X-Message-Number: 1168 Subject: CRYONICS Gas/Liquid phase cooling From: (Edgar W. Swank) Date: Mon, 24 Aug 92 19:05:04 PDT OK for sci.cryonics OK for Cryonics Digest In response to my posting about gas phase freeze/thaw technique, designed to keep an open circulatory system at all times (Msg # 1112), Rich Schroeppel has sent me several E-mail messages directly commenting and offering suggestions. With his permission, I'll now share a summary of our exchanges with you. Rich (Aug 7): There are a fair number of fluids that remain liquid well below the temperature of freezing water. Your heat-transfer fluid doesn't have to stay liquid all the way down to LN2, just far enough that the cells are shut down. Edgar (Aug 14): No, the main benefit of using a gas coolant was to have the circulatory system free for the benefit of whoever attempts a revival. A coolant liquid at LN2 might be OK, but not a solid. Another benefit of fluid down to LN2 would be more uniform cooling/rewarming which might reduce some of the thermal stresses which now cause gross cracks to appear. Rich (Aug 7): Ordinary alcohol is liquid down to some surprising temperature, I think well below dry ice. It's probably out for chemical reasons, though. Freons would be an obvious candidate for the early cooling; maybe CF4 or CH2F2. For the later cooling, Xe or Kr, or maybe Ar; I'm not sure what the liquid ranges of these are, but they can be increased through modest high pressure. N2 might be the last coolant, although boiling could be a problem. Edgar (Aug 14): >From an old Handbook of C & Ph. B.P. M.P. Deg C N2 -195.8 -209.86 Kr -152.9 -156.6 Xe -107.1 -112 Ar -185.7 -189.2 So you can see all the noble gases don't have sufficient liquid range. My old handbook didn't have any info on Freon or other CF's, but I like your idea for early cooling. This might be a good candidate for a transition fluid from liquid to gas. The problem is, each liquid used in the procedure must mix fairly well with the liquid which proceeds it so that it can flush it out. I think I remember hearing that Freon is pretty non-toxic. On the other hand, alcohol mixes very well with water as well as reducing the freezing point. But alcohol is pretty toxic, but maybe not too much below 0 deg C? Rich (Aug 17): I spent a few minutes last night poking through my Handbook of Chemistry & Physics, and the Merck Manual. Some candidate fluids, with wide liquid ranges, are NF3, C2H6, CF4, CF2Cl2, C3H8, and CHFClBr. They are generally described as "inert", not much solubility in water, not explosive, fairly wide liquid ranges. Typical toxicity is "simple asphyxiant", which I take to mean "safe" in our context. I have two reservations with gasses as coolants: the first is that the heat capacity is small, on a volume basis, so lots of gas is needed to transfer a little bit of heat. The second is hard to quantify, but my feeling is that the fluid should have roughly the same viscosity as blood: if it's too much greater, it can't get through the capillaries (without a damaging head of pressure further back in the arteries); if it's too much less, I'd expect it to find some pathway through the system and ignore the rest of it. I'm assuming that liquids are better for these reasons. There are a lot of liquids available, so if the ones I've suggested don't work out, there are alternatives. Propane (C3H8) is somewhat magic, in that its boiling point varies a lot with pressure; if we can pressurize the patient to ~30 atm, then it's liquid at 37C. There are flammability problems though. Also, any air spaces in the patient would be crushed; the ones that come to mind are the middle ear, the sinuses if blocked, and the GI tract. The lungs could also be a problem. The choice is a bit cramped at the LN2 temperature range, although I suppose LN2 itself is a candidate. There's a lot of nuisance with using multiple cooling fluids, etc. to work out; but simply freezing a rat & reviving it would be a big step forward; the descent to LN2 temperatures could be a second experiment. One of the freons would be the ideal liquid for the simple freezing experiment. Maybe CF2Cl2. Edgar (Aug 20): Re the fluids you mention, all the characteristics sound good EXCEPT "not much solubility in water". We need a transition liquid miscible in both water and NF3, etc. Do your handbooks offer any possibilities? Alcohol still looks good except for toxicity which may not be a problem below 0 C. Do NF3... mix well with alcohol? Rich (Aug 20): I think "not soluble in water" is *good*. It means that the fluid acts solely as a heat transfer agent, and not chemically. This should be helpful in preventing toxicity. It also means that the fluid won't diffuse into the patient, so we can get it all back out. Propane worries me a bit in this respect; the recovering patient might retain quite a bit of propane. If it acts solely as a dissolved-gas anesthetic, then the patient should recover as it gradually diffuses out. I think alcohol is bad: It will be chemically active well below 0C, and it will lower the freezing point of any water it mixes with. It will probably diffuse into the patients cells and screw them up badly. Edgar (Aug 23): While I agree that non-soluble in water also tends to mean inert and non-toxic, there is still the problem of washing out the water-based blood or currently used cryo-protective blood substitutes. I'm afraid that trying to wash out a water-based liquid with something else that won't mix with water will get the same result as trying to wash out a liquid with a gas. "Bubbles" of one liquid within the other and an incomplete removal of the water-based liquid, leading to solidification and clogging of the circulatory system at lower temps. By the time alcohol is introduced, temperature should be far enough below zero C that cell interiors are frozen solid. Hopefully that should limit diffusion of alcohol into the cells. We still may have to worry about alcohol attacking or dissolving the cell walls it contacts. Both of these concerns are easily tested experimentally. Make a (simplified) glass model of the circulatory system including many capillary-sized glass tubes in parallel. Fill the system with water. Try to wash out the system by pouring in Freon, etc. See how many of the capillaries still contain water. Try the same thing on a hamster; once pure Freon is the effluent, dissect & see how much water was left. Take various tissue samples at (say) -5 deg C. Immerse in alcohol pre-cooled to -5 C. Remove, wash, and examine microscopically for damage. Or try live cultures that survive a round trip from -5 C and see how many stay alive after immersion in alcohol, washing & re-warming. Edgar (Aug 20): I don't think low heat transfer of gas is a concern. Current practice is to cool patients from dry ice temperature (with ice clogged circulatory system) to LN2 by dangling them *in vapor phase* above boiling LN2. Rich (Aug 20): I'll concede this point. I'll note that handling liquids is somewhat easier than handling gasses, but that the difference in convenience would be outranked by any substantial benefit to the patient. Edgar (Aug 20): I agree that viscosity much higher than blood (or containing particulates much larger than blood cells) is a concern, but I don't see the concern for less viscosity. Helium, especially, is likely to find new pathways even finer than the capillaries, but I don't see the harm. A large leak or "short circuit" in the circulatory system will be a problem with high or low viscosity. A small leak should still allow some pressure differential across the capillaries. However, it's been a long time since I had basic fluid dynamics in College, much less anything advanced. Rich (Aug 20): I'm only going on gut feeling here; I've never had any fluid dynamics training. My worry is that the He (or other low viscosity fluid) will find a few easy paths through the circulation, and ignore the rest. The patient will remain mostly full of blood, defeating your goal. Live people must have some active system controlling vascular resistance locally, to let the right amount of blood through. Edgar (Aug 20): Re using propane & 30 atm. I don't think it would be a big problem to catheterize the air spaces you mention in advance of starting perfusion. The main danger seems to be to the perfusion team (and patient!) from fire and explosion. Certainly the patient needs to be completely enclosed and all oxygen flushed out before introducing propane. We have to flush out the propane (with helium?) before LN2 anyway so this is not an ongoing hazard. Rich (Aug 20): Well, people do successfully handle propane every day, so it must be a solved problem. A few percent oxygen is okay, as long as it's below the explosion threshold. A "no ignition sources" rule might be a real nuisance, implying sealed motors, all metal objects grounded, who knows what. We need information from someone with handling experience. Rich (Aug 19): I did a bit more bookwork, with the Merck Manual. LN2 boils at 77K = -196C. NF3: melts -208.5, boils -129. (All Centigrade, of course.) Insoluble in water, rather inert chemically. Toxicity: Prolonged exposure may cause mottling of teeth, skeletal changes; see Chronic Effects of NaF. [I'm proposing short term, intimate, acute exposure at low temperatures. I'll hope that it's harmless. Their data is presumably for the gas.] CCl2F2 (Freon12) melts -158, boils -30. At 10 atm pressure, boils 42. Insoluble in water. Toxicity: Zip. C5H12 (normal pentane) melts -130, boils 36. Slightly soluble in water. Flammable. Toxicity: Narcotic at high concentrations. [I assume this is due to the solubility, and maybe to lack of O2. I hope that short term exposure to the liquid is harmless.] It looks like pentane & NF3 are a plausible pair of cooling fluids. Freon12 could be a bridge if the overlap between -129 & -130 is uncomfortable; or a mixture of pentane + Freon12 should have a slightly lower melting point, without lowering the boiling point too much. Pentane is imperfect. The Merck doesn't have all the different possible combinations of alkyl halogen compounds; there may be a freon that has a suitable liquid range, is not water soluble, and not flammable. I'd want to examine fully substituted propanes, maybe half F & half Cl; say C3Cl4F4. Edgar (Aug 21): It certainly looks like you have found a good set of fluids that together encompass a liquid range from above zero C to below LN2. It seems we have an option to store at LN2 with either gaseous Helium or liquid NF3 (which may also prevent tooth decay! (:) ). As I said in my previous msg, the problem is lack of a transition fluid that IS soluble both in water and the organic fluids you suggest. I can't think of anything better than alcohol offhand. -- (Edgar W. Swank) SPECTROX SYSTEMS +1.408.252.1005 Silicon Valley, Ca Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=1168