Effect of Low-Molecular-Weight Heparins on Laser-Induced Thrombus Formation in Rat Mesenteric Vessels

Abstract

Laser-induced thrombi have been frequently produced in rat mesenteric vessels to investigate the effect of antithrombotic drugs. We have tested low molecular heparins in comparison to unfractionated heparin. The investigations were carried out on male Wistar rats weighing 200–300 g; the animals were anesthetized with pentobarbital sodium (Nembu-tal®) 60 mg/kg i.p. Vascular lesions were induced with a Coherent CR-2 supergraphite ion laser (argon laser) mounted on a Leitz Orthoplan microscope. An intestinal loop was spread on a self-constructed object stage, mounted on the microscope table. The laser beam was directed through the optical path of the microscope on small mesenteric vessels in the fat-free portion of the mesentery. For the evaluation of thrombus formation the number of laser injuries needed to induce a defined thrombus was used. All low-molecular-weight heparins (preparation B, Braun; BR-Z-0601, Braun; CY 216, Choay; Fragmin, Kabi; low molecular heparin, Sandoz and Org 10172, Organon) or unfractionated heparin (Liquemin®; Hoffmann-La Roche) showed a significant and dose-dependent antithrombotic effect after subcutaneous injection, if venules had been damaged. The effect lasted for 48 h, partly for over 48 h. If thrombus formation was studied after intravenous injection into arterioles as well as into venules 8 h after injection, no antithrombotic effect could be demonstrated under the influence of CY 216 or unfractionated heparin.

Stability of thrombosis induced by electrocoagulation of rat middle cerebral artery.

“…For a 20-to 30-/xm-diameter mesenteric vessel, pulses of 120 mWx67 milliseconds were effective; one such pulse produced a small thrombus, and three to five repetitions at 1-minute intervals produced a thrombus that half-filled the vessel. 25 In our study, when electrocoagulation was used to produce a "permanent" block of blood flow in the MCA, it did not do so. With a maximal nonhemorrhagic electrocoagulation, we observed only a temporary occlusion, which lasted for less than 4 hours.…”

“…24 Histological evaluation indicated that the endothelium was severely damaged by this procedure. 23 Lasers have also been used, both experimentally 25 and clinically 21 -26 ;ĉ ritical parameter, as in the neurosurgical studies, was found to be temperature. For a 20-to 30-/xm-diameter mesenteric vessel, pulses of 120 mWx67 milliseconds were effective; one such pulse produced a small thrombus, and three to five repetitions at 1-minute intervals produced a thrombus that half-filled the vessel.…”

Antithrombotic Effects of Three Thrombin Inhibitors in a Rat Model of Laser-Induced Thrombosis

“…Comparison of the efficacy of the throm bin inhibitors studied with that of heparin revealed that much higher doses of heparin were necessary to obtain the same anti thrombotic effect in the 'rat model of laserinduced thrombosis' [25].…”

Effects of a Supersulfated Low Molecular Weight Heparin (IK-SSH) on Different Hemostatic Parameters

“…In animal experiments some SSH exerted a much stronger antithrombotic effect than their parent compounds, while the anticoagulant effects are equal or slightly higher [17][18][19]. Thus SSH because of their long-lasting antithrombotic effects might be well-suited to prevent thromboembolic episodes in highrisk patients.…”

“…A supersulfated LMWH (IK-SSH) has been developed by Iketon Farmaceutici, Milan and has been extensively tested in different animal toxicologic studies and in models of animal thrombosis [18][19][20]. We report here on a phase I clinical trial on the tolerance of IK-SSH and its effects on various hemostatic parameters in healthy volunteers.…”