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
A. Chajara et al., 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, Journal of cardiovascular pharmacology, 23(6), 1994, pp. 995-1003
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.