Cold-storage of rabbit thoracic aorta in University of Wisconsin solution reduces endothelium-independent vasodilation.
Optimum preservation conditions for storage of donor livers and blood vessels are essential for successful transplantation. The blood vessels 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 because of alterations in vascular reactivity owing to inadequate storage techniques. To restrict data variability previously associated with studies using a heterogeneous sample of vessels from man, this study investigated changes in vascular reactivity in segments of rabbit thoracic aorta from male, age-matched, New Zealand White rabbits stored at 4 degrees C in either University of Wisconsin solution (UW; Du Pont Pharmaceuticals, UK) or Krebs-Bülbring 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 with KB = 31.20 +/- 9.83%; P < 0.001). This was not significantly different to relaxation in unstored arteries and suggested improved endothelial function and structure, confirmed by electron microscopy. Percent vasodilation to sodium nitroprusside was significantly lower in UW than in unstored (D0) arteries at -log (M) concentrations of 7.5 (D0 = 28.27 +/- 4.02 compared with UW = 15.21 +/- 1.82%; P < 0.01), 7.3 (D0 = 52.58 +/- 5.05 compared with UW = 29.23 +/- 1.94%; P < 0.01), 7.0 (D0 = 69.70 +/- 4.85 compared with UW = 49.72 +/- 2.49%; P < 0.05), and 6.4 (D0 = 93.16 +/- 2.93 compared with UW = 71.29 +/- 5.20%; P < 0.05). Percent vasodilation was also lower in UW- compared with KB-stored 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). Electron microscopy confirmed that this was not a result of degradation of smooth muscle structure. The nitric oxide synthase inhibitor L-NG-nitro-L-arginine methyl ester (100 microM) did not significantly modulate sodium nitroprusside-induced vasodilation in unstored arteries, when endothelial function was maximum, or in UW-stored arteries, suggesting that the reduced responses in UW-stored arteries were not because of increased synthesis of nitric oxide. This reduced relaxation to sodium nitroprusside was therefore nitric oxide-independent and not a result of competition between sodium nitroprusside and endothelial 'nitric oxide donation' for cGMP. In summary, cold-storage preservation with UW reduced endothelium-independent vascular relaxation by mechanisms other than competition with NO; this requires further evaluation.
Gryf-Lowczowski
J V
JV
Department of Surgery, King's College School of Medicine and Dentistry, Rayne Institute, London, UK.
Sherlock
D
D
Salisbury
J
J
Benjamin
I S
IS
Alexander
B
B
D000109:Acetylcholine / Q000494:pharmacology*; D000241:Adenosine / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D015925:Cryopreservation; D004730:Endothelium, Vascular / Q000187:drug effects*; D005978:Glutathione / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008855:Microscopy, Electron, Scanning; D009638:Norepinephrine / Q000494:pharmacology; D019188:Organ Preservation Solutions; D011817:Rabbits; D011887:Raffinose / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D002314:Cardioplegic Solutions; D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D014662:Vasoconstrictor Agents; D000493:Allopurinol; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose; D000109:Acetylcholine; D009638:Norepinephrine