Comparative study on the use of anticoagulants heparin and recombinant hirudin in a rabbit traumatic anastomosis model.
Antithrombotic drugs, such as heparin, have been used in the clinics for a long time. Heparin acts by binding with antithrombin III to form a complex thereby enhancing the activity of antithrombin III to inactivate coagulation factors IIa, IXa, Xa, XIa and XIIa. Hirudin is a new antithrombotic agent and is reported to be much more powerful than heparin on a gravimetric basis. When both are administered systemically, one of the common complications seen is bleeding. Some previous studies have shown that local vascular endothelial concentrations of heparin are 30 to 7500 times greater than those found in the circulating blood. In order to avoid such complications, topical administration of antithrombotic drugs may be an ideal route of administration. The rabbit ear arterial crush-avulsion thrombosis model was used in this study. The animals were divided into five groups: one control group and four treatment groups which received varying concentrations of heparin and hirudin. In the saline control group, the patency rate was 19.23% at 24 hrs and 15.38% at 7 days. A higher patency rate at 7 days was obtained in groups treated with high concentration of heparin and hirudin. ACT, PT and APTT performed on samples drawn one hour after drug administration were within the normal range in both the control and the treatment groups. Scanning electron microscopy revealed the different extent of the clots on the injured intimal surfaces of the vessels in different groups. The results indicate that high concentrations of topically administered heparin or hirudin minimize the systemic complications and maximize the antithrombotic effects.
Fu
K
K
Department of Surgery, Loyola University Chicago Stritch School of Medicine, Maywood, IL 60153, USA.
Izquierdo
R
R
Walenga
J M
JM
Fareed
J
J
D000287:Administration, Topical; D000714:Anastomosis, Surgical; D000818:Animals; D001158:Arteries / Q000293:injuries* / Q000601:surgery*; D004357:Drug Synergism; D004431:Ear, External / Q000098:blood supply / Q000293:injuries; D006470:Hemorrhage / Q000517:prevention & control; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D024764:Hirudin Therapy; D006629:Hirudins / Q000008:administration & dosage / Q000633:toxicity; D008297:Male; D008855:Microscopy, Electron, Scanning; D008866:Microsurgery; D011183:Postoperative Complications / Q000517:prevention & control*; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D016037:Single-Blind Method; D017695:Soft Tissue Injuries / Q000601:surgery; D013927:Thrombosis / Q000517:prevention & control*; D014654:Vascular Patency / Q000187:drug effects*; D014947:Wounds and Injuries
D006629:Hirudins; D011994:Recombinant Proteins; D006493:Heparin