Treatment of experimentally induced caval thrombosis with oral low molecular weight heparin and delivery agent in a porcine model of deep venous thrombosis

• Published in: Annals of surgery 2000-06, Vol.231 (6), p.789-794
• Main Authors: Salartash, K, Lepore, M, Gonze, M D, Leone-Bay, A, Baughman, R, Sternbergh, 3rd, W C, Bowen, J C, Money, S R
• Format: Article
• Language: English
• Subjects: Animals; Anticoagulants - administration & dosage; Disease Models, Animal; Drug Delivery Systems; Enteral Nutrition; Evaluation Studies as Topic; Female; Heparin, Low-Molecular-Weight - administration & dosage; Intestinal Absorption; Random Allocation; Scientific Papers; Swine; Vena Cava, Inferior; Venous Thrombosis - drug therapy
• ISSN: 0003-4932; 1528-1140
• DOI: 10.1097/00000658-200006000-00002

This experiment evaluated enterally administered low molecular weight heparin (LMWH) combined with sodium N-[10-(2-hydroxybenzoyl)amino] decanoate (SNAD) for the treatment of induced venous thrombosis. SNAD is a delivery agent that potentiates the gastrointestinal absorption of LMWH. Forty female pigs were equally assigned to four groups: control (saline); enteral LMWH, 2,000 IU/kg; enteral SNAD, 50 mg/kg; and enteral LMWH, 2,000 IU/kg and SNAD, 50 mg/kg. Under fluoroscopic guidance, the infrarenal vena cava was occluded with a balloon catheter. Two milliliters of ethanol was injected into the distal vena cava. The inflated balloon catheter remained in situ for 5 days, at which time animals angiographically exhibiting thrombus were randomly assigned to the four groups. Study medications were dosed at 12-hour intervals by means of a gastrostomy tube placed previously. After 7 days of treatment, thrombus was extracted. A separate group of 10 animals was used to measure plasma antifactor Xa levels for 6 hours after enteral dosing of LMWH/SNAD. The amount of residual thrombus after treatment with enteral LMWH/SNAD was significantly decreased. Antifactor Xa levels were significantly elevated in the LMWH/SNAD group versus baseline. The combination of enterally administered LMWH and SNAD given for 7 days appeared to decrease caval thrombosis in this model of deep vein thrombosis. Enteral LMWH/SNAD effected an increase in plasma levels of antifactor Xa.