Despite sensational news items about “zombie dogs,” biomedical researchers and clinicians have known for a long time that interruptions in consciousness and blood circulation can be reversed without neurological deficits, provided such events do not produce ischemic injury. There are even species who can enter a state of reversible metabolic arrest such as tardigrades (water bears). Naturally, researchers have recognized the opportunities that depressed metabolism holds for stabilizing trauma victims.  Although the jury is still out on the question if therapeutic hypometabolism can be induced in large animals by chemical means, there are no doubts that  lower temperatures reduce metabolism, allowing patients to tolerate longer periods of circulatory arrest.

The published record for reversible hypothermic circulatory arrest is 3 hours in a canine model. A recent study by Wu, Drabek, Tisherman et al. (2008) documented resuscitation from 3 hours of exsanguination cardiac arrest  (2.5 hours of no flow) after rapid induction of profound hypothermia using cardiopulmonary bypass. These results are quite impressive in light of the fact that in the latter study cardiac arrest was induced at normal body temperature by exsanguination, and the organ preservation solution to replace the blood consisted of just chilled saline plus dissolved oxygen and/or glucose. The authors attribute their success in extending satisfactory neurological recovery from 2 to 3 hours of exsanguination cardiac arrest to the addition of energy substrates, and oxygen in particular, during induction of profound hypothermia.

Research of this nature benefits cryonics in a number of ways. If hypothermic circulatory arrest will become routine in emergency medicine and military medicine, the general public will get increased exposure to the fact that circulatory arrest does not equal death. Research of this nature also demonstrates that induction of ultra-profound hypothermic arrest in humans may be reversible and therefore the initial stages of cryonics stabilization procedures as well. The more practical application is that it offers the prospect of extending the period the brain can be kept viable after pronouncement of legal death during remote transport of cryonics patients. Last but not least, this specific study provides optimism that viability of the brain can be maintained if hypothermia is induced after circulatory arrest, provided metabolic support is given and cooling rates are fast enough to avoid irreversible injury to the brain.

Unfortunately, the technical capability to reverse 3 hours of asanguineous hypothermic arrest falls short of what is needed for cryonics patients who are stabilized in remote locations. Transport times between the location of cardiac arrest and the cryonics facility often exceed 24 hours.  Although loss of viability of the brain does not constitute information-theoretic death, it would be desirable if cryonics organizations would be able to routinely secure viability of the brain between pronouncement of legal death and start of cryoprotectant perfusion.

Such advances will require substantial investments into  the development and implementation of improved organ preservation solutions, perfusion techniques, and resuscitation protocols. Potential directions  for such research include addition of effective neuroprotective compounds and “hibernation mimetics” to the organ preservation solution and low flow or intermittent perfusion during patient transport.

In 2005, when asked to comment on the prospects of using hypothermic circulatory arrest to treat trauma victims, Dr. Thomas Scalea, physician-in-chief at the R. Adams Cowley Shock Trauma Center at the University of Maryland Medical Center, was reported saying:

“As potentially crazy as this might sound, you’re comparing it against essentially certain death, so it’s hard to see how we can do any worse….all of us are incredibly energized by the thought of being able to do better.”

Such reasoning should equally apply to the practice of human cryopreservation, which employs even lower temperatures to protect people against “essentially certain death.”

27. July 2008 · Comments Off · Categories: Health, Neuroscience · Tags: , ,

More than a decade of basic research and clinical evidence now implicates inflammatory processes in the pathogenesis of Alzheimer’s disease (AD). TNF-alpha is a pro-inflammatory cytokine, also known as the “master regulator” of the immune response, and is the key initiator of immune-related inflammation in the brain. Much evidence has linked excess TNF-alpha to the development of AD, including the demonstration of 25-fold elevated levels of TNF-alpha in the cerebrospinal fluid of AD patients and the finding that beta-amyloid (the main constituent of the amyloid plaques found in the brains of AD patients) stimulates the secretion of TNF-alpha, which in turn induces beta-amyloid production in a vicious positive-feedback loop. This beta-amyloid-induced neuroimflammation has been shown to result in neurotoxicity and to upregulate other inflammatory mediators in the brain, including interleukin (IL)-1 beta, IL-6, and nitric oxide.

To examine the effect of downregulating this inflammatory process, a group of researchers performed a 6 month pilot study in 2006 to determine the effect of modulating TNF-alpha in AD patients using the specific anti-inflammatory agent entanercept (Enbrel). Enbrel selectively inhibits the biologic activity of TNF-alpha by binding to TNF-alpha and preventing its interaction with cell-surface TNF receptors.  Entanercept is already FDA approved for the treatment of such diseases as rheumatoid arthritis, psoriasis, and psoriatic arthritis.

Fifteen patients with mild to severe AD were evaluated before treatment began and once a month thereafter for six months using three standard measures of cognition: the AD Assessment Scale-Cognitive subscale (ADAS-Cog), the Severe Impairment Battery (SIB), and the Mini-Mental State Examination (MMSE). Treatment consisted of a total dose of 25 to 50 mg of Enbrel in sterile water per week via interspinous injection. This injection between two cervical vertebrae is hypothesized to improve flow of the drug to the central nervous system (CNS). All patients in this pilot study improved significantly on all assessments of cognitive ability, which is particularly amazing given the cognitive decline that would normally be expected of an AD patient over the course of six months.

As mentioned, this pilot study was approved to evaluate patients only at monthly intervals. However, during this six-month study and over the course of their clinical experience since the pilot study, the researchers noted “an unexpected and largely unprecedented clinical phenomenon… a noticeable clinical improvement within minutes of perispinal entanercept administration.” To validate these observations, the researchers performed a case study in 2008 in which a patient with severe AD was evaluated prior to, ten minutes after, two hours after, and one week after Enbrel administration.

Prior to treatment the patient had been unable to recall his birthday, his father’s occupation, or the names of any of the physicians treating him. He was not oriented to the calendar date, day of the week, year, place, city, or state. Ten minutes after receiving an injection of Enbrel, the patient correctly identified the state as California and his demeanor was observed to be calmer and more attentive. His responses to questions were less effortful, as well.

At the 2-hour post-evaluation, the patient was able to recall the name of his evaluator and was able to identify the month, day of the week, place, and name the state of California. He was slightly off on the calendar date and year, but “appeared more aware of his deficient performance.” The patient’s scores on all mental tests also improved dramatically. These improvements were maintained over the course of a week, whereupon he was evaluated again before receiving his next Enbrel dose. The patient continued to receive a weekly dose of Enbrel for a total of 5 weeks and was re-evaluated at 7 weeks (fourteen days after his last dose). His improvement in all areas of cognitive performance was marked and significant.

An important consideration when treating a patient with Enbrel, however, is that it is immunosupressive and as such leaves the patient at high risk of morbidity if they acquire an infection. This is especially important in late-stage Alzheimer’s patients, who are generally elderly, frequently visit hospitals/treatment centers, and live in community environments, making them particularly susceptible to community-acquired infection.

Following up on the publication of these unprecedented findings, the Life Extension Foundation recently published a review of both Enbrel pilot studies and the initial results of their own pilot study involving a 91-year-old female AD patient with severe cognitive deficits, who has also shown marked improvement in cognitive ability. The Life Extension Foundation is now eager to “launch an expanded study with the objective of measuring the long-term effects of weekly Enbrel injections plus nutrients that help suppress the production of excess TNF-alpha.” These trials are aimed at treating early-stage AD patients, and weekly Enbrel injections will be given in the Fort Lauderdale area.

To inquire about enrolling in this new study, contact the Life Extension Foundation.

26. July 2008 · Comments Off · Categories: Health, Science · Tags: , , ,

In a recent blog post, Overcoming Bias reports that Gary Taubes, who has written much to further the idea that refined carbohydrates are a stronger contributing factor to overweight and “diseases of civilization” than dietary fat and cholesterol, has compiled his thoughts on the subject in a major 600-page work called Good Calories, Bad Calories.

Why is Taubes so interested in bias?  For several decades, it has been the conventional wisdom that dietary fat (and especially saturated fat) contributes to obesity, heart disease, and cancer.  Judging from Taubes’ exhaustive research — indeed, I’d be surprised if any other book examined bias within a particular scientific field in such detail — the conventional wisdom was based on unreliable and slender evidence that, once established and institutionalized in government funding, set a pattern of confirmation bias by which further research was judged (or ignored).

Related: The Entitled to an Opinion blog on bad cholesterol and political correctness.

The two most popular technical arguments against human cryopreservation are that cryonics causes irreversible freezing damage and that the delay between pronouncement of legal death and the start of cryonics procedures causes irreversible injury to the brain. Such arguments can be countered by pointing out that freezing damage and prolonged periods of warm ischemia do not necessarily produce information-theoretic death. The argument that cryonics procedures themselves produce additional forms of injury which cannot be treated with contemporary technologies misses the point that cryonics involves stabilization of critically ill patients so that they can be treated with future technologies. In the case of freezing damage, this argument has also lost most of its value because today’s cryonics organizations employ vitrification agents to stabilize a patient at cryogenic temperatures without ice formation.

The criticism that delays between pronouncement of legal death and start of cryonics procedures will cause irreversible injury to the brain is also unfair because it treats the current social and legal obstacles to perform better stabilization of cryonics patients as an intrinsic element of cryonics itself. But cryonics does not necessarily involve cryopreservation of persons who have been pronounced legally dead. The current Wikipedia entry on cryonics defines cryonics as follows:

Cryonics is the low-temperature preservation of humans and other animals that can no longer be sustained by contemporary medicine until resuscitation may be possible in the future.

As can be deduced from this definition, cryonics constitutes a form of medical time travel that uses cryogenic temperatures to allow a terminally ill patient to reach a time when more advanced treatments may be available. As such, it would be premature to declare a cryonics patient “dead.” In most cases, pronouncing a person dead only reflects our current inability to treat the patient and our psychological need for definitive answers to questions of life and death. The limitation that cryonics procedures can only be started after pronouncement of legal death reflects the unfortunate fact that the current medical establishment does not recognize cryonics as a credible form of advanced critical care.

As a result, cryonics is currently practiced as a form of emergency medicine in which conventional resuscitation technologies such as chest compressions and ventilations are used to avoid the kinds of injury that follow after cardiac arrest. Although there will always be a place for cryonics as a form of emergency medicine to treat cases of trauma and  sudden circulatory arrest, most patients who currently present for human cryopreservation would benefit from more hospital cooperation in choosing cryonics as an elective medical procedure.

Although current cryonics organizations such as Alcor try to make the best of a bad situation by employing standby teams that allow rapid intervention after cardiac arrest to reduce brain injury, much improved quality of care of cryonics patients would be possible if cryonics procedures would start at a point where medical professionals (with informed consent of the patient and/or family) would determine that further treatment of the patient with contemporary technologies would be futile, or even counter-productive.

When this determination is made, conventional life support for the patient would be terminated and deep hypothermia would be induced using cardiopulmonary bypass. At deep hypothermic temperatures, the patient’s blood would be substituted with an organ preservation solution to reduce blood complications associated with lower temperatures. When the patient’s core temperature approaches the freezing point of water, the organ preservation solution would be replaced by a vitrification agent to allow an ice-free descent to cryogenic temperatures for long term care. After lowering the patient’s temperature below the glass transition point (Tg), the patient is maintained at intermediate temperatures to reduce the risk of thermal stress and fracturing that would occur at lower cryogenic temperatures.

If such hospital based human cryopreservation will be available, most of the injury that is currently incurred by cryonics patients can be eliminated. No longer do cryonics patients have to suffer harmful periods of shock, cerebral ischemia, and circulatory arrest before intervention is possible. Cryonics as emergency medicine will be confined to cases that constitute unexpected life-threatening events.

As this brief, but simplified, description of hospital based (or assisted) cryonics makes clear, ischemic brain injury is something that can be eliminated from cryonics procedures if the current restriction to limit cryonics procedures to clinically dead people were lifted. Such a change will not only improve the quality of cryonics procedures, it will also make cryonics available to cardiac arrest and stroke victims who can be resuscitated with contemporary technologies but will suffer delayed brain injury (often leading to higher-brain death) if they are allowed to resume life at normothermic temperatures.

Contemporary cryonics procedures do not need to cause “irreversible” brain injury or  massive freezing damage. There is good reason to believe that in ideal cases existing cryonics procedures can be successfully reversed up to the point of cryoprotective perfusion. The major limiting factor in cryonics is not “brain death” or freezing  but cryoprotectant toxicity. But even in this area cryonics associated research  companies are setting the standard for conventional cryobiology, as demonstrated by Alcor’s implementation of the vitrification agent M22 to cryopreserve its patients.

23. July 2008 · Comments Off · Categories: Cryonics · Tags: , ,

In January 2008, Alcor’s self perpetuating Board came under renewed scrutiny after long-time Alcor member and cryonics activist David Pizer tried to raise interest for changing the current system to a member elected Board. Alcor’s most publicly visible response to the arguments raised by Pizer was to publish a document by Board member Ralph Merkle defending Alcor’s self-perpetuating Board. What follows is a review of some of the arguments in that article.

The article asserts that a self perpetuating Board “is the most common way of electing Board members in non profit organizations.” As of writing, research by Charles Platt and Steve Bridge has not produced a definitive answer whether this statement is correct or not. But the real question is if the interests of Alcor are best served by a self perpetuating Board. Choosing an organizational structure for Alcor should not be a simple popularity contest because the nature of Alcor’s activities may warrant considerations that are not relevant to most non-profit organizations.

The article also states that “Alcor’s self perpetuating Board dates back to Alcor’s founding in 1972.” Research into this issue, however, established that this is not the case. The original Alcor bylaws gave some members the right to vote for Directors. The current understanding is that this system was changed as a result of the efforts of ex-Alcor President Mike Darwin, a change he now regrets as one of the biggest mistakes he made in cryonics. In his own words: “in structuring the Alcor Board election process as I did, I erred colossally, and really succeeded only in meeting one of the three criteria I had in mind: extreme stability.”

Some of the characteristics of many of Alcor’s past and current Board members include Alcor membership (required by the bylaws), a (long) history of Alcor involvement, and having served as an Advisor. These characteristics, or in the case of membership, a formal requirement, are not unique to self perpetuating Boards and can be required from candidates in member elected boards as well. This point raises a more general flaw in most arguments that have been put forward in favor of a self perpetuating Board; a lot of safeguards that are associated with self perpetuating Boards can be built into a member elected Board as well. As a matter of fact, one can imagine a member elected Board that has more safeguards than a self perpetuating Board. For example, Alcor’s current bylaws do not require anything other from potential Board members than Alcor membership.

A proponent of Alcor’s self perpetuating Board will need to present reasons why such a system has intrinsic elements that make it superior to a member elected Board. One such argument could be that Alcor’s first Board constituted the “elite” of Alcor members when it was formed and ensured that the Board will always consist of the elite of Alcor members. Proponents of a member elected Board may object that many of the characteristics that constitute an “elite Alcor member” tend to be objective in nature and can be formalized and written into the bylaws as conditions that need to be met for being a candidate for Board membership. The prospect of being subject to a general election will also provide an opportunity for members to investigate and evaluate such claims of excellence. It often happens that other members raise concerns and/or have information about potential candidates that Board members do not have access to. Although it is possible to encourage feedback from members (or Advisors) on potential candidates in a self perpetuating system, Alcor’s recent election of Board members indicates that the current Board is not interested in actively utilizing such a system.

One other potential defect in the current system of self perpetuating Board members is that it may not be well equipped to deal with situations where the Board has evolved into a Board that constitutes far from the elite of Alcor members. Advocates of a self perpetuating Board may claim that such a thing could never happen, but this seems to be overly optimistic. As a matter of fact, some current advocates of a member elected Board claim that we are currently in such a situation. Alcor has been criticized for promoting failed Presidents to the Board and electing Directors without even the most rudimentary understanding of readiness and cryonics procedures. Even if the probability of such a scenario happening is lower in a self perpetuating Board than in a member elected Board, the difficulty of reversing this situation in a self perpetuating Board presents a major challenge.

In other words, the question should not just be what system can be expected to generate the most competent board members, but also in which system incompetent or negligent Board members can be easily removed if such a scenario occurs. A member elected Board would not constitute a problem in this regard because members can vote (anonymously) to remove (or not re-elect) such Board members. In a self perpetuating Board, it is often painful for other Board members to propose the removal of another Board member. And if a Board has evolved in such a way that such Board members constitute all, or the majority, of the Board members it will be simply impossible.

Another argument that Merkle presents in his article is that Alcor Board members have access to all relevant information when they decide who should serve on the Board. There are a number of problems with this argument. The first problem is that it should be the goal of Alcor to make such information available to its members in the first place. Because Alcor is neither subject to market nor regulatory pressure, extensive dissemination of information to members is one of the few safeguards Alcor has to produce some degree of accountability. Granted, there can exist certain information that cannot be made available to the general membership (such as patient data), but this information is often of a nature that is not relevant in selecting a candidate. The second problem with this argument is that selecting a candidate for the Board is not only about “consuming” information, but also about making this information subject to a process of deliberation that produces informed decisions and, sometimes, novel perspectives. It is not obvious that a self perpetuating Board is the optimal environment for such deliberations. Finally, the argument itself may be flawed (or at least in the case of Alcor it may be). It is evident that existing Board members have access to information that general members do not have, but it is not evident that the information the Board has is more relevant than the information the total membership has or can generate.

One argument that is often raised is that Alcor’s primary mission is to maintain the current patients in biostasis and that these patients cannot benefit from giving members the right to vote for the Board. But it is not clear why this situation mandates a self perpetuating Board. This is something that needs to be argued for, and cannot be assumed. Current patients might be expected to be safer under a self perpetuating Board but the stakes are also higher because a failing Board cannot be removed by the members. One may also reason that maintaining the current patients in biostasis requires a conservative Board that is not subject to short-term politics. As a matter of fact, it is sometimes claimed that the Alcor board cannot be too aggressive in holding management accountable because the resulting tensions may destabilize the organization. Some critics point out that this argument holds existing patients hostage to future patients. Such a scenario might be avoided if Alcor’s daily operations (readiness, research, etc.) are completely separated from long term patient care. Instead of enforcing conservatism upon every aspect of the organization for the sake of stability, the part of Alcor that warrants extreme conservatism can be made completely independent from Alcor’s daily operations.

Merkle writes that “discussions with both new members and members who decide to leave Alcor do not support the idea that the presence or absence of a member elected Board directly influenced their decision.” The most surprising aspect about this statement is that these kinds of data exist at all and have not been communicated to Alcor members in a systematic fashion. But is it persuasive? If many Alcor members are leaving (currently one member is leaving for every two members who join) this may reflect dissatisfaction with aspects of the organization that are under the control of the Alcor Board. At the very least, this situation seems to be an indictment of the current Board.

Merkle also points out that during the recent Alcor conference only a minority of the audience preferred a member elected Board. What he does not mention is the fact that the people who raised their hand in favor of a member elected Board included a fair number of Alcor insiders who are quite knowledgeable about Alcor’s operations, including the person who changed Alcor to a complete self perpetuating Board, Mike Darwin himself. One also wonders what the result would have been if Merkle would have asked the conference attendees to raise their hand if they are in favor of increased membership participation and better accountability at Alcor. Clearly, there is a “framing” issue at play here. Another issue to consider is that the public nature of requiring a “show of hands” response to such a question may cause people not to vote against the status quo (as represented by Merkle himself), so as not to appear disagreeable or be labeled as a dissenter. Merkle’s argument would have been a lot more persuasive if opponents and proponents of a member elected Board would have presented their arguments on stage, followed by anonymous voting.

In conclusion, some advantages that are associated with self perpetuating Boards can be built into a member elected Board as well, some intrinsic advantages of self perpetuating Boards are uncertain or may become serious disadvantages in some scenarios, and other advantages are just assumed and not argued for. But there seems to be one thing that both sides agree on: if there is going to be any change, it can only come about if advocates of stronger membership involvement present detailed proposals to replace the current system and present evidence that Alcor has survived but only as a shade of its former self.

First published on Reform Alcor (February 2008)

22. July 2008 · Comments Off · Categories: Cryonics · Tags: ,

The following announcement from the Alcor Life Extension Foundation is indicative of its renewed focus on professionalizing the organization and improving the quality of readiness and patient care:

On June 7th and 8th, 2008, the Alcor board and management held a 2-day strategic planning meeting at the Alcor facility in Scottsdale, Arizona. At that meeting a funding offer brought forward by board member Saul Kent was accepted by the Alcor Board after considerable discussion.

The funding offer was made by three donors: the Life Extension Foundation, the Miller family, and Edward and Vivian Thorp, who will each contribute $150,000 a year to Alcor for three years, totaling $1,350,000. The funding provides for searches and three years of salary support for a CEO and a Transport Coordinator, who will be responsible for the early stages of the cryopreservation of Alcor patients. The funding will also pay to improve readiness for cases at Alcor and provide a 10% raise in salary for three years for the entire Alcor staff.

The position announcements for the CEO and Transport Coordinator positions are shown below. Information about how to apply for these positions is included. Those who wish to apply can do so immediately.

Complete post on the Alcor News Blog.

An important objective during stabilization of cryonics patients is restoring circulation of blood to the brain. In ideal cases, this can be achieved by aggressive mechanical cardiopulmonary support, hemodilution ,and administration of vasoactive medications. In not-so-ideal cases, one or more of these interventions are omitted or delayed. This raises the question if low flow perfusion scenarios can be detrimental to the brain because of increased reperfusion injury.  In a previous post, a paper was reviewed that found that (very) low cerebral blood flow was better than no flow at all, allowing a wider therapeutic window for successful resuscitation. Why do the low flows generated during manual cardiopulmonary resuscitation (or cardiopulmonary support in cryonics) improve the likelihood of successful neurological recovery?

In a recent paper (2008) in Resuscitation, Rea, Cook and Hallstrom propose that the low flow state generated by manual CPR simultaneously protects against ischemic injury and limits reperfusion injury. They speculate that low flow during CPR “arrests” ischemia and induces post-ischemic conditioning, which reduces exposure to peak values of oxidative stress and increases resistance to reperfusion injury when normal flow is restored:

If full flow was restored early on after collapse, the accumulation of stress mediators would be relatively modest and so the cell could tolerate reperfusion injury without moderating the peak level of oxidative substrate or priming the cell’s protective pathways. However as the duration of no flow increases, stress mediators accumulate to a level where full or near-full flow would produce oxidative injury that would overwhelm the cell unless peak oxidative stress levels are mitigated and protective pathways are preemptively up-regulated, as might occur with graded flow.

The authors even speculate that in some scenarios manual CPR might be superior to newer devices and techniques (such as  automated vest CPR or active compression-decompression CPR) that can restore blood to physiological levels because manual closed chest CPR protects the heart and brain from peak levels of stress mediators.

As the authors note, if this hypothesis is correct, treatment of cardiac arrest would require a highly individualized approach “whereby certain physiologic states would be best served by different levels of circulation and hence distinct doses of CPR.” Such treatment modalities will require complicated monitoring and resuscitation efforts, such as automated control over perfusion pressure and ventilation during CPR.

Although this model makes sense from a theoretical level, it seems to be at odds with the discovery that low flow perfusion cannot reverse the “no-reflow” phenomenon. If blood flow cannot be restored to some parts of the brain, it is not likely that ischemic injury can be “arrested” in those areas. It also seems to be at odds with the work of other resuscitation researchers who found that increased perfusion pressures and hemodilution can increase the time that resuscitation from normothermic ischemia is possible. And because low flow perfusion limits the rate of external and internal cooling, such graded resuscitation strategies decrease cooling rates if resuscitation is complemented with induction of hypothermia. Perhaps the authors could also improve on their own model by allowing aggressive reperfusion but without oxygen (or just room air) during the early stages of reperfusion.

Because rapid induction of hypothermia is the most fundamental intervention in human cryonics preservation, the relevance of this model may be limited. However, in cryonics stabilization circulation is usually restored before any significant temperature decreases are possible.  Cryonics patients often have distinctly different pathophysiological characteristics, which makes straightforward application of such models, if practical at all, extremely challenging. As has been reiterated before, without the creation of realistic cryonics research models and serious efforts at monitoring cryonics patients during transport, it will be hard to evaluate the relevance of recent insights in resuscitation medicine and extrapolate its findings.

20. July 2008 · Comments Off · Categories: Cryonics, Death · Tags: , , ,

Let’s face it: we’re all (still) getting older, and aging leads to death. This is a major reason for cryonics’ existence — to preserve ourselves, usually in an aged, diseased, and/or deteriorated state, until medical science is capable of curing our ailments and prolonging our lives. Because many people (especially young cryonics supporters) tend to think that they will benefit from radical life extension therapies in their own lifetime, some choose to forgo making early cryonics arrangements. As discussed in a recent post, even if aging is ended or reversed there will remain a non-trivial risk of death by accident or other fatal incidents. Others who support cryonics but endlessly put off making their own arrangements also take an enormous risk in securing their own cryopreservations. It is important to be an activist for your own cause, too, after all.

That most people do acquire the financial means and/or appropriate insurance coverage to make arrangements as soon as they determine that they want to be cryopreserved is a cornerstone upon which cryonics providers rely to operate as efficiently as possible. The fact is that life insurance is easiest and cheapest to obtain when you are young and healthy. In an age where people nonchalantly dole out hundreds of dollars a month for their cell phone usage, life insurance coverage that will pay out the required amounts for your cryopreservation upon legal death is a trivial payment (on the order of $20-80/mo for a healthy young adult). Even if you are not totally sure yet whether you want to be cryopreserved, obtaining insurance at a young age that can provide for your cryopreservation is a wise move. Arriving on the doorstep of a cryonics provider as a “last minute case” is not advisable, since these are often the most demanding and controversial cases, and are also frequently subject to family interference.

Unfortunately, there are situations in which persons who have been dedicated to cryonics for many years fall upon hard times or are otherwise disposed of the ability to maintain their cryonics arrangements. For these legitimate cases, a plea for help can be raised when presented with adequate information concerning the person, their involvement in cryonics, and the nature of the circumstances leading to their disability to provide funding for cryopreservation. Of course, those who are already disabled or terminally ill before hearing about cryonics make up a good proportion of these legitimate claims, as well.

However, some of these “pleas for help” are not infrequently issued to the general cryonics populace at large via cryonics-specific Internet message forums, with little to no circumstantial information provided to assess the validity of the request. Such requests leave a lot to be desired in terms of properly addressing the need of the person desiring assistance, and devalue the importance of acquiring and maintaining cryonics arrangements throughout life, so they are not dependent upon others when bad times finally do befall them.

Looking forward, the last thing cryonics providers need are multiple series of last-minute cases and daily fundraising appeals when the “Singularity” turned out not to be as near as some people might have thought….

18. July 2008 · Comments Off · Categories: Cryonics · Tags: , , ,

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.

One concern about prolonged cardiopulmonary support in cryonics is that its decreasing effectiveness may not be able to meet cerebral oxygen demand, and may even become detrimental. Some investigators have  observed that severely reduced flow (cerebral blood flow less than 10% of control) to the brain may actually be more harmful than no flow at all.  Explanations of why incomplete (“trickle flow”) ischemia may be worse than complete ischemia include aggregation of slow moving blood cells,  glucose-induced excessive lactate production, and oxygen-induced free radical damage to membranes.

In contrast, a study by Steen et al. concluded that some blood flow is better than no flow at all. The authors found that dogs could sustain only 8 to 9 minutes of complete ischemia but 10 to 12 minutes of incomplete ischemia (cerebral blood flow less than 10% of control) without neurological impairment. These results are at odds with the findings of Hossmann et al. who found better electrophysiological recovery in cats and monkeys after complete ischemia, and studies by Nordstrom et al. who observed increased metabolic recovery in rats after complete ischemia.

The authors speculate that these differences may reflect the different durations of (in)complete ischemia. Hossmann et al. studied 60 minutes of ischemia and Nordstrom studied 30 minutes of ischemia. The authors note that the durations they studied (8-14 minutes) are more clinically relevant because neurological recovery with contemporary technologies is not possible after 30 or 60 minutes of cerebral ischemia. Although these findings provide support for restoration of any kind of cerebral circulation after cardiac arrest, it does not offer much guidance in evaluating the practice of prolonged cardiopulmonary support in cryonics.

The authors also draw awareness to the difficulty of correlating electrophysiological and metabolic recovery to neurological recovery. They quote a study by Salford et al. who observed some return of metabolism even though histological abnormalities had already been developed. Such studies warrant caution about using return of electrophysiological activity as an indicator of cerebral viability because it is not likely that such viability can be sustained over the long term, let alone predict functional recovery of the brain.  It is doubtful that viability in the latter, stricter, sense can be maintained during stabilization of most, if any, cryonics patients. At best, the studies that demonstrate recovery of electrophysiological and metabolic activity after prolonged cerebral ischemia offer hope that such periods of circulatory arrest do not produce acute information-theoretic death.

No metabolic or histological evidence was found to support the implication of no-reflow, lactate accumulation, and free radical damage in incomplete ischemia.  Again, the authors speculate that no-reflow may be more pronounced during longer periods of incomplete ischemia, an observation that seems to be indirectly supported by Fisher et al. who observed progressive impairment of perfusion for longer periods of ischemia.

Cryonics patients often experience shock, blood coagulation abnormalities, and decreased cerebral perfusion prior to pronouncement of legal death and cardiopulmonary support.  An additional complicating factor in cryonics is that cardiopulmonary support is often supplemented by induction of hypothermia and administration of vasopressors and neuroprotective agents. Although the paper by Steen et al. addresses a lot of issues that are important to evaluate cryonics procedures, it is clear that for real empirical guidance regarding the wisdom of prolonged cardiopulmonary support specific cryonics research models are required.