Effect of Suleparoide on Fibrinolysis in the Anterior Chamber of Rabbits

Abstract

Intra-ocular fibrin deposition following ocular surgery is a serious postoperative complication. The current management of severe postoperative fibrin response is usually ineffective. A quantitative model of fibrin deposition in the rabbit anterior chamber was used to assess the efficacy of Suleparoide I.N.N. (HHS-5) in preventing fibrin formation and in promoting the clearance of fibrinous membranes. Citrated human plasma was injected intracamerally after paracentesis to induce the formation of fibrin clots: 10 min or 24 h after plasma injection, solutions of HHS-5 at different concentrations were injected into the anterior chamber of rabbits. Intra-ocular HHS-5 injection 10 min after plasma injection prevented the formation of fibrinous membranes in a dose-dependent fashion in almost all treated animals. When HHS-5 was injected at 24 h after fibrin clot formation, a reduction of clot areas was observed but the membranes did not completely disappear. No evidence of ocular toxicity was detected by slit-lamp bio microscopy, intra-ocular pressure and corneal thickness measurements. On the basis of the results obtained with the present animal model, HHS-5 appears as an effective and safe agent for the prevention of fibrinous membrane formation. The data suggest a potential use of HHS-5 for the prophylaxis of fibrin formation in human eyes undergoing extensive intraocular surgery, or in diabetic patients where a hypercoagulable state may be present.

The Heparan Sulfate Suleparoide Inhibits Rat Corneal Angiogenesis and in vitro Neovascularization

“…Furthermore, repeated local administration of corticosteroids may lead to a clinically important increase of intraocular pressure, with possible damage of optic nerve, and to a posterior subcapsular cataract during long-term therapy (American Medical Association, 1995). Indeed, suleparoide is endowed of a favorable toxicity profile in animal models (Lepri et al, 1996), confirming the potential utilization in ocular treatments for humans.…”

“…Suleparoide has been introduced as an antithrombotic agent, with weak anticoagulant effects primarily mediated through the activation of the heparin cofactor-II, but not antithrombin-III (Callas et al, 1993b). The heparan sulfate suleparoide prevents fibrinous membrane formation in the anterior chamber of rabbits after human plasma injection with no evidence of ocular toxicity (Lepri et al, 1996).…”