A chemiluminescent detection of superoxide radical produced by adherent leucocytes to the subendothelium following thrombolysis: studies with a photochemically induced thrombosis model in the guinea pig femoral artery.
Reocclusion following thrombolysis is a major limitation of thrombolytic therapy with recombinant tissue-type plasminogen activator (rt-PA) because denuded vessel wall exposed to blood following thrombolysis is a favourable surface for platelet and leucocyte deposition. We have applied a chemiluminescence technique to detect superoxide radical (0(-2)) produced by leucocytes adherent to the femoral artery 24 h after photochemically induced thrombogenesis in the guinea pig in vivo and subsequent thrombolysis by rt-PA. Intravenous administration of MCLA, a specific chemiluminescence reagent for detecting O(-2), markedly increased photon emission. the photon emission was markedly potentiated by phorbol myristate acetate and was suppressed by superoxide dismutase. Reocclusion 24 h after rt-PA induced thrombolysis was observed in 10 of 16 animals. Histological observations revealed extensive polymorphonuclear leucocytes adherent to the vessel wall at the site of thrombogenesis and thrombolysis. A higher level of 0(-2) could be detected from the arteries in which thrombolysis was induced compared with those without thrombolysis. Further, the level 0(-2) detected was greater in reoccluded arteries compared with those in which reflow was established. These observations suggest that 0(-2) is produced by adherent leucocytes at the site of thrombolysis and that leucocytes are involved in reocclusion after thrombolysis.
Wada
K
K
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Umemura
K
K
Nishiyama
H
H
Saniabadi
A R
AR
Takiguchi
Y
Y
Nakano
M
M
Nakashima
M
M
D000818:Animals; D002448:Cell Adhesion; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism*; D005263:Femoral Artery / Q000378:metabolism* / Q000473:pathology; D006168:Guinea Pigs; D007093:Imidazoles; D008027:Light; D008163:Luminescent Measurements; D008297:Male; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D010960:Plasminogen Activators / Q000627:therapeutic use*; D011719:Pyrazines; D011994:Recombinant Proteins / Q000627:therapeutic use; D012395:Rose Bengal / Q000633:toxicity; D013481:Superoxides / Q000378:metabolism*; D015912:Thrombolytic Therapy; D013927:Thrombosis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
D007093:Imidazoles; D011719:Pyrazines; D011994:Recombinant Proteins; D013481:Superoxides; C063412:2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo(1,2-alpha)pyrazin-3-one; D012395:Rose Bengal; D010960:Plasminogen Activators