The efficacy of non-lactate-generating metabolites as substrates for maintaining donor tissues.
The study was conducted to investigate effectiveness of non-lactate-generating metabolites as substrates for maintaining donor tissues. beta-hydroxybutyrate was selected for the study, with the cornea as the experimental model. Parameters included the effect on growth of corneal cells, retention of metabolic activity of human and rabbit corneas under storage, and the integrity of the endothelium and physiological function of the cornea in vivo. The experiments revealed that beta-hydroxybutyrate enhances the growth of all three cell types of rabbit corneas, with an optimal concentration estimated at about 12-15 mM of D,L-racemic mixture. It is more efficient than glucose for elevating the tissue energy charge. When stored in an NaHCO3-free isotonic medium supplemented with beta-hydroxybutyrate at 4 degrees C, lactate production and accumulation in the cornea were reduced by > 85% and metabolic activity was retained at a markedly high level for at least 11 days, as opposed to about 3 days when stored in McCarey-Kaufman medium. When beta-hydroxybutyrate in a balanced salt solution was infused into the anterior chamber, the cornea performed its physiologic function normally without NaHCO3 and no remarkable postoperational changes in morphology and density of endothelial cells were evident. In conclusion, the findings of this study suggest that non-lactate-generating metabolites are efficient substrates for donor tissues. No NaHCO3 supplement is needed when beta-hydroxybutyrate is used. The solution is therefore stable in pH, and thereby favorable for clinical applications.
Chen
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Chen Ophthalmic Laboratories, Baltimore, Maryland 21131.
Chen
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D020155:3-Hydroxybutyric Acid; D000227:Adenine Nucleotides / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003315:Cornea / Q000187:drug effects / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D006885:Hydroxybutyrates / Q000494:pharmacology*; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009926:Organ Preservation / Q000379:methods*; D010101:Oxygen Consumption / Q000187:drug effects; D011817:Rabbits; D013997:Time Factors; D014019:Tissue Donors
D000227:Adenine Nucleotides; D006885:Hydroxybutyrates; D007773:Lactates; D005947:Glucose; D020155:3-Hydroxybutyric Acid