Membrane stabilization in harvested vein graft storage: effects on adhesion molecule expression and nitric oxide synthesis.
OBJECTIVE
Expression of cellular adhesion molecules in human saphenous vein grafts may occur even during harvesting and storage, before the grafts have been implanted as bypass conduits. This may play a role in graft adaptation to arterial flow conditions, which may play an important role in late graft patency. In this study, ketotifen, a mast cell membrane stabilizing agent was studied for its effects on reducing endothelial reactivity during storage of harvested vein graft segments.


METHODS
Human saphenous vein grafts, obtained from seven patients and then divided into two equal parts of control and study specimens, were stored in either heparinized blood (Group A) or heparinized blood containing 100 microg/ml ketotifen (Group B) for 1 h at room temperature. Specimens were analyzed by Western blotting to quantify ICAM-1, E-selectin, P-selectin, VCAM-1, and inducible nitric oxide synthase (NOS-2) expression, as well as tissue cGMP levels in response to topical application of an endothelium-independent vasodilator.


RESULTS
ICAM-1, E-selectin and P-selectin expression did not differ between the groups. However, VCAM-1 expression was significantly lower in Group B (460 +/- 29 vs. 289 +/- 50, P = 0.01). NOS-2 expression (488 +/- 64 vs. 577 +/- 38, P = 0.02) and tissue cGMP levels (2.2 +/- 0.6 pmol/ml vs. 5.7 +/- 1.7 pmol/ml, P = 0.01) in response to nitroglycerin (24 +/- 10% vs. 11 +/- 5%, P = 0.02) were higher in Group B.


CONCLUSIONS
Of all of the adhesion receptors studied, only VCAM-1 expression was reduced by a mast cell membrane-stabilizing agent, perhaps because of activation of the venous endothelium during harvest prior to ketotifen exposure. However, ketotifen also augmented NOS-2 expression, increased tissue cGMP levels in response to nitroglycerin. These actions may improve vascular homeostasis in the venous graft, suggesting the possibility that this strategy may improve long-term graft patency.
Vural
K M
KM
Department of Cardiothoracic Surgery, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. kvural@tr-net.net.tr
Oz
M C
MC
Liao
H
H
Batirel
H F
HF
Pinsky
D J
DJ
D000925:Anticoagulants / Q000494:pharmacology; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D001026:Coronary Artery Bypass; D015925:Cryopreservation; D006152:Cyclic GMP / Q000096:biosynthesis; D004338:Drug Combinations; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006493:Heparin / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007665:Ketotifen / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D009926:Organ Preservation; D019007:P-Selectin / Q000096:biosynthesis; D012501:Saphenous Vein / Q000187:drug effects / Q000378:metabolism* / Q000637:transplantation; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D000925:Anticoagulants; D015815:Cell Adhesion Molecules; D004338:Drug Combinations; D019040:E-Selectin; D006634:Histamine H1 Antagonists; D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D006493:Heparin; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D006152:Cyclic GMP; D007665:Ketotifen