X-Message-Number: 2801 Date: 03 Jun 94 21:18:51 EDT From: Mike Darwin <> Subject: SCI.CRYONICS Henson Alcor Case Report Keith Henson notes in his recent commentary on the last Alcor perfusion: <<We were very near our target when perfusion was terminated by loss of arterial pressure. This is something we have seen before. Since there was no jump in perfusate loss it was almost certainly due to heart valves starting to leak as they were deformed by glycerol dehydration--something we have seen in a number of suspensions.>> Without being in any way recriminatory or negative I wish to simply point out that this observation is not correct and does not represent either my experiences with or without Jerry Leaf in caring for either Alcor or non-Alcor patients. I would make the following points: 1) The heart valves are incompetent (i.e., leaky) under static load from the start of perfusion in either in the presence or the absence of cryoprotectant. This is a well known phenomenon in bypass and it is one of the major reasons why the left ventricle is ALWAYS vented when the heart is not beating and the ventricle is not opened; otherwise the LV becomes grossly distended and seriously damaged due to due to equilibration of pressure (arterial) across the "leaky" aortic valve. (This is why Jerry Leaf and I routinely vented the LV on whole body patients.) Normally this leakage is not physiologically significant in the beating heart because the ventricle is "unloaded" by contracting and pumping. Keep in mind these are BIOLOGICAL systems (valves) not industrial ones and some degree of regurgitation is acceptable under physiologic conditions. 2) Contrary to Keith's statement that loss of arterial pressure is routine or common during the tail-end of cryoprotective perfusion, the REVERSE is the case; mean arterial (and central venous) pressures RISE as glycerol concentration increases near the end of the CPA ramp. This happens due to the fact that the viscosity of the perfusate increases as the glycerol concentration rises (and as the temperature is sometimes reduced concomitantly to minimize toxcicity, further increasing viscosity). The increased viscosity means increased resistance to flow which in turn means increased pressure. This is usually compensated for by the perfusuionist manually DECREASING the arterial flow rate. 3) I am at a bit of a disadvantage here in that the Alcor Board has (at least so far) decided to withold all patient records from me and bar me from completing the case histories on the patients I cared for while at Alcor both before I became suspension team leader and after. As a consequence I have only limited patient data to draw from. I would note that the following is typical: A neuropatient started out perfusing at a flow rate of 850 cc/min and a mean arterial pressure (MAP) of 50 mmHg. During the early period of glycerolization the MAP dropped to approx. 30 mmHG due to tissue dehydration (which increases capillary diameter and decreases vascular resistance). As glycerol concentration exceeds 1M the arterial pressure starts to rise. By the end of perfusion of this patient the MAP is about 50 mmHG and the flow has been decreased to about 450 cc/min. (Case report A-1049). A similar pattern is seen in cases A-1068, A-1133, A-1260, A-1082 and A-1234. Similarly, the two ACS cases I have done exhibited a similar (but more pronounced) pattern of MAP increase with glycerolization since we were perfusing to far higher terminal glycerol concentrations in these cases: i.e., 6 to 6.5 M vs. 3 to 4 M for the previously cited Alcor cases. In fact, terminal MAP on the last ACS case was 131 mmHg at a flow rate of 950 cc/min up from 62 mmHg and a flow rate of 1350 cc at the start of cryoprotective perfusion. Failure of the brain to swell is NOT indicative of continuing cerebral perfusion. The only ways I know of to assess whether brain perfusion is continuing is to do one of the following: a) inject a dye into the perfusate and watch through the burr-hole and look for cerebral cortical staining with the dye. b) inject radiopaque or radioactive material and do either angiography or a brain scan to determine the presence/absence and/or distribution of flow. c) Perfuse the oxygenator with radioactive Xenon and look at Xenon distribution/clearance times in the brain. Please note I am not actively recommending the above (particularly not b or c), merely noting that these are the only approaches I know of. I have used the dye approach with Alcor patients (I developed it) and found it very useful (I have used both fluroscein green and fluroscein labeled dextran isothiocyanate and illuminated the cortical surface with UV light to determine perfusate distribution). The sudden loss of arterial pressure during cryoprotective is NOT a normal course of affairs and in my opinion represents a serious (and in this case) unexplained compromise of the intergrity of either the arterial leg (i.e., high pressure side) of the circulatoruy system/perfusion circuit. I have perfused MANY rabbits, dogs, cats and humans to high terminal glycerol concentrations (3-7+ M) and have never observed this phenomenon. Finally, I urge that the current embargo on patient raw data be ended and that such data be made available to all who request it (with appropriate steps taken to protect patient confidentiality). BPI intends to follow this policy and will shortly be posting the technical case historires/raw data on all three of the patients it has treated to date (one case report has been ready for several weeks and will be posted shortly). Respectfully, Mike Darwin Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=2801