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Date: Mon, 28 Feb 2011 03:00:35 EST
Subject: Melody Maxim's Distorted Reality 21
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Sent: 11/21/2008 12:38:42 A.M. Pacific Standard Time
Subj: Re: [CI_Sci] mixing reservoir
NAME REDACTED, et al.,
There is no doubt that ramping up the CPA concentration for the first part
of CPA perfusion in the patient with little ischemic injury is ideal.
However, even in such good cases (now vanished from cryonics) it is arguably not
desirable to linearly ramp all the way up to terminal concentration; in
fact this is not what is done at 21CM, or Alcor, for that matter. We did it
in the early days because that's all we knew to do and even then we would
sharply increase the slope of the ramp if we encountered edema (always the
case in ischemically injured patients).
For the typical severely ischemically injured CI patient I would not
support ramping, but rather believe that stepped introduction with a doubling
of
concentration with each 'pass' is the best approach.
As to how to handle switching from one concentration to another or how to
'refill' a reservoir without introducing air, this is best done by using
TWO reservoirs which are set up as shown below:
This set-up allows you to switch from one concentration to another or to
refill a reservoir without introducing air. This set-up was rejected several
years ago as too complex. It completely avoids introducing air since you
fill reservoirs ONLY when you are not pumping from them.
You can also use a baffled reservoir like this:
The baffle (you can have more than one if needed) diffuses the stream of
liquid and channels or streams it down the sides of the vessel and this
avoids entraining air in the liquid.
This can also be done with a slotted or perforated tube anchored to the
side of the tank:
If you want to really equilibrate the patient with CPA and to introduce it
at a suitably non-toxic (low) temperature you will have to close the
circuit. This does not preclude fairly discrete steps up in concentration but
it
does blunt them a bit (which is probably good). Below is the protocol 21CM
was using to introduce and remove CPA from kidneys. It consists of a linear
ramp for the first part of the introduction procedure followed by a sharp
step up followed by a smaller (but still abrupt) step-up in concentration.
The step-ups are tolerable ONLY because the organ has first been loaded
with at least half the concentration to be subsequently stepped. Organs
tolerate gentle introduction of the first CPA much better than starting out
with
steps. In the case of M22 they've found that a linear ramp is necessary up
to ~5M CPA; they very much want to go faster to minimize exposure time, but
this was not a viable strategy.
Always remember that this is uninjured tissue under ideal conditions. The
problem with CI patients is that you are trading off reduced osmotic injury
for decreased cryoprotection (due to edema). Right now, that seems like a
very bad trade off.
This is what Alcor shoots for, and at least in this case, achieved
(courtesy of Brian Wowk):
Notice that it takes them 4+ hours to get to terminal (target)
concentration! This isn't being done because they want to be gentle it is what
is
actually required to achieve equilibration under real world conditions; the
steepness of the 'ramp' attests to this. Note that venous concentration take
quite awhile to equilibrate with the arterial concentration - over 2 hours in
fact. This may not be evident from the graph but what must be kept in mind
is that during the whole 'flat' part of the graph above 'concentrate' is
steadily being added to the system in order to maintain the desired 'target'
concentration in the recirculating reservoir (and thus in the patient).
This is very much my experience in ischemically injured patients and it is
why I do not believe that CI is reaching CNV in their patients. Too much of
the microvasculature is inaccessible to flow with the result being vastly
decreased surface area and much longer diffusion/equilibration times.
Mike Darwin
END OF COLD FILTER POST
Fance Department
(Login Finance_Department)
Veteran Member
Wow February 4 2009, 1:11 AM
What a lot of information! Thanks, Melody and Mike.
Carry on,
FD
Melody Maxim Melody Maxim
(Login melmax)
Filtered User
Been There, Done That... February 5 2009, 11:23 AM
...not inclined to do it again. I have no intention of even taking the
time to do anything more than glance at Mike's "Judge For Yourselves" posts,
much less to respond to them in detail. What Mike doesn't seem to realize is
that most of the audience here cannot "judge for (them)selves," which one
of us is making the better argument, in regard to perfusion equipment. I'll
just make a few brief comments:
1. Mike is unaware of a lot of my responses to his suggestions and
remarks. I'm not inclined to debate perfusion equipment and techniques at
length,
with Mike, because I find it to be mostly pointless and unproductive, and
thoroughly frustrating.
2. I can't bring myself to wade through a lot of Mike's written materials,
for a number of reasons. However, since he claims his review of SA was not
confidential, I wish he would post it somewhere. I knew very little about
what was going on in cryonics, when I read it, having just arrived on the
scene, so I can't really recall a lot of the details. As I've already
written, I was so put off by what I perceived as Mike's "hostility," (something
I
can now identify with), I could barely read the thing, and it was massive.
I'd be willing to give it a second chance, and possibly even review it, if
Mike would make it available to the public. (Unfortunately, I would guess
his copy doesn't include the comments and responses made by some of the SA
personnel that were included in the copy I saw.)
3. Pictures are not always "worth a thousand words." I could grab some
construction workers off the street, gown and glove them, sit them behind some
medical equipment and take pictures of them, and what would that prove?
Even the addition of a "legally dead" patient, or a dog, wouldn't make those
masked men and women competent. (As I recall, one of the photos Mike posted
on another discussion forum appeared to show a large bolus of air/foam in
the perfusion circuit, in the raceway of the pump. I didn't bother to
mention it.)
4. If Mike is, as Wikipedia indicates, "second only to Robert Ettinger as
one of the most influential figures in the controversial field of
cryonics," (http://en.wikipedia.org/wiki/Mike_Darwin), then he's been of
tremendous
influence in an endeavor that, in my opinion, is possibly one of the most
miserable failures in medical science history.
Mike Darwin Mike Darwin
(Login mgdarwin)
Veteran Member
Re: Been There, Done That... February 6 2009, 1:01 AM
Melody Maxim writes:
I have no intention of even taking the time to do anything more than
glance at Mike's "Judge For Yourselves" posts, much less to respond to them in
detail. What Mike doesn't seem to realize is that most of the audience here
cannot "judge for (them)selves," which one of us is making the better
argument, in regard to perfusion equipment.
Mike Darwin: So, if I understand Ms. Maxim's position correctly, the
intelligent laymen and the non-perfusionist professionals who populate this
list-serve are not capable of judging for themselves the merit of technical
alternatives in cryopatient care, such as the use of centrifugal versus roller
pumps, or open (hard-shell) versus closed venous reservoirs? Not even if
the relevant background is provided along with the opportunity to have any
questions answered? That's an amazing assertion and implies that the people
on this list-serve, as well as every other non-expert in the world, are
incapable of understanding and making decisions in situations where even more
complex scientific and technical issues are in play. So, by this rationale,
if you are not a board certified climatologist you cannot judge for
yourself whether global warming is real and come to a decision about what to do
about it? In my opinion, this is a condescending and patronizing statement
which also appears to be self-serving; only Ms. Maxim is qualified to decide?
Just because everyone will not (or cannot) understand a technical debate
does not mean that the debate should not be undertaken. While there are
certainly specialized venues for arcane scientific or technical discussions, the
issues in question here hardly qualify. If this is not the appropriate
place to discuss these and related issues, then where is the proper place?
Ms. Maxim goes on to write:
I'll just make a few brief comments:
1. Mike is unaware of a lot of my responses to his suggestions and
remarks. I'm not inclined to debate perfusion equipment and techniques at
length,
with Mike, because I find it to be mostly pointless and unproductive, and
thoroughly frustrating.
Mike Darwin: Well, if I am 'unaware' of a lot of Ms. Maxim's responses to
(sic) her suggestions and remarks that is easily remedied; why doesn't Ms.
Maxim post these responses and suggestions here? That seems only fair since
I can hardly be criticized for not responding to things I've 'never seen'
or 'am otherwise unaware of.'
MM: 2. I can't bring myself to wade through a lot of Mike's written
materials, for a number of reasons.
Mike Darwin: Well, at least share your reasons with us. Even more to the
point, can you cite these written materials which constitute such a vast sea
of wading?
MM: However, since he claims his review of SA was not confidential, I wish
he would post it somewhere. I knew very little about what was going on in
cryonics, when I read it, having just arrived on the scene, so I can't
really recall a lot of the details. As I've already written, I was so put off
by
what I perceived as Mike's "hostility," (something I can now identify
with), I could barely read the thing, and it was massive. I'd be willing to
give it a second chance, and possibly even review it, if Mike would make it
available to the public. (Unfortunately, I would guess his copy doesn't
include the comments and responses made by some of the SA personnel that were
included in the copy I saw.)
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