EFFECTS OF HEPARINOIDS ON THE SCLEROTIC REACTION OF RAT THORACIC AORTA TO INJURY - COMPARISON BETWEEN STANDARD AND LOW-MOLECULAR-WEIGHT HEPARINS IN-VITRO AND IN-VIVO

To assess further the influence of heparinoids on arterial sclerosis, we compared the effects of standard heparin and of a low-molecular-wei ght (low-mol-wt) heparin (CY 216) in vitro on proliferation of culture d arterial smooth muscle cells (SMC) from rat aorta and in vivo on the sclerotic response of rat thoracic aorta to injury with a balloon cat heter (SMC proliferation and deposition of elastin and collagen in the intima-media, using biochemical and histomorphologic techniques). Bot h heparinoids decreased replication of SMC in vitro in a similar dose- dependent manner. In vivo, heparin treatment [continuous intravenous ( i.v.) administration, 60 IU/h/kg body weight (0.35 mg/h/kg)] inhibited all aspects of the aortic reaction for less than or equal to 28 days after injury: synthesis of DNA (early peak of thymidine incorporation into DNA on D3.5); accumulation of DNA, collagen and elastin on D14 an d D28; intimal thickening on D14. An equivalent treatment with CY 216 [60 antiactivated factor X (Xa) IU/h/kg (0.71 mg/h/kg)] exerted simila r though less intense effects on the reaction of intima-media, as asse ssed biochemically, but reduced formation of neointima in a proportion nearly identical to that of heparin. In some respects, which appear t o be related mainly to the fibrotic reaction of aortic media to injury , heparin tended to be a slightly more potent antisclerotic agent than CY 216 although, owing to pharmacokinetic differences, CY 216 had str onger plasma anti-Xa activity than heparin.