Experimental thrombosis model induced by free radicals. Application to aspirin and other different substances.
A large number of experimental studies suggests that oxygen free radicals play a major role in the pathogenesis of the myocardial lesions observed during the sequence ischemia-reperfusion. The purpose of this study was to determine whether oxygen free radicals can induce thrombosis. In so doing we have developed a new experimental thrombosis model. Reproducible focal thrombosis has been achieved by irradiating mesenteric arterioles of rat for variable time with green filtered light issuing from a mercury lamp after systemic injection of different rose bengal doses. The number of emboli that remove in the blood (N), the duration of total occlusion (T) and the number of emboli per minute were then measured. As control, no rose bengal administration was done and the vessels were exposed to the filtered light. In comparison with this control, results clearly showed that free radicals always induced thrombosis and the induced thrombus was mainly composed of platelets. In this new thrombosis model induced by free radicals antithrombotic drugs (aspirin, 200 mg/Kg, heparin, 2 mg/Kg) and antioxidants (vitamin C, 10 and 20 mg/Kg, allopurinol, 200 and 300 mg/Kg, vitamin E, 500 and 1000 mg/Kg) have been tested. Results have shown that only heparin and vitamin E had an antithrombotic effect on thrombus formation induced by free radicals. This model should be useful in studying the effects of different drugs and could lead to new treatment modalities for ischemic accident and other cardiovascular diseases.
D000493:Allopurinol / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001160:Arterioles; D001205:Ascorbic Acid / Q000494:pharmacology / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005609:Free Radicals; D006493:Heparin / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008641:Mesenteric Vascular Occlusion / Q000139:chemically induced* / Q000188:drug therapy / Q000517:prevention & control; D008853:Microscopy / Q000295:instrumentation; D010100:Oxygen / Q000633:toxicity*; D010777:Photochemistry; D051381:Rats; D017208:Rats, Wistar; D012395:Rose Bengal / Q000008:administration & dosage / Q000528:radiation effects / Q000633:toxicity*; D026082:Singlet Oxygen; D014743:Videotape Recording / Q000295:instrumentation; D014810:Vitamin E / Q000494:pharmacology / Q000627:therapeutic use
D000975:Antioxidants; D005343:Fibrinolytic Agents; D005609:Free Radicals; D014810:Vitamin E; D026082:Singlet Oxygen; D012395:Rose Bengal; D000493:Allopurinol; D006493:Heparin; D001205:Ascorbic Acid; D001241:Aspirin; D010100:Oxygen