Membrane stabilization in harvested vein graft storage: effects on adhesion molecule expression and nitric oxide synthesis

• Published in: European journal of cardio-thoracic surgery Vol. 16; no. 2; pp. 150 - 155
• Main Authors: Vural, Kerem M., Oz, Mehmet C., Liao, Hui, Batirel, Hasan F., Pinsky, David J.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Science B.V 01.08.1999; Elsevier Science
• Subjects: Adhesion molecule; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anticoagulants - pharmacology; Biological and medical sciences; Blotting, Western; Cell Adhesion Molecules - biosynthesis; Clinical death. Palliative care. Organ gift and preservation; Coronary Artery Bypass; Cryopreservation; Cyclic GMP - biosynthesis; Drug Combinations; E-Selectin - biosynthesis; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Enzyme-Linked Immunosorbent Assay; Heparin - pharmacology; Histamine H1 Antagonists - pharmacology; Humans; Intercellular Adhesion Molecule-1 - biosynthesis; Ketotifen - pharmacology; Medical sciences; Membrane stabilizer; Nitric oxide; Nitric Oxide - biosynthesis; Nitric Oxide Synthase - biosynthesis; Nitric Oxide Synthase Type II; Organ Preservation; P-Selectin - biosynthesis; Reoperation; Saphenous; Saphenous Vein - drug effects; Saphenous Vein - metabolism; Saphenous Vein - transplantation; Vascular Cell Adhesion Molecule-1 - biosynthesis; Vein graft; Saphenous; Vein graft; Reoperation; Adhesion molecule; Membrane stabilizer; Nitric oxide; Human; Organ preservation; Saphenous vein; Ketotifen; Cell adhesion molecule; Antagonist; Gene expression; H1 Histamine receptor; In vitro
• ISSN: 1010-7940; 1873-734X
• DOI: 10.1016/S1010-7940(99)00128-1

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 μg/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.