Evaluation of eight preservation solutions for endothelial in situ preservation.
BACKGROUND
Non-heart-beating donors (NHBDs) have the potential to reduce the increasing numbers of patients on kidney and liver graft waiting lists. One problem observed with kidneys obtained from NHBDs is the endothelial injury seen on protocol core biopsies after implantation. We postulate that this is caused by a combination of warm ischemia, cold ischemia, and hypertonic citrate during in situ preservation (ISP) rather than hypothermic machine preservation. Our aim was to optimize ISP methods to preserve endothelial structure and function.


METHODS
An animal model of ISP was used to compare the ability of eight different preservation solutions to protect mammalian vascular tissue exposed to a combination of warm and cold ischemia. Smooth muscle contractile function and endothelial dependent relaxation (nitric oxide production) were determined using an organ bath method.


RESULTS
Bretchneider's HTK solution preserved the ability of endothelial tissue to relax vascular tissue in response to acetylcholine (91% relaxation vs. 17% saline control; ANOVA, P<0.001); in stark contrast, Marshall's solution performed no better than saline (15% relaxation vs. 17% saline control, P=NS). UW solution (80%) and a derivative lacking the starch colloid (70%) were comparable with HTK. Belzer-MPS (55%), Celsior (57%), and Perfadex (44%) showed a roughly equivalent level of endothelial preservation. Electron microscopy confirmed an anatomical loss of structure correlating with loss of function.


CONCLUSIONS
ISP requires a large volume of fluid to be pumped at high flow rates. In this model, HTK retained a powerful ability to preserve endothelial structure and function during warm ischemia.
The Liver/Renal Unit, The Freeman Hospital, Newcastle-upon-Tyne, United Kingdom. c4moon@doctors.org.uk
Colin H
CH
Wilson
Gerard
G
Stansby
Malcolm
M
Haswell
Anne C
AC
Cunningham
David
D
Talbot
D000241:Adenosine / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology*; D005978:Glutathione / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008297:Male; D023421:Models, Animal; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D011887:Raffinose / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D014021:Tissue Preservation
D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose