 |
 |

Inhibitors of Nitric Oxide Promote Microvascular Thrombosis
Babak Azizzadeh, MD;
Georgette M. Buga, PhD;
Gerald S. Berke, MD;
Babak Larian, MD;
Louis J. Ignarro, PhD;
Keith E. Blackwell, MD
Arch Facial Plast Surg. 2003;5:31-35.
Background Microvascular free tissue transfer is a widely utilized method of head and neck reconstruction. Despite advances in the field, reports of experienced microvascular surgeons on large series of free flap procedures reveal that the incidence of free flap failure varies between 5% and 9%. Most cases of free flap failure are initiated by platelet-mediated events that result in thrombosis at the microvascular anastomoses. Recent evidence indicates that nitric oxide (NO) plays a critical role in preventing thrombosis by inhibiting platelet adhesion and aggregation. The role of NO in microvascular anastomotic thrombosis has not been studied.
Objective To determine the role of NO in microvascular thrombosis using an in vivo rabbit model.
Methods An arterial inversion graft (AIG)induced microvascular thrombosis model was utilized in New Zealand white rabbits. The femoral arteries were used bilaterally to create 3-mm AIGs. Intravenous NO donor, NO inhibitor, or isotonic sodium chloride solution (control) was administered for 1 hour following the completion of the AIG, and vessel patency was then checked using a direct "milking test." Sixteen rabbits (32 AIGs) were used as controls. A potent NO inhibitor, N(w)-nitro-L-arginine methylester (L-NAME), was administered to 13 rabbits (26 AIGs) and L-arginine, a NO precursor/donor, was given to 10 rabbits (20 AIGs).
Results The control animals had a thrombosis rate of 46.9%. The rate of thrombosis in animals exposed to an NO inhibitor (L-NAME) was significantly higher, at 76.9% (P<.05, 2 = 4.23). The L-arginine group did not show a statistical difference with the control in the rate of thrombosis (50.0%).
Conclusions Nitric oxide plays a role in microvascular anastamotic thrombosis. Intravenous NO inhibitors appear to increase the short-term rate of microvascular thrombosis. L-arginine, an NO precursor, does not appear to produce the opposite effect. Further studies using local NO donors and antagonists as well as more potent NO precursors are needed to further evaluate NO's role in microvascular thrombosis. The results of this study may have applications to human microvascular surgery.
From the Division of Head and Neck Surgery (Drs Azizzadeh, Berke, Larian, and Blackwell) and the Department of Molecular and Medical Pharmacology (Drs Buga and Ignarro), UCLA School of Medicine, Los Angeles, Calif.
|