathing is likely to be in treating premature babies, and adults with severe lung damage from causes such as fires.
Liquid breathing began to be used by the medical community after the development by Alliance Pharmaceuticals of the fluorochemical perfluorooctyl bromide, or perflubron for short. Useful as a blood substitute and for liquid ventilation, perflubron (under Alliance Pharmaceutical's brand name LiquiVent) is instilled directly into the lungs of patients with acute respiratory failure (caused by infection, severe burns, inhalation of toxic substances, and premature birth), whose air sacs have collapsed. Once inside the lungs, perflubron enables collapsed alveoli (air sacs) to open and permits a more efficient transport of oxygen and carbon dioxide. Current tests are focussing on premature babies, but trials with adults are ongoing.
All blood that flows out from the heart to the rest of the body first must go through the lungs, where it picks up oxygen and gets rid of carbon dioxide. If the lungs do not function properly, as is common in premature infants with respiratory distress syndrome, the lungs become stiff and collapse, and the infants must be put on ventilators. A study, led by Dr. Corrinne Leach of the State University of New York at Buffalo, tested 13 infants on ventilators who were born prematurely with respiratory distress syndrome. The infants were at risk of dying because they could not produce a natural surfactant that stops the lungs from collapsing from surface tension. They were at risk of severe and permanent lung damage from the force of the ventilators that were inflating their lungs. Their lungs were filled with perflubron which would let the air sacs of the lungs open and permit breathing. The perflubron let the lungs inflate with less pressure and let oxygen pass through the lungs and into the blood stream and carbon dioxide out more efficiently and with less stress. This was successful.
The 13 premature infants received partial liquid ventilation for 24 to 76 hours; they were weaned back to gas ventilation without difficulties or adverse side effects, and 11 of the 13 showed significant improvement in lung functioning. Six of the infants eventually died, but of causes apparently unrelated to the liquid ventilation.
Clinical trials are with premature infants, children and adults are ongoing. Since the safety of the procedure and the effectiveness of the gas exchange have improved so much, the US Food and Drug Administration (FDA) has given the product "fast track" status (meaning a speeded-up review of the product, designed to get it to the public as quickly as is safely possible) due to its life-saving potential.
Possible other uses
Around 1970, liquid breathing found its way into fiction in alien spacesuits in the Gerry Anderson UFO series, to enable a spaceman to withstand extreme acceleration forces.
Acknowledgement
Taken, with permission from: Fluid Breathing (http://www.scienceweb.org/movies/abyss.html), and afterwards edited.
See also
External Links
- Alliance Pharmaceutical Corp (http://www.allp.com/)de:Liquid Ventilation