I guess the goal isn’t to achieve perfect perfusion, but simply to reduce the number of red blood cells in the brain while cooling the brain, to avoid clotting and slow ischemic damage. In the case of an emergency deployment of such a device, you’re already going to experience significant ischemia, one way or another. Though I can see how embolisms could be catastrophic. I don’t know if it would be possible to make such a device simple enough to be operated by an amateur while still being safe to use.
Blood clotting is not caused by red blood cells but by platelets. They do get caught up by the clot spreading around them and then act as parts of the barrier, but removing them too fast would actually increase ischemia because they’re what carry the oxygen.
(By the way, I hope that the cryoprotectant solutions contain high concentrations of dissolved oxygen. Not nearly as good as having the actual RBCs, but you can increase the amount (supersaturation) by keeping it under pressure.)
Anyways, given that perfusion is already taking place (and this is removing all of the components of the blood including the platelets), the other option is to disable the blood clotting cascade, for example by administration of anticoagulants such as warfarin. I don’t know if this is already done. You would also have access to more “extreme” types of anticoagulation, chemicals (or higher doses) that aren’t on the medical market because the effects are normally too strong.
I suppose another option would be to suggest that the patient to start taking anticoagulants before death. I’m not sure whether that would have legal implications though.
Blood clotting is not caused by red blood cells but by platelets.
I thought ischemic tissue caused RBCs to form Rouleaux complexes. Even without RBC’s, ischemia causes plenty of changes that have effects functionally equivalent to clotting: Swelling of myocytes and the endothelium, subsarcolemmal and endothelial blebs, et cetera.
I suppose another option would be to suggest that the patient to start taking anticoagulants before death. I’m not sure whether that would have legal implications though.
This is certainly helpful and doesn’t seem to have been done in past patients, but we’re mostly talking about unexpected settings here, where no standby is available. I don’t think it has any legal implications, at least the Best’s article doesn’t mention any.
See the third paragraph of Coagulation—the diagram of the blood clotting cascade is on the right. I’ve never heard of rouleaux having a role in blood clotting—a quick PubMed search turned up this case study, but it was due to mutations in the protein fibrinogen.
I don’t think it has any legal implications, at least the Best’s article doesn’t mention any.
I was thinking that since the drugs are dangerous (even more so if you’re already in a weakened condition), it would be viewed as attempting to hasten their death. Especially if someone overdosed either deliberately or accidentally.
As long as you recognize that clotting is a different process. =)
It’s been a few years since I studied this, but as far as I know, the physiological significance of rouleaux (including whether they block blood vessels) is unknown—don’t forget that they’re in equilibrium with the non-rouleaux form. Although cold temperatures will slow down that equilibrium, and possibly cause the problems you’re referring to.
As long as you recognize that clotting is a different process. =)
Of course.
It’s been a few years since I studied this, but as far as I know, the physiological significance of rouleaux (including whether they block blood vessels) is unknown—don’t forget that they’re in equilibrium with the non-rouleaux form.
I wouldn’t know, but Mike Darwin says they are harmful:
[...] irregular aggregation of RBCs rouleaux formation has a profound negative impact on perfusion.
I would have been much more convinced by data from a controlled experiment. A lot of things could cut off flow, as you pointed out, and there are a lot of things going wrong in a dying person. I’m actually not sure why he brought rouleaux into it—my understanding is that we already know the RBCs clump and that this blocks capillaries.
In any case, the main point I was trying to make was that reducing the number of RBCs in the brain is probably not the best way to go, unless we can figure out an alternative way to supply oxygen. Destroying the RBCs and letting the hemoglobin travel freely would probably help, but that would set off all sorts of damaging physiological responses as well.
The diameter of the average RBC is ~7.7μ, about 1μ larger than the diameter of the average brain capillary. In order for RBCs to pass through capillaries it is necessary for them to deform (and in so doing place the maximum amount of surface area in contact with the vascular endothelium to facilitate gas exchange). RBC deformability is critically dependent upon RBC intracellular adenosine triphosphate (ATP) concentration being adequate. With periods of ischemia of ~ 7 minutes, RBCs become depleted of ATP and become rigid, making passage through brain capillaries more difficult (higher arterial pressure required) or impossible.
In-house research conducted by the author has demonstrated that the cerebral microcirculation remains profoundly compromised for 30-60 minutes following reperfusion, even when circulation is restored using cardiopulmonary bypass. Brain parencymal and endothelial cell swelling, as well as changes in the zeta potential of the red blood cells, may all be contributing to the extensive blood sludging and microvascular stasis observed after reperfusion following 10 minutes of global normothermic ischemia in the laboratory.
I already read it. That quote doesn’t say anything about rouleaux or clotting; it just describes one of the mechanisms (other than clotting) by which brain ischemia occurs. Can you be more specific?
I guess the goal isn’t to achieve perfect perfusion, but simply to reduce the number of red blood cells in the brain while cooling the brain, to avoid clotting and slow ischemic damage. In the case of an emergency deployment of such a device, you’re already going to experience significant ischemia, one way or another. Though I can see how embolisms could be catastrophic. I don’t know if it would be possible to make such a device simple enough to be operated by an amateur while still being safe to use.
Blood clotting is not caused by red blood cells but by platelets. They do get caught up by the clot spreading around them and then act as parts of the barrier, but removing them too fast would actually increase ischemia because they’re what carry the oxygen.
(By the way, I hope that the cryoprotectant solutions contain high concentrations of dissolved oxygen. Not nearly as good as having the actual RBCs, but you can increase the amount (supersaturation) by keeping it under pressure.)
Anyways, given that perfusion is already taking place (and this is removing all of the components of the blood including the platelets), the other option is to disable the blood clotting cascade, for example by administration of anticoagulants such as warfarin. I don’t know if this is already done. You would also have access to more “extreme” types of anticoagulation, chemicals (or higher doses) that aren’t on the medical market because the effects are normally too strong.
I suppose another option would be to suggest that the patient to start taking anticoagulants before death. I’m not sure whether that would have legal implications though.
I thought ischemic tissue caused RBCs to form Rouleaux complexes. Even without RBC’s, ischemia causes plenty of changes that have effects functionally equivalent to clotting: Swelling of myocytes and the endothelium, subsarcolemmal and endothelial blebs, et cetera.
This is certainly helpful and doesn’t seem to have been done in past patients, but we’re mostly talking about unexpected settings here, where no standby is available. I don’t think it has any legal implications, at least the Best’s article doesn’t mention any.
See the third paragraph of Coagulation—the diagram of the blood clotting cascade is on the right. I’ve never heard of rouleaux having a role in blood clotting—a quick PubMed search turned up this case study, but it was due to mutations in the protein fibrinogen.
I was thinking that since the drugs are dangerous (even more so if you’re already in a weakened condition), it would be viewed as attempting to hasten their death. Especially if someone overdosed either deliberately or accidentally.
They block blood vessels and prevent perfusion, which is why it’s equivalent to clotting.
As long as you recognize that clotting is a different process. =)
It’s been a few years since I studied this, but as far as I know, the physiological significance of rouleaux (including whether they block blood vessels) is unknown—don’t forget that they’re in equilibrium with the non-rouleaux form. Although cold temperatures will slow down that equilibrium, and possibly cause the problems you’re referring to.
Of course.
I wouldn’t know, but Mike Darwin says they are harmful:
I would have been much more convinced by data from a controlled experiment. A lot of things could cut off flow, as you pointed out, and there are a lot of things going wrong in a dying person. I’m actually not sure why he brought rouleaux into it—my understanding is that we already know the RBCs clump and that this blocks capillaries.
In any case, the main point I was trying to make was that reducing the number of RBCs in the brain is probably not the best way to go, unless we can figure out an alternative way to supply oxygen. Destroying the RBCs and letting the hemoglobin travel freely would probably help, but that would set off all sorts of damaging physiological responses as well.
Read the linked article.
I already read it. That quote doesn’t say anything about rouleaux or clotting; it just describes one of the mechanisms (other than clotting) by which brain ischemia occurs. Can you be more specific?