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

Ann Surg. 2000 Jun;231(6):789-94. doi: 10.1097/00000658-200006000-00002.

Abstract

Objective: 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.

Summary background data: SNAD is a delivery agent that potentiates the gastrointestinal absorption of LMWH.

Methods: 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.

Results: 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.

Conclusion: 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.

MeSH terms

  • 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
  • Swine
  • Vena Cava, Inferior*
  • Venous Thrombosis / drug therapy*

Substances

  • Anticoagulants
  • Heparin, Low-Molecular-Weight