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. Content-Type: text/html; charset="UTF-8" [ AUTOMATICALLY SKIPPING HTML ENCODING! ] Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=33368