Arachidonic acid-induced hind limb gangrene : A new experimental rat model of peripheral vascular disease

• Published in: Biological & pharmaceutical bulletin 1999, Vol.22 (3), p.257-260
• Main Authors: TANAKA, T, TAKEI, M, FUKUTA, Y, HIGASHINO, R, FUKUDA, Y, NOMURA, Y, ITO, S, TAMAKI, H, KURIMOTO, T, SUZUKI, Y
• Format: Article
• Language: English
• Subjects: Animals; Arachidonic Acid - toxicity; Aspirin - therapeutic use; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Disease Models, Animal; Disease Progression; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Drug Evaluation, Preclinical; Femoral Artery; Gangrene - chemically induced; Gangrene - pathology; Hindlimb - blood supply; Hindlimb - pathology; Injections, Intra-Arterial; Male; Medical sciences; Platelet Aggregation Inhibitors - therapeutic use; Rats; Rats, Sprague-Dawley; Ticlopidine - therapeutic use; Vascular Diseases - chemically induced; Vascular Diseases - pathology
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.22.257

The purpose of this study was to investigate the characteristics of arachidonic acid-induced peripheral vascular disease in rats. Injecting arachidonic acid (2 mg/leg) into the femoral artery caused hind limb gangrene. Histopathological examination revealed occlusive thrombi and marked vascular injury, including denudation of the endothelium and degeneration of the media in the paw arteries. Arachidonic acid injection markedly enhanced the platelet response to both U-46619 and collagen. Although the number of circulating platelets did not differ between sham-operation rats and arachidonic acid-injected rats, the numbers of circulating white blood cells and red blood cells were raised 10 d after arachidonic acid injection. Thrombocytopenia, induced before arachidonic acid injection, markedly suppressed arachidonic acid-induced hind limb gangrene in rats. In addition, the combined administration of aspirin (100 mg/kg/d, p.o.) and ticlopidine (300 mg/kg/d, p.o.) prevented the progression of arachidonic acid-induced hind limb gangrene. These results suggest that platelets are involved in the progression of arachidonic acid-induced hind limb gangrene. This experimental rat model may be suitable for developing novel drugs for the treatment of peripheral vascular disease.