We scientists are difficult, cranky, and above all, maddeningly frustrating people. Want to turn lead into gold? No problem, we can tell you how to do that, and in fact have even done it already: the only catch is that the cost of such ‘nuclear transmutation’ is many times that of even the most expensive mined gold. You say you want to travel to the moon? Done! That will be ~$80 billion (in 2005 US dollars). Want to increase average life expectancy from ~45 to ~80 years? Your wish is our command, but be mindful, you will, on average, spend the last few of those years as a fleshpot in the sunroom garden of an extended care facility.
And so it has been with an effective treatment for cerebral ischemia-reperfusion injury following cardiac arrest. Thirty years ago, laboratory scientists found a way to ameliorate most (and in many cases all) of the damage that would result from ~15 minutes of cardiac arrest, and what’s more, it was simple! All that is required is that the brain be cooled just 3oC within 15 minutes of the restoration of circulation. The catch? Well, this is surprisingly difficult thing to do because the brain is connected to the body and requires its support in order to survive. And the body, as it turns out, represents an enormous heat sink from which it is very difficult to remove the necessary amount of heat in such short time. Thus, the solution exists and has been proven in the laboratory, but it has been impossible to implement clinically. This may be about to change as a variety of different cooling technologies, such as cold intravenous saline and external cooling of the head begin to be applied in concert with each other. Separately, they cannot achieve the required 3oC of cooling, but when added together they may allow for such cooling in a way that is both effective and practical to apply in the field. A newly developed modality that cools the brain via the nasal cavity may provide the technological edge required to achieve the -3oC philosopher’s stone of cerebroprotection.
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It is difficult to match concerns about reperfusion injury during cardiopulmonary resuscitation (CPR) with specific proposals for alternative interventions. After all, no matter how harmful the effects of oxygenation may be, not restoring circulation in a patient in cardiac arrest is hardly a credible option. One alternative would be to restore circulation but withhold oxygen (or ventilate with room air). Another alternative would be to induce hypothermia during circulatory arrest before restoring circulation.
A recent paper in Resuscitation investigated the latter option and reports that delaying reperfusion in mice until induction of mild hypothermia has been achieved can improve hemodynamics, survival and neurological outcome. The time to drop the temperature from 37 degrees Celsius to 30 degrees Celsius was 90 seconds in mice. As the authors note, “this is not currently feasible in humans and it is likely that much longer resuscitation delays in the clinical setting might counteract the benefit of cooling before ROSC (return of spontaneous circulation)”.
Rapid partial cooling (as the authors suggest) may solve this problem but restoring circulation will result in moving warm blood to the very organs (such as the heart and the brain) that just had been cooled. Such an intervention will only work if some of the protective mechanisms of hypothermia, such as altered gene expression, are (partially) retained during subsequent rewarming.
One treatment modality that the authors did not research, but warrants investigation, would be to “mimic” intra-arrest hypothermia by restoring circulation and giving a cocktail of neuroprotective agents prior to restoring oxygenation. Such an approach may not eliminate all free radical injury upon restoring circulation, or eliminate other elements of reperfusion injury such as calcium overload and inflammatory responses, but it might be an interesting treatment to compare with induction of intra-arrest hypothermia and delayed CPR.
After legal pronouncement of death, cryonics patients benefit from rapid stabilization to protect the brain from injury. The most fundamental intervention is induction of hypothermia. Unlike other interventions such as cardiopulmonary support (CPS) and administration of neuroprotective medications, induction of hypothermia is an intrinsic part of cryonics. Unfortunately, surface cooling with ice is not a very effective way to rapidly drop the core temperature of the patient. There are a number of alternative cooling methods such as peritoneal, colonic, and gastric lavage but these cooling methods can be logistically challenging and require specific (surgical) skills. As a consequence, application of these cooling methods in cryonics is rare. To date, rapid cooling in cryonics is achieved during blood washout, which requires surgical access to the circulatory system of the patient.
Because the neuroprotective effects of hypothermia on the brain are so profound it would be very desirable to be able to induce rapid cooling without the need for surgery and extracorporeal perfusion. In the mid-1990s, cryonics researcher Mike Darwin realized that one might be able to reap some of the benefits of cardiopulmonary bypass-induced cooling by using cold cyclic lung lavage with an inert liquid. Because all of the patient’s blood travels through the lungs, the lungs can be utilized as an endogenous heat exchanger to cool the patient. With his colleagues at 21st Century Medicine and Critical Care Research (CCR), a number of prototypes were built to deliver and remove chilled perfluorocarbons. Initial canine experiments using this technology were successful and in 2001 a paper was published that documented that cooling rates of 0.5 degrees C/min could be achieved. A number of different terms for this technology have been used including liquid ventilation, mixed-mode liquid ventilation (MMLV), and cold cyclic lung lavage, depending on which aspect of the technology needs emphasis, breathing or cooling.
A basic version of cold cyclic lung lavage with perfluorocarbons was used on Alcor patient A-1876 in 2002. This case constitutes the first documented case of cold cyclic lung lavage in cryonics. Although the case summary states that “the combination of external cooling in the ice bath and fluorocarbon cooling via the lungs had reduced her core temperature from around 36 degrees Celsius at the time of death to approximately 9 degrees in just two-and-a-half hours,” no specific details on the equipment or procedure are given. The report does indicate that rapid indication of hypothermia by delivering and removing cold perfluorocarbons from the lungs is technically feasible in cryonics patients. In 2007, the cryonics company Suspended Animation and CCR reported on the development and fabrication of advanced automated prototypes to induce liquid ventilation that can achieve cooling rates superior to the prior art. The recent prototypes are scaled for human lung volumes and could be used in a cryonics case if people are appropriately trained. Although the concept of liquid breathing is not new, the application of such technologies to induce rapid hypothermia to protect the brain is another example of how cryonics research can contribute to mainstream (emergency) medicine.