Arachidonic acid-induced hind limb gangrene: a new experimental rat model of peripheral vascular disease.
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.
Tanaka
T
T
Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., Saitama, Japan.
Takei
M
M
Fukuta
Y
Y
Higashino
R
R
Fukuda
Y
Y
Nomura
Y
Y
Ito
S
S
Tamaki
H
H
Kurimoto
T
T
Suzuki
Y
Y
D000818:Animals; D016718:Arachidonic Acid / Q000633:toxicity*; D001241:Aspirin / Q000627:therapeutic use; D004195:Disease Models, Animal; D018450:Disease Progression; D004353:Drug Evaluation, Preclinical; D005263:Femoral Artery; D005734:Gangrene / Q000139:chemically induced* / Q000473:pathology; D006614:Hindlimb / Q000098:blood supply* / Q000473:pathology; D007269:Injections, Intra-Arterial; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013988:Ticlopidine / Q000627:therapeutic use; D014652:Vascular Diseases / Q000139:chemically induced* / Q000473:pathology
D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D013988:Ticlopidine; D001241:Aspirin