Method of determining that an organ is not suitable for transplantation and using it for testing substances
An organ perfusion apparatus and method monitor, sustain and/or restore viability of organs and preserve organs for storage and/or transport. Other apparatus include an organ transporter, an organ cassette and an organ diagnostic device. The method includes perfusing the organ at hypothermic and/or normothermic temperatures, preferably after hypothermic organ flushing for organ transport and/or storage. The method can be practiced with prior or subsequent static or perfusion hypothermic exposure of the organ. Organ viability is restored by restoring high energy nucleotide (e.g., ATP) levels by perfusing the organ with a medical fluid, such as an oxygenated cross-linked hemoglobin-based bicarbonate medical fluid, at normothermic temperatures. During the period in which the organ is preserved and/or maintained, various drug research and development may be performed on and/or with the organ. The organ may be perfused with a fluid containing a substance such as a test substance to obtain data regarding the organ, the substance and an interaction of the substance and the organ. The data may then be used to ultimately provide information regarding the drugs efficacy in support of regulatory filings for new drugs.
1. A method of determining effects of a substance on at least one organ, comprising:
restoring and/or maintaining organ viability of the at least one organ, wherein the restoring and/or maintaining of the organ viability includes perfusing the organ with at least one medical fluid during at least one perfusion mode to restore and/or maintain pre-ischemia energy and enzyme levels of the organ;
sensing tissue and/or fluid characteristics indicative of organ viability by a sensor to obtain diagnostic data;
analyzing the diagnostic data to determine whether the at least one organ is suitable to be transplanted; and
based on a determination that the at least one organ is not suitable to be transplanted, further comprising:
perfusing the at least one organ with a first medical fluid to preserve the at least one organ;
contacting the at least one organ with at least one test substance; and
gathering data regarding at least one of the at least one organ, the at least one test substance, and interaction between the at least one organ and the at least one test substance.
2. The method of claim 1 , further comprising:
generating measurement data based on the sensed characteristics; and
comparing the measurement data to characteristics of the at least one test substance.
3. The method of claim 1 , wherein the contacting step includes perfusing the organ with a second medical fluid containing the test substance.
4. The method of claim 3 , wherein the first and second medical fluids are the same.
5. The method of claim 3 , wherein the first and second medical fluids are different.
6. The method of claim 3 , further comprising collecting the second medical fluid that has passed through the at least one organ from an organ bath and sensing characteristics of the collected medical fluid indicative of the interaction between the at least one organ and the test substance by a sensor.
7. The method of claim 3 , wherein the test substance is a chemical compound.
8. The method of claim 3 , wherein the test substance is at least one of natural and modified antibodies.
9. The method of claim 3 , wherein the test substance is an immunotoxin.
10. The method of claim 3 , wherein the second medical fluid is blood.
11. The method of claim 1 , wherein the sensor monitors at least one of the at least one organ and an effluent from the organ.
12. The method of claim 11 , wherein the data are generated and displayed in real time, stored, transmitted to a remote site, transferred to a recording medium, or relayed to a microprocessor for assessment.
13. The method of claim 11 , wherein the sensed characteristics relate to at least one of absorption, distribution, metabolism and excretion.
14. The method of claim 11 , wherein the sensed characteristics relate to at least one of pharmacokinetics, pharmacodynamics and toxicity.
15. The method of claim 11 , wherein the sensed characteristics relate to at least one of determining what the substance is doing to the at least one organ and what the at least one organ is doing to the substance.
16. The method of claim 11 , further comprising:
generating measurement data based on the sensed characteristics; and
comparing the measurement data to characteristics of the at least one test substance.
17. The method of claim 11 , further comprising:
generating measurement data based on the sensed characteristics; and
comparing the measurement data to characteristics of a normal organ.
18. A method of screening at least one organ, comprising:
restoring and/or maintaining organ viability of the at least one organ, wherein the restoring and/or maintaining of the organ viability includes perfusing the organ with at least one medical fluid during at least one perfusion mode to restore and/or maintain pre-ischemia energy and enzyme levels of the organ;
sensing tissue and/or fluid characteristics indicative of organ viability by a sensor to obtain diagnostic data;
analyzing the diagnostic data to determine whether the at least one organ is suitable to be transplanted; and
based on a determination that the at least one organ is not suitable to be transplanted, further comprising:
perfusing the at least one organ with a first medical fluid to preserve the organ;
contacting the at least one organ with at least one test substance; and
gathering data regarding at least one of the at least one organ, the at least one test substance, and interaction between the at least one organ and the at least one test substance,
wherein the at least one test substance is a bioactive agent.
19. The method of claim 16 , further comprising:
generating measurement data based on the sensed characteristics; and
comparing the measurement data to characteristics of a normal organ.