title: Argatroban attenuates leukocyte- and platelet-endothelial cell interactions after transient retinal ischemia.
abstract: OBJECTIVE
  Argatroban, a direct thrombin inhibitor, has been shown to reduce neural injury after transient cerebral ischemia. It has also been reported that this neuroprotective effect results from an anticoagulant function. This study was designed to evaluate quantitatively the inhibitory effects of argatroban on leukocyte- and platelet-endothelial cell interactions after transient retinal ischemia.
  
  
  METHODS
  Retinal ischemia was induced for 60 minutes in male Long-Evans rats by temporary ligation of the optic sheath (n=342). Argatroban was administered just after induction of ischemia. Leukocyte and platelet behavior in the retinal microcirculation was then evaluated in vivo with scanning laser ophthalmoscopy. The expression of P-selectin and intracellular adhesion molecule-1 (ICAM-1) was evaluated by reverse transcription-polymerase chain reaction. After 10 days of reperfusion, ischemia-induced retinal damage was evaluated histologically.
  
  
  RESULTS
  Treatment with argatroban suppressed leukocyte-endothelial cell interactions; the maximum numbers of rolling and accumulated leukocytes were reduced by 90.1% (P<0.05) and 58.7% (P<0.05), respectively, at 12 hours after reperfusion. Treatment with argatroban also suppressed platelet-endothelial cell interactions; the maximum numbers of rolling and adhering platelets were reduced by 91.8% (P<0.01) and 78.9% (P<0.01), respectively, at 12 hours after reperfusion. The expression of P-selectin and ICAM-1 mRNA was suppressed significantly in the argatroban-treated retinas (P<0.01). Histologic examination demonstrated the protective effect of argatroban on ischemia-induced retinal damage (P<0.01).
  
  
  CONCLUSIONS
  Argatroban treatment suppressed leukocyte- and platelet-endothelial cell interactions after transient retinal ischemia. This inhibitory effect on postischemic blood cell-endothelial cell interactions might partially contribute to its neuroprotective effects.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawaramachi Sakyo-ku, Kyoto-shi, Kyoto, 606-8507, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Miyahara
authors.forename: Junichi
authors.initials: J
authors.lastname: Kiryu
authors.forename: Akitaka
authors.initials: A
authors.lastname: Tsujikawa
authors.forename: Hideto
authors.initials: H
authors.lastname: Katsuta
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nishijima
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamashiro
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nonaka
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Honda
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D015870:Gene Expression / Q000187:drug effects; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007511:Ischemia / Q000188:drug therapy*; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D008297:Male; D019007:P-Selectin / Q000235:genetics; D010314:Partial Thromboplastin Time; D010875:Pipecolic Acids / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011517:Prothrombin Time; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D015424:Reperfusion; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012164:Retinal Diseases / Q000188:drug therapy* / Q000503:physiopathology; D012171:Retinal Vessels / Q000187:drug effects / Q000503:physiopathology; D013449:Sulfonamides; D013917:Thrombin / Q000037:antagonists & inhibitors; D016896:Treatment Outcome; D014654:Vascular Patency / Q000187:drug effects
chemical_list: D019007:P-Selectin; D010875:Pipecolic Acids; D010975:Platelet Aggregation Inhibitors; D012333:RNA, Messenger; D013449:Sulfonamides; D018799:Intercellular Adhesion Molecule-1; D001120:Arginine; D013917:Thrombin; C031942:argatroban