Periadventitial delivery of heparin in the prevention of microvenous thrombosis.
OBJECTIVE
In spite of advances in technique and instrumentation, microvascular free tissue transfer remains associated with a persistent risk of flap failure. The use of systemic anticoagulants to overcome the formation of vasoocclusive thrombi at reactive anastomotic sites is associated with a high rate of flap hematoma and is ill advised in the operative setting. The purpose of this study was to investigate the use of a biodegradable, nontoxic polymer gel (polyvinyl alcohol, PVA) to effect a sustained localized release of perivascular heparin around thrombogenic venous anastomoses.


METHODS
A modified adventitial inclusion model was created in the femoral vein of 64 adult female Sprague-Dawley rats. Animals were divided into four experimental groups: 1) no treatment (controls), 2) periadventitial PVA gel contained in a vicryl chamber, 3) periadventitial PVA gel mixed with heparin, and 4) systemic heparin (intravenous pump). Patency rates in the femoral vein were checked at 10 minutes, 1 hour, 1 day, and 4 days after surgery. Systemic coagulation parameters and histology (scanning electron microscopy, SEM) were assessed in representative animals from all groups.


RESULTS
Patency rates for experimental groups showed a significant improvement in animals treated with PVA/heparin and systemic heparin over controls. Wound hematomas occurred in 7 of 16 animals in group 3, and in 4 of 16 animals in group 4. Activated partial thromboplastin times were elevated in group 4 only (> 150 seconds).


CONCLUSIONS
Continuous release of periadventitial heparin using a polymeric delivery system may represent an efficient means of attenuating the reactivity of microvenous anastomoses without affecting systemic coagulation parameters. In this model, however, its use was associated with a high rate of local wound hematoma.
Hirigoyen
M B
MB
Mount Sinai Hospital, New York, NY, USA.
Zhang
W X
WX
Weinberg
H
H
Buchbinder
D
D
D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000009:adverse effects; D005260:Female; D006083:Graft Occlusion, Vascular / Q000517:prevention & control*; D006406:Hematoma / Q000209:etiology; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use*; D015918:Infusion Pumps, Implantable; D008855:Microscopy, Electron, Scanning; D011098:Polyglactin 910; D011142:Polyvinyl Alcohol / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013524:Surgical Flaps / Q000009:adverse effects / Q000379:methods* / Q000502:physiology; D013924:Thrombophlebitis / Q000517:prevention & control*; D014654:Vascular Patency
D000925:Anticoagulants; C058382:heparin-polyvinyl alcohol hydrogel; D011098:Polyglactin 910; D011142:Polyvinyl Alcohol; D006493:Heparin