X-Message-Number: 33368
From: 
Date: Mon, 28 Feb 2011 01:19:23 EST
Subject: Melody Maxim's Distorted Reality 3

Content-Language: en

 
Melody Maxim writes:   
When the flow  transducer would not work with CI's solutions, I attempted 
to persuade Ben to  allow me to find another way to measure the flow. There 
are other ways, and I  felt the safety of the centrifugal pump, (it makes it 
virtually impossible to  pump air to the patient), far out-weighed the 

inconvenience of finding an  alternative for measuring flow. I did not try very
hard to convince Ben, because  I sensed he was uncomfortable with the pump, 
and I felt certain there was no way  for me to make him comfortable with it, 
in the three short days I would be  there. He seemed quite happy with the 
occlusive (roller) pump I had helped him  acquire, so I volunteered to 
purchase the centrifugal pump back from CI. I told  Ben I wanted to do some 

experiments with the pump, and I did, but the main  reason I wanted to buy the 
pump 
back from CI was that I did not want them to be  out $1,800 for a pump they 
purchased on my advice, but would not be using. I  even paid for them to 
ship it to me.  
Mike Darwin: This a  good example of something learned over two decades ago 
by professional  cryonicists through experience. Had Ms. Maxim established 
a dialogue with me  this information would have undoubtedly been quickly 
passed along. Flowm eters  on earlier clinical centrifugal blood pumps do not 
work on either asanguineous  solutions or on low ion content solutions 

(including washout solutions such as  MHP and mRPS-2 used by CI) because they 
are 
electromagnetic (EM) flow meters. EM  flow meters work by measuring the 

distortion in the magnetic field created as  ion containing fluid moves through
that field. There are two sources of ions in  blood: the dissolved salts of 
metals such as sodium, potassium, magnesium, etc.,  and the iron present in 
the oxygen carrying protein hemoglobin. It is possible  to recalibrate EM 
flow meters for asanguineous solutions that have ion levels  reasonably close 
to that of blood, but these flow meters do not perform  accurately or at all 
in some cases, if the ion concentration in the solution is  much lower than 
that of blood (or other body fluids).   
TBW solutions are  designed to inhibit the cell swelling that normally 
occurs in ultraprofound  hypothermia due to inactivation of the cellular ion 

pumps that normally control  cell volume (and ion content). This is done by the
expedient of replacing most  of the ions that are permeable to the cell 
membrane with other, larger molecules  that cannot enter the cells. Typically, 
what has been used as impermeant species  to replace the ionized species 
normally present in blood are sugars (glucose,  lactobionate, raffinose), a 

sugar-alcohol (mannitol) or (in the very early days  of organ preservation) the
phosphate salts of sodium and potassium (e.g.,  Collins' Solution).  
Even  non-perfusionist cryonics personnel, such as Fred Chamberlain, wanted 
to use  centrifugal pumps, and indeed, as I previously pointed out here, 
the first  purpose-built cryonics perfusion equipment was executed using 

centrifugal  pumping technology. However, the problem of flow measurement had no
ready  solution even though many things were tried. To name a few: in-line 
paddle wheel  flowmeters, differential pressure manometer flowmeters and 
falling ball  flowmeters. Sure, it was possible to get accurate flows with all 
of these  techniques, but only for perfusates of a fixed viscosity which 
meant that both  the composition and the temperature had to remain constant.   
Clearly, this is a  problem in cryoprotective perfusion where increasing 
concentrations of  increasingly viscous CPA(s) result in dynamically changing 
perfusate viscosity.  However, it was also a problem in recirculating CPB of 
cryopatients prior to  cryoprotective perfusion. This was so because the 
character of the recirculated  perfusate changed radically as its ion content 
changed (equilibration with the  large store of ions in the patients 

tissues) and as its water content changed  due to movement of water (usually 
edema 
fluid) from the interstitial space of  the patient into the vascular 
compartment where comparatively hyperoncotic and  hyperosmotic perfusate was 
circulating.  
Recent generations  of centrifugal CPB equipment use ultrasonic Doppler 
flow meters. These flow  meters work using a phenomenon first discovered by 
Christian Doppler in the  1840s. He noticed that a stationary observer 

perceives a sound to have shorter  and shorter wavelengths as its source 
approaches; 
and longer wavelengths as the  source recedes. The classic example of this 
phenomenon (i.e., the Doppler  Effect) explains why we hear a rising pitch 
in the sounding horn of an  approaching automobile and why, when the car 

passes by us and recedes into the  distance, the pitch drops. Ultrasonic Doppler
flow meters use this frequency  shift to work with so-called dirty liquids, 
fluids containing acoustical  discontinuities such as suspended particles, 
entrained gas bubbles or turbulence  vortexes.  
When ultrasound is  beamed through a pipe or tubing containing flowing 
liquid with particles, such a  red blood cells i blood flowing through it, the 
ultrasonic beam (or pulse)  reflects off of the cells with an alteration in 
frequency that is directly  proportional to the flow rate of the liquid in 
the tubing. The ultrasonic  Doppler flow meter then calculates the flow rate 
from the velocity of the red  cells, rather than from the velocity of the 
plasma or other (particle  suspending) liquid.  
Ultrasonic Doppler  flow meters are ideally suited for many applications 
where there is dirty,  particulate rich water (such as sewage) or where there 
are lots of particles or  bubbles such as in slurries, crude oil, and, of 
course, blood. Ultrasonic  Doppler flow meters typically require suspended 
solids or bubbles of at least 5  microns or larger in size to be present in a 
concentration of ~100 parts per  million or higher. Doppler-shift measurement 
doesn't work in liquids with  particulate concentrations exceeding ~45% w/v 
or with high concentrations of  very fine bubbles. Particles or bubbles in 
these size ranges attenuate the  reflected signal until it is 
indistinguishable from tubing background noise.   
From these  considerations its is pretty obvious why neither ultrasonic 
Doppler flow meters  or electromagnetic flow meters were usable in the 
perfusion of cryopatients.   
Why is knowing flow  so important? Obviously, it is important to know 

crudely what the flow through  the patient is. It would be pretty frightening to
have no idea whatsoever of  what the flow rate is during perfusion. But, how 
much precision is necessary and  for what reasons?  
In clinical  perfusion flow is one of a number of critical determinants of 
both oxygen and  substrate delivery to the tissues. Beyond these 

physiologically critical point,  flow, when considered in the context of 
arterial and 
central venous pressures  (i.e., the systemic vascular resistance or SVR) 
provides a wealth of information  about the condition of the patient with 

respect to vascular tone, vascular  compromise (from edema or capillaries 
blocked 
to flow) and it provides a  necessary context for meaningfully evaluating 
critical physiologic parameters  such as the measured gas exchange, pH and 
blood ion content. In cryonics TBW  knowing the flow is important for these 
reasons and for others which are unique  to cryonics.  
Clinical CPB is not  performed in patients who have suffered long agonal 
periods with profound  perimortem systemic ischemia such as that experienced 
by cryopatients. The  impact of such systemic ischemia can be profound and 
may (and usually does)  result either in conditions of very low flow at normal 
physiological pressure  (70 to 90 mm Hg) or conversely astronomically high 
flows at well below such  pressures. The former (we think) results from 

cellular edema compressing  capillaries, intravascular clotting (both macro and
micro) and perhaps from  vasospasm. The latter (we think) results from 
massive systemic vascular  dilation; perhaps as a result of the production of 
large amounts of nitric oxide  (NO) or, in patients with ischemic times of ~30 
min or more, due to substrate  exhaustion in the smooth muscle that controls 
vascular tone. Early attempts in  the late 1960s to place cadavers on CPB 
for organ retrieval failed due to shear  injury from very high blood flow 

rates at barely tolerable physiological  pressures (i.e.,~40-60 LPM at 40 to 60
mm Hg!). I have seen both of these  phenomenon in both experimental animals 
(dogs) and in human cryopatients. So,  for purely practical reasons, it is 
important to know the flow during CPB in  cryopatients. 


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