title: Inhibition of chronic vessel wall intimal hyperplasia following acute anticoagulant treatment: relative effects of heparin and dermatan sulphate.
abstract: Surface-bound thrombin which contributes to vessel wall hyperplasia, is resistant to inhibition by heparin/antithrombin III (/ATIII) but not to inhibition by dermatan sulphate/heparin cofactor II (/HCII). To determine the effects of heparin and dermatan sulphate on vessel wall hyperplasia after a first or second injury, rabbit carotid arteries first were injured, using a standard procedure (first injury). Half of the first-injury rabbits were given heparin, dermatan sulphate, or saline, 5 minutes before and at 30-minute intervals over 2 hours post-injury, and then allowed to recover. Four weeks later, the first-injury treated animals were killed and their injured carotid arteries were processed histologically. The remaining untreated first-injury rabbits were also allowed to recover. At 4 weeks, those rabbits were re-anesthetized and their first-injury arteries (which were occluded >75%), were isolated, and vessel wall lumen patency was re-established by endarterectomy (second injury). During this second injury, the animals were treated with heparin, dermatan sulphate, or saline as described above. Four weeks after this second injury, these rabbits were killed and their second injury arteries were processed histologically. Intimal hyperplasia determined histologically, was expressed as an x-fold increase in vessel wall cross-sectional area (i.e., [(media+intima area) media area]). Vessel wall lumen occlusion was expressed as [1-(lumen area/internal elastic lamina area) x 100; % occlusion]. Vessel wall area in the saline-treated animals, increased 2.6+/-1.2 and 2.4+/-1.0 fold respectively, means+/-SD, n = 12, within 4 weeks of the first and second injuries. These increases were due to intimal hyperplasia and associated with 75+/-19% and 79+/-21% occlusion of the vessel wall lumen, respectively. Heparin had little effect, whereas dermatan sulphate (1) decreased hyperplasia by 45% after the first injury and by 47% after the second injury, p<0.008 and <0.03, respectively, and (2) decreased vessel wall occlusion 47+/-12% and 33+/-5% after the first and second injury, respectively. We conclude that (1) dermatan sulphate/HCII may be a useful inhibitor of vessel wall hyperplasia following vessel wall injury, and (2) this effect can be achieved by an acute anticoagulant treatment at the time of injury, unlike heparin/ATIII.
authors.affiliation: Department of Pathology, McMaster University, Hamilton, Ontario, Canada. mbuchan@FHS.McMaster.CA
authors.forename: M R
authors.initials: MR
authors.lastname: Buchanan
authors.forename: S J
authors.initials: SJ
authors.lastname: Brister
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D002339:Carotid Arteries / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D003871:Dermatan Sulfate / Q000627:therapeutic use*; D004108:Dilatation, Pathologic / Q000188:drug therapy; D006493:Heparin / Q000627:therapeutic use*; D006965:Hyperplasia / Q000188:drug therapy; D011817:Rabbits; D017539:Tunica Intima / Q000473:pathology
chemical_list: D000925:Anticoagulants; D003871:Dermatan Sulfate; D006493:Heparin