For the introductory comments on this topic please see the page named: Other Topics
Again, I wish to repeat, this is a discussion website, I feel that this topic addresses an item that clearly would be dangerous and unethical if improperly developed or implemented. I advise that no person or organization should attempt to make any of this item or to implement any part of it for actual use unless that person or organization first obtains all appropriate legal permissions and authorities to do so. In addition, I always advise, this, and all things should always be developed and used in a manner that is safe, reasonable, ethical and appropriate. pg
I want to create a device that will allow an organ for transplantation (example: a kidney) to remain viable outside of the body of the donor and the body of the recipient long enough for the body of the recipient to develop tolerance to the organ so that a rejection will not occur.
The major problem with perfusing organs for transplantation outside of a body is that the perfusing solution cannot deliver enough oxygen to allow the organ to stay viable. I am interested in the physical chemistry feature of pressurizing water that this pressurization increases the oxygen carrying capacity of the water. Actually, water in equilibrium with oxygen at an absolute pressure of 2x atmospheric pressure will have enough dissolved oxygen that this water would transport as much oxygen per ml of fluid as is transported to tissues by normal blood.
I also wish to use as the source of the perfusing fluid the dialysate from normal kidney dialysis patients because this dialysate has the exact necessary physiologic composition to be a perfect fluid to perfuse a kidney that is awaiting transplantation.
The exact configuration of the device would be as follows:
1) that the recipient (who has renal failure and is a standard dialysis patient) would be connected to a standard blood dialysis loop, dialysis would be started, and a portion of the dialysate would be drawn off
2) a pump would raise this drawn off portion of the dialysate to 2x atmospheric pressure (note that 2x atmospheric pressure is a gauge reading of 15 psi, because, by convention, 1 atmosphere is an actual absolute pressure of 15psi, but is read by most pressure gauges as 0 pressure)
3) the drawn off dialysate fluid would be directed to flow over a surface that was surrounded by pure oxygen at 15 psi (the area of this surface would be large enough for the flow rate of the fluid that the fluid would become oxygen saturated to an absolute oxygen pressure of 15 psi)
4) this oxygenated dialysate fluid it would be pumped into the renal artery of the donor kidney via a cannula in that artery and it would perfuse the donor kidney
5) this now deoxygenated dialysate fluid would flow out of the donor kidney’s renal vein and be directed to flow over a surface surrounded by pure nitrogen at 0 psi (this surface would be sufficiently large that the CO2 now present in this dialysate fluid would diffuse out, and this dialysate fluid would, once again, exist at a gauge pressure of 0
6) then this fluid, now purged of the gases of metabolism would be sent back to the return side of the dialysate loop, where it would be introduced into the loop on the recipient side of the semi permeable membrane of the dialysis system so that this fluid would directly re-enter the recipient’s venous blood stream via the standard type dialysis access shunt already present and in use in the recipient as part of the recipient’s regimen of dialysis.
The effect of this configuration would be as follows:
1) the portion of the dialysate drawn off supplies the donor kidney with sufficient oxygen that the kidney does not experience hypoxic damage
2) that the pores of the renal dialysis membranes are sufficiently non-porous that recipient WBC’s do not pass into the dialysate, so that,
3) during the time when a significantly damaging host vs. graft rejection reaction occurs, that the donor kidney could not be significantly damaged by this rejection reaction
4) that the re-perfusion of the fluid from the renal vein fluid of the donor kidney directly back into the venous circulation of the recipient would serve as a source of extensive and varied antigen exposure for the recipient
5) and this ongoing recurrent antigen exposure of the recipient to a variety of biological materials from the donor organ would (hopefully) be a sufficient antigen exposure to create (over time) a tolerance reaction by the recipient
6) that since the composition of the dialysate solution would reflect the physiological and metabolic state of the recipient
7) then this dialysate that is bathing the donor kidney should have the proper physiological parameters to give the donor kidney a very favorable environment for survival and functioning.
8) that is to say, such factors of the dialysate presented to the donor kidney would be proper physiological values for osmolality, pH, ion and glucose concentrations, amino acid levels, fat and triglyceride levels, etc,
9) that these biological materials of daily living contained in the dialysate solution supplied to the donor kidney would be exactly sufficient that they would allow the donor kidney to survive for extended periods without significant injury
10) that the body chemistry control mechanisms of the recipient (because most of the metabolic and physiological feedback control loops in the recipient should be normal) would adjust various nutrient, protein, and other physiologic components of the recipient’s blood (and hence the recipient’s dialysate) to be supportive and reactive to the metabolic needs of the donor kidney
11) and finally, the donor kidney would (hopefully) be sufficiently metabolically active to cleanse the recipient’s blood and produce urine which would be removed from the configuration and thrown away.
The effect would be that the recipient would “tune up” the donor kidney on an as needed basis (hopefully for as long as is needed), and the donor kidney would “tune up” the recipient on an as needed basis (again hopefully for as long as is needed), and the donor kidney could be and would be maintained inside this configuration until the immune reaction of the recipient against the donor kidney came down to sufficiently low enough levels that a transplantation could be performed with a high probability of success.
I feel that this project would require the following steps for implementation:
1) Establishment of an animal research model. The animals would need to be able to have arterio-venous shunts so that blood based dialysis could be performed that is very similar to the dialysis performed in humans.
2) A trial where one of the animal’s kidneys is placed in the configuration to establish the parameters needed for kidney survival where there is no host vs. graft reaction
3) A trial where the animal’s kidney in the configuration becomes the only functioning kidney that the animal has to establish that the kidney in the configuration can act as successfully as a functioning and metabolically active kidney
4) Trials of the situation where the kidney in the configuration is anti-genically different from the animal to see what steps would succeed to get the recipient animal to become tolerant to the kidney in the configuration
5) Episodes where the kidney in the configuration is transplanted into the animal, and thrives as a transplant
6) Once establishment of the feasibility of the configuration via animal testing, then presentation of the data to a properly empowered Human Use Institutional Review Board to generate the protocols for testing the configuration for human use.
7) Once approved by the Human Use Institutional Review Board, then the process of replicating the animal studies in humans, with the exception that a normal human kidney would not be removed for testing in the configuration. Instead, I would suggest that the human related research would begin at the step where a donor kidney is placed in the configuration.
I feel this project would most likely need to go through or at least collaborate with a University and that University’s animal research lab.
I feel that if this project could actually safely preserve the viability of a human organ for transplant outside of a human for an extended period, and especially if this organ could then be safely transplanted with a high probability of successful transplantation without rejection,
Then this project would actually have commercial desirability.
This potential commercial desirability could be used as a springboard to present this project to commercial funding sources where they would be offered patent protection of the configuration and ownership of the concept for marketing and commercial implementation purposes.
Other issues to consider with this configuration would be whether the donor organ would need to be a kidney, but instead could be other needed organs such as: hearts, lungs, pancreas, marrow, etc.
The marrow issue is particularly intriguing because one worrisome issue with the configuration would be protecting the configuration and the donor organ from infection.
It would certainly be feasible to direct the flowing fluid in the configuration to channels where the fluid could receive high level ultraviolet irradiation. This could serve as a mechanism to keep the fluid sterile or at least with very low bacteria and virus counts, as long as the irradiation did not pose a threat to create molecules in the fluid that were toxic.
I feel that the ultraviolet irradiation action on the fluid most likely would not serve well as a control against bacteria lodged in colonies inside the donor organ.
The thought that arises however, is to create inside the configuration an area of a “matrix or net” created from inert materials, and place on (or in) this matrix area an aliquot of the marrow of the person who was the donor.
The question arises whether this aliquot of marrow would survive and thrive in this hyperbaric oxygen environment, and would it create WBC’s and/or other components of effective immunity ?
If viability of the marrow cells occurred, would the entrained marrow serve as an ongoing and sustained source of WBC’s and other immune related materials to actually “float out” into the solution?
If the marrow were located “upstream” from the donor organ, would these WBC’s and other items of immunity then perfuse the donor organ and act to scavenge away infection from within the donor organ?
And finally, if this aliquot of donor marrow did become a source area to continuously supply the configuration with cells and other biologically active materials that would serve to protect the donor organ and the configuration from infection, would this immune competency then “leak out” over to the recipient and create problems of a significant donor vs. host reaction ?
As we know, these questions lend themselves to basic research for their answers.
It is my hope that the induction of tolerance principle that is present in this configuration would markedly decrease the need for absolute antigen compatibility (HLA testing, etc.) between the donor and the recipient.
One major hoped for benefit of this configuration (apart from its ability to extend the life of organs for transplantation as they await implantation), is that this configuration may enable any particular donor to serve as a successful donor to any particular recipient.
If it was feasible as I described it, wouldn’t this configuration be a good thing to create, and think how much happiness it could supply to that portion of human society with a transplantation need.
I am happy to reply in more detail if you want. And, of course, you may forward this discussion to whatever groups or organizations that you feel may be able to implement it.