Jvd. Gryflowczowski et al., COLD-STORAGE OF RABBIT THORACIC AORTA IN UNIVERSITY-OF-WISCONSIN SOLUTION REDUCES ENDOTHELIUM-INDEPENDENT VASODILATION, Journal of Pharmacy and Pharmacology, 49(11), 1997, pp. 1096-1101
Optimum preservation conditions for storage of donor livers and blood
vessels are essential for successful transplantation. The blood vessel
s are used as vascular conduits to facilitate anastomosis of the liver
to the recipient's systemic vasculature. Failure of some transplants
has been ascribed to thrombosis of these vascular conduits possibly be
cause of alterations in vascular reactivity owing to inadequate storag
e techniques. To restrict data variability previously associated with
studies using a heterogeneous sample of vessels from man, this study i
nvestigated changes in vascular reactivity in segments of rabbit thora
cic aorta from male, age-matched, New Zealand White rabbits stored at
4 degrees C in either University of Wisconsin solution (UW; Du Pont Ph
armaceuticals, UK) or Krebs-Bulbring buffer (KB). Percent vasodilation
to acetylcholine remained significantly greater in UW than in KB at -
log (M) concentrations of 7.0 (UW = 47.05 +/- 4.26 compared with KB =
13.20 +/- 7.20%; P < 0.001), 6.5 (UW = 66.82 +/- 4.83 compared with KB
= 26.60 +/- 9.48%; P < 0.01), and 6.0 (UW = 83.68 +/- 5.26 compared w
ith KB = 31.20 +/- 9.83%; P < 0.001). This was not significantly diffe
rent to relaxation in unstored arteries and suggested improved endothe
lial function and structure, confirmed by electron microscopy. Percent
vasodilation to sodium nitroprusside was significantly lower in UW th
an in unstored (D-0) arteries at -log (M) concentrations of 7.5 (D-0 =
28.27 +/- 4.02 compared with UW = 15.21 +/- 1.82%; P < 0.01), 7.3 (D-
0 = 52.58 +/- 5.05 compared with UW = 29.23 +/- 1.94%; P < 0.01), 7.0
(D-0 = 69.70 +/- 4.85 compared with UW = 49.72 +/- 2.49%; P < 0.05), a
nd 6.4 (D-0 = 93.16 +/- 2.93 compared with UW = 71.29 +/- 5.20%; P < 0
.05). Percent vasodilation was also lower in UW-compared with KB-store
d arteries at -log (M) sodium nitroprusside concentrations of 7.0 (UW
= 49.72 +/- 2.49 compared with KB = 64.11 +/- 5.03%; P < 0.05) and 6.4
(UW = 71.29 +/- 5.20 compared with KB = 96.91 +/- 5.96; P < 0.05). El
ectron microscopy confirmed that this was not a result of degradation
of smooth muscle structure. The nitric oxide synthase inhibitor L-N-G-
nitro-L-arginine methyl ester (100 mu M) did not significantly modulat
e sodium nitroprusside-induced vasodilation in unstored arteries, when
endothelial function was maximum, or in UW-stored arteries, suggestin
g that the reduced responses in UW-stored arteries were not because of
increased synthesis of nitric oxide. This reduced relaxation to sodiu
m nitroprusside was therefore nitric oxide-independent and not a resul
t of competition between sodium nitroprusside and endothelial 'nitric
oxide donation' for cGMP. In summary, cold-storage preservation with U
W reduced endothelium-independent vascular relaxation by mechanisms ot
her than competition with NO; this requires further evaluation.