Hemorheological abnormalities in experimental cerebral ischemia and effects of protein kinase inhibitor on blood fluidity.
The aim of this study was to investigate the mechanisms of the pathogenesis of hyperviscosity following cerebral ischemia. Focal ischemia was produced by embolic occlusion of the right middle cerebral artery (MCA) in rats for 1 hour, followed by recirculation. Twenty-four hours after MCA occlusion, fasudil, a protein kinase inhibitor, was administered intraperitoneally. Blood samples were taken from the abdominal aorta, and viscosity was measured using a cone-plate viscometer. The viscosity of whole blood in the ischemic attack group was significantly increased compared with the sham operated group 24 hours after MCA occlusion. Fasudil dose-dependently and significantly decreased the blood viscosity, and reduced to the normal range after administration of 10 mg/kg of fasudil (sham-operated rats, 5.17+/-0.05 cP; pre dose/ischemic rats, 6.05+/-0.08 cP; post dose/ischemic rats, 5.23+/-0.14 cP; 37.5 sec(-1)). Our findings suggest that cerebral ischemia induces a potent, systemic and long-lasting hyperviscosity, and that the inhibition of protein kinases, especially rho kinase, is efficacious in preventing this hyperviscosity.
Hitomi
A
A
Laboratory for Pharmacology, Asahi Chemical Industry, Tagata-Gun, Japan.
Satoh
S
S
Ikegaki
I
I
Suzuki
Y
Y
Shibuya
M
M
Asano
T
T
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000097:blood / Q000201:enzymology / Q000209:etiology; D001809:Blood Viscosity / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology; D006400:Hematocrit; D006438:Hemodilution; D002546:Ischemic Attack, Transient / Q000097:blood* / Q000201:enzymology / Q000209:etiology; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D020768:Middle Cerebral Artery / Q000601:surgery; D009553:Nimodipine / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D051381:Rats; D017208:Rats, Wistar; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D008689:Methacrylates; D047428:Protein Kinase Inhibitors; D009553:Nimodipine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D013930:Thromboxane-A Synthase; C034364:ozagrel; C049347:fasudil