Efficacy of organ preservation media enriched with nonlactate-generating substrate for maintaining tissue viability: a transplantation study.
BACKGROUND
Previously, isotonic solution (IS) enriched with beta-hydroxybutyrate, a nonlactate-generating substrate, was shown to be efficacious in maintaining tissues' ATP and metabolic activity under cold storage. The objective of this study was to verify these findings in terms of tissue viability in vivo.


METHODS
Using a rabbit cornea transplantation model, efficacy of IS was studied and compared with McCarey-Kaufman medium, with or without beta-hydroxybutyrate, and other known media (Optisol and Likorol), with different properties and without beta-hydroxybutyrate. After storage at 4 degrees C for 6, 7, and 11 days, the corneas were grafted, and postoperative changes in corneal thickness, and endothelial cell density and morphology were monitored with a pachymeter and specular microscope.


RESULTS
The experiments revealed that before grafting, IS effectively controlled tissue swelling for 7 days or longer, comparable to Optisol. When grafted, the IS-stored corneas deturgesced at high rates, with a short half-time (t1/2) for the de-swelling process, and the grafts remained thin and clear with an intact endothelium. This reflects excellent tissue viability. In the controls, the deturgescence process was extremely sluggish, with significantly lower rates and longer t1/2 (P= >0.01-0.05). Immediate swelling for 3-5 days after grafting was also observed with Optisol. These grafts had significant endothelium cell loss of 24-30% after 12 weeks (P= >0.01-0.02).


CONCLUSIONS
IS is more efficacious than currently used media for sustaining the viability of donor corneas under cold storage. These findings may serve as a useful basis for future tests of IS in other organ storage systems.
Chen
C H
CH
Chen Laboratories, Baltimore, Maryland 21131, USA.
Rama
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P
Chen
S C
SC
Sansoy
F N
FN
D020155:3-Hydroxybutyric Acid; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002470:Cell Survival; D002809:Chondroitin Sulfates; D045424:Complex Mixtures; D003315:Cornea / Q000166:cytology*; D016039:Corneal Transplantation; D016895:Culture Media, Serum-Free; D003911:Dextrans; D004727:Endothelium / Q000166:cytology; D005839:Gentamicins; D006885:Hydroxybutyrates; D019188:Organ Preservation Solutions; D011817:Rabbits
D045424:Complex Mixtures; D016895:Culture Media, Serum-Free; D003911:Dextrans; D005839:Gentamicins; D006885:Hydroxybutyrates; D019188:Organ Preservation Solutions; D000255:Adenosine Triphosphate; D002809:Chondroitin Sulfates; C075736:Optisol; D020155:3-Hydroxybutyric Acid