The Circle of Willes in Cryonics Perfusion

Blood flows into the brain primarily via the carotid arteries and the vertebral arteries. The Circle of Willis is a circular arterial structure in the brain that connects blood flowing in from the carotid arteries with blood flowing in from the basilar artery (which is fed by the vertebral arteries).
Blood flows from the Circle of Willis into brain tissue via the anterior, middle, and posterior cerebral arteries. Many studies have shown that the Circle of Willis is incomplete in most people. A 1998 study of 150 healthy adult volunteers showed a complete Circle of Willis in only 42% of cases — more often complete in younger persons and females [RADIOLOGY; Krabbe-Hartkamp,MJ; 207(1):103-111 (1998)]. A slightly more encouraging 2002 study of 118 healthy volunteers in the 65-68 age group, showed 47% had a complete Circle of Willis [THE JOURNAL OF CARDIOVASCULAR SURGERY; Macchi,C; 43(6):887-890 (2002)]

For cryonics purposes, it has been believed that perfusion into the carotid arteries, but not into the vertebral arteries will result in incomplete perfusion of the brain if the Circle of Willis is not complete. In particular, if both posterior communicating arteries are missing, then perfusing only through the carotid arteries will result in no blood getting to parts of the brain supplied by the posterior cerebral arteries. Both posterior communicating arteries were missing in 11% of those in the 1998 study and in 14% of those in the 2002 study cited above.

Nonetheless, a 2008 study showing Circle of Willis complete in only 40% of 99 patients found no case of insufficient perfusion in functional tests of patients given unilateral cerebral perfusion. The authors concluded that “extracranial collateral circulation” provides an alternative pathway to the Circle of Willis for cerebral crossperfusion [EUROPEAN JOURNAL OF CARDIOTHORACIC SURGERY; Urbanski,PP; 33(3):402-408 (2008)]. Although persons with missing posterior communicating arteries could easily have pathways to opposite sides of the brain, other variants of Circle of Willis incompleteness would be expected to prevent perfusion across hemispheres.

When the cryonics organization Alcor does a cephalic isolation (“neuro”) perfusion, the carotid arteries are initially cannulated and the vertebrals are not cannulated. Only if when the patient is being perfused into the carotid arteries no flow is seen coming from the vertebral arteries are the
vertebral arteries to be cannulated and the patient is to be perfused through both the carotids and the vertebrals. If, on the other hand, flow is seen coming from one of the vertebral arteries after perfusion of the carotids has begun, it is assumed that the Circle of Willis is complete and the vertebral arteries are clamped for the rest of the perfusion. Flow only needs to be seen in one of the vertebrals to confirm that the Circle of Willis is complete, because the vertebrals unite in the basilar artery before connecting to the Circle of Willis.

One Alcor employee has informed me that of 15-20 neuro patients perfused by this cephalic isolation method, not once has there been an absence of flow from the vertebrals and not once has Alcor perfused a cephalic isolation patient through the vertebral arteries. This would be slightly improbable, based on a 10-15% expected rate of incomplete communicating posterior arteries on both sides. But another Alcor employee remembers one or two cases where vertebral artery perfusion was done (which would match expectations).

When both posterior communicating arteries are not missing, there is another potential problem with perfusing only into the carotids and not the vertebrals — namely, loss of perfusion pressure. Perfusate entering the Circle of Willis could exit through the basilar artery (the vertebrals) instead
of through the cerebral arteries. Vascular resistance in the body is reportedly only one quarter what it is in the brain. Clamping the vertebral arteries (as is done during Alcor neuro perfusions) could prevent this problem. Blood flowing into the basilar artery need not be pushing all of the blood in the body, however, because arteries — and especially veins — have a large reserve capacity (a balloon-like ability to expand).

Possibly the reserve capacity of the brain would allow blood to flow into the brain as readily as into the body. Blood has about three times the viscosity of water, and vitrification solution has about twice the viscosity of blood. Viscosity will increase vascular resistance in all blood vessels, but the effect would be greater in the brain. The “no reflow” phenomenon would also create resistance in the blood vessels, which again might be greater in the brain than in the body.

Prior to the use of vitrification solution, the Cryonics Institute only perfused cryonics patients through the carotid arteries — there was no attempt to perfuse into the vertebral arteries. Nonetheless, dehydration was seen in the patients, and adequate effluent flow was seen from the jugular veins. Perfusion pressures were reportedly not excessive.

Currently, CI’s funeral director has been opening the chest (median sternotomy), and attempting to clamp the subclavian arteries, as well as the descending aorta, to perfuse into the ascending aorta. In several cases the ascending aorta has been perforated, forcing higher cannulations or the subclavians have been difficult to cannulate after having opened the chest. Our funeral director refused to open the chest at all for a known case of Methacillin- Resistant Staphylococcus Aureas (MRSA).

It would be preferable if a case could be made for perfusing all CI patients only through the carotids. Carotid-only has been recommended for vitrification perfusions overseas, as well as for glycerol perfusions in post-mortem sign-ups. Whether vitrification solution perfusion into the carotids can achieve adequate perfusion pressure in the brain — and whether adequate perfusion pressure can be verified by the observation of effluent from the jugular veins remains unresolved.

It should not be too difficult to clamp the vertebral arteries by cutting near the clavicle, as CI’s funeral director did when CI began the attempt to perfuse the vertebrals as well as the carotid arteries. Nonetheless, this would result in failure to perfuse portions of the brain supplied by the posterior cerebral arteries in the 10-15% of patients who are missing both posterior communicating arteries.

First published in The Immortalist, February, 2011 is the world’s largest independent website about cryonics and medical human biostasis.

In 2007 Aschwin de Wolf launched the cryonics blog Depressed Metabolism, the first professional blog to exclusively cover the science and practice of cryonics. Out of this platform emerged The Institute for Evidence-Based Cryonics (2008-2018), a non-profit aimed at educating the general public about cryonics. The Institute organized a number of groundbreaking symposiums on cryonics and dementia and cryonics revival scenarios. The Evidence-Based Cryonics Institute website also became the official host of the Scientist’s Open Letter on Cryonics and engaged in several campaigns to draw attention to recent breakthroughs in brain cryopreservation.

Biostasis continues the journey that started with Depressed Metabolism and the Institute for Evidence-Based Cryonics. Its goal remains to educate the general public about cryonics and human biostasis in all its aspects. We will keep publishing new content and historical documents relating to cryonics and remain the official host of the Scientist’s Open Letter on Cryonics. This year we will also announce the publication of the first detailed medical human biostasis protocol that will allow hospitals to educate themselves about offering cryonics as an elective medical procedure. In 2019 we will also announce a series of initiatives to study the theoretical aspects of conducting cell repairs at low-temperatures, or medical cryobotics.

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Scientific Optimism and Progress in Cryonics

“It is a strange matter of fact that those who watch and admire scientific research from the outside frequently have more confidence in its results than the men who cooperate in its progress” Hans Reichenbach – The Rise of Scientific Philosophy (1951)

The rationale for cryonics is that illnesses that cannot be cured by contemporary medical technologies might be cured in the future. But behind this rationale two different visions of scientific and technological progress compete for dominance. One perspective can be characterized as “medical conservatism.” History has shown that patients who were given up on in the past can be helped today. Although it is not known whether cryonics patients will be cured in the future, it would be prudent to preserve them in as pristine a condition as possible to allow for the possibility of resuscitation in the future.

The other perspective I want to characterize as “scientific meliorism,”[1] or the idea that scientific progress will continue at the same or accelerating pace, or even that anything that is not ruled out by the laws of physics will happen in the future. Although it is not always possible to draw an exact line between these two concepts, in this brief discussion I will address the limitations and dangers of scientific meliorism for the development of cryonics technologies and safety of our patients.

Scientific meliorism is not hard to recognize in arguments about aging and cryonics. People who share this perspective invariably argue that the developments that will conquer aging and resuscitate cryonics patients are not a matter of “if” but “when.” This perspective reveals itself when people are observed asking when aging will be conquered or when vitrification for whole body patients will become available. It is simply taken for granted that these developments are per definition possible and the only remaining challenges involve adequate fundraising and recruiting competent scientists.

In turn, scientists themselves can share this perspective when they present their work as contributions to the development of technologies that they know are possible. For example, when pressed for a timeline, such a scientist will estimate that a certain scientific breakthrough will happen before a specific date. To such a scientist, the question of whether such a milestone is possible at all is not given serious consideration.

In its worst incarnation, failure to meet these lofty goals is simply attributed to insufficient fundraising. Of course, if one believes that any scientific or technological challenge can be overcome given enough money one can always blame lack of progress on insufficient resources. But, as should be obvious, in that case claims about insufficient progress can always be blamed on lack of money and statements about estimated breakthroughs become non-falsifiable. A scientist can make himself immune to such attacks by outlining in advance how much money will be needed to achieve specific breakthroughs within a specific period of time. This will make the researcher (or fundraiser) more vulnerable to falsification, of course, but also more credible.

The scientific meliorist can employ two kinds of reasoning to support his case. The most popular is to frame the argument as a form of (naïve) induction. The reasoning here is that scientific and technological breakthroughs of the past will continue at the same or an accelerated pace, leading eventually to the development of strong AI, molecular nanotechnology, whole body vitrification, resuscitation of cryonics patients, etc. But as discussed by the 18th century Scottish philosopher David Hume about induction in general, this kind of argument cannot be supported by logic nor empirical observation. There is nothing necessary about these developments continuing in such a fashion and observation of contemporary developments do not force us to conclude anything about future developments. In short, claims about future scientific and technological progress cannot be supported by induction and require an element of psychological optimism that is beyond science.

A more abstract argument says that everything that is not ruled out by the laws of physics will eventually happen. For simplicity’s sake I will ignore non-technological events (such as wars and economic stagnation) that could interfere with such an inevitable  course of history in order to focus on the core argument itself. It seems to me that one flaw in this kind of reasoning is that it does not recognize the possibility that something that does not contradict the known laws of physics may not be possible within specific configurations of atoms that are required for life.

For example, although nothing in the laws of physics rules out the possibility of taking organic matter to cryogenic temperature and back without ice formation and without any adverse effects on viability, existing human physiology and biochemistry may not allow it for whole humans. Another example is human aging. Although we could conceive of complex configurations of molecules that do not age, or at least in which aging can be repeatedly reversed if it becomes detrimental, such a prospect may not necessarily apply to human biochemistry as it exists. Again we see that the kind of scientific and technological optimism implicit in this reasoning contains an element of psychological optimism that itself cannot be evaluated by scientific means. On the positive side, the examples used provide something of an “escape-route” because they permit the idea that human physiology itself can be changed through genetic engineering and artificial organ replacement to allow reversible human cryopreservation and effective treatment of aging even if existing human biochemistry does not allow it.

The sort of thinking that I characterized as scientific meliorism is not just an innocent form of extreme optimism about the future. When it comes to dominate our thinking about cryonics it can present a serious threat to the quality of care of cryonics patients because it tends to ignore or downplay the existing challenges of creating a physical infrastructure to support cryonics services and remain vigilant about its persistence. Although this relationship is not necessary, as a general rule, I have observed that people who possess this kind of abstract optimism (abstract because it is based on reasoning, not empirical observation) tend to have little interest in issues such as standby and stabilization, let alone the evaluation of existing cryonics case work. To these people, advances like brain vitrification are merely refinements and good public relations but not perceived as necessary to allow successful resuscitation of cryonics patients.

Scientific meliorism can also (subconsciously) sneak into the way we select and present evidence for the feasibility of cryonics. Instead of establishing what the consensus is on scientific and technical issues pertaining to cryonics, medical journals are being “mined” to find the most cryonics-supportive findings relating to cerebral ischemia and cryopreservation. Of course, in light of the tens of thousands of studies related to these topics it should not be hard to find outliers that justify the most optimistic interpretations about contemporary cryonics procedures. In the past this approach has been followed by Alcor when its promotion materials included incredible case reports from mainstream medicine about resuscitation after extended periods (an hour!) of normothermic cardiac arrest. In contrast, a more conservative and scientifically sound approach would be to defer to scientific and clinical consensus on these topics and determine how credible contemporary cryonics technologies and practices are in light of these findings. It should be stressed that when I speak about scientific consensus I am not suggesting that we should adopt the attitude towards cryonics that is often expressed by “experts” on this topic. In most cases these scientists are not experts on cryonics in any meaningful sense of the word and sometimes are even caught contradicting the scientific consensus in their own field in an effort to “debunk” cryonics.

The question we have to face is whether we want to present cryonics as a reasonable expression of medical conservatism that is supported by empirical results and reasonable expectations in cryobiology, resuscitation medicine, and molecular nanotechnology or as an expression of mainly abstract reasoning and futurism. The answer to this question is not academic but will have consequences for how we present cryonics, the alliances we attempt to establish, the procedures we adopt, and the importance we assign to ongoing cryonics research. Although advocates of cryonics still encounter a lot of irrational hostility from mainstream scientists and commentators, there are quite a number of opportunities for cryonics organizations to become serious contributors in debates about medicine, emerging technologies, and bioethics.

For example, a growing awareness is emerging in medicine that contemporary criteria for determination of death are becoming more and more controversial. The first major blow to our conception of death was dealt when advances in resuscitation medicine (e.g., CPR, defibrillation) restored life to people who in earlier days would have been given up as dead. A second empirical challenge to our conventional thinking about death was presented when artificial means enabled medicine to keep patients “alive” that are irreversibly brain dead. These developments led to the acceptance of two distinct criteria for determination of death: ‘irreversible’ cardiopulmonary arrest and brain death. But the co-existence of these two criteria should become a transient thing if we develop the means to preserve the viability of the brain, or at least prevent the neurological injury that normally precedes the diagnoses of brain death, through the use of low subzero temperatures.

Although the idea of information-theoretic death is useful, and a deeply ethical concept that justifies the decision not to give up too easily on a person that is considered dead by contemporary criteria, advocates of human cryopreservation do not need to embrace this alternative definition of death to make a persuasive case for its broader acceptance. Even the contemporary definition of brain death presents an opportunity to present empirical evidence that we may be able to avert the development of this fate in persons who cannot be salvaged by cardiopulmonary criteria.

This article started by contrasting medical conservatism with scientific meliorism and presented a critique of some of the assumptions that are implied in the latter perspective. In short, we may not realize how (dangerously) optimistic we are, especially as far as the practice of cryonics is concerned. But I want to conclude the article by pointing out that we may not realize how persuasive our position could be if we would simply stick to the cryobiological evidence that has been generated to date and its implications for contemporary debates on the definition of death. We should not expect that others will point to the implications of research that demonstrates that brain tissue can be reversibly vitrified with maintenance of electrical activity. There is an urgent need to make clear that cardiopulmonary death no longer requires us to accept that brain death will inevitably follow. We need to move beyond arguing about probabilities and the laws of physics and point out that even existing medical practice mandates a closer look at cryonics in light of its own criteria for determination of death.

So what do I recommend? I suggest that we recognize our (excessive) optimism about the future of science and technology and focus on what technical advances can be made right now to give cryonics a serious place at the table. If we support research to demonstrate that recovery of electrocerebral activity in vitrified whole brains is possible, and insist on its dissemination to science writers and the general public, we can start arguing that under ideal circumstances cryonics patients will meet the minimum medico-legal test of being alive. I further suggest that we re-direct some of our futurist interests to more tangible matters such as the legal, financial, and technical stability of cryonics organizations. We should be prepared to sacrifice some of our excessive optimism for a dose of healthy realism and anxiety. On the positive side, such a shift in focus will improve our chances of survival.

Recommended Reading:

Leslie Whetstine, Stephen Streat, Mike Darwin and David Crippen – Pro/con Ethics Debate: When is Dead Really Dead? Critical Care 9:538-542, 2005

Yuri Pichugin, Gregory M. Fahy, and Robert Morin – Cryopreservation of rat hippocampal slices by vitrification. Cryobiology 52: 228–240, 2006

Leslie Whetstine – An Examination of the Bio-Philosophical Literature on the Definition and Criteria of Death: When is Dead Dead and Why Some Donation After Cardiac Death Donors Are Not. Ph.D. Dissertation, Duquesne University, 2006

David Crippen and Leslie Whetstine: Ethics Review: Dark Angels – The Problem of Death in Intensive care. Critical Care, 11(1):202, 2007

[1] I owe the use of the phrase meliorism to characterize the kind of thinking about cryonics that is criticized in this article to Michael Darwin who had independently worked out a number of these themes in  his (unpublished) “Meliorism and Cryonics.”