Abstract
We evaluated the differences in effects of the competitive inhibitor, argarroban, and the cyclooxygenase inhibitor, aspirin, on the cerebral blood flow (CBF), cerebral energy metabolism, and edema formation following transient forebrain ischemia in mongolian gerbils. Argatroban (3 mg/kg; argatroban-treated group), aspirin (5 mgkg; aspinin-treated group), or saline (saline-treated group) was infused intravenously. CBF was measured continuously and the cerebral specific gravity was evaluated at 120 min after reperfusion. The sequential changes in cerebral energy metabolism, as indicated by the PCr/Pi ratio, β-ATP/Pi ratio and pHi, were also determined. In the argatroban-treated group, the CBF returned more rapidly to the preischemic level after reperfusion as compared to the other groups (recovery time= 19.2 ± 10.6 min), and no reactive hyperemia was observed. Recovery of the CBF in the aspirin-treated group was faster than in the saline-treated group after reperfusion. Decreases in pHi, PCr/Pi, and β-ATP/Pi were observed during bilateral common carotid artery occlusion. The pHi, PCr/Pi ratio, and β-ATP/Pi ratio showed significantly better recovery (p<0.01) in the argatroban-treated group after reperfusion as compared to the other groups. The brain specific gravity in the argatroban-treated group was significantly higher than in the other group (p<0.01). The brain specific gravity in the aspirin-treated group was higher than in the saline-treated group (p<0.01). Argatroban was more effective in ameliorating postischemic cerebral edema than was aspirin (p<0.01). These findings clearly demonstrate that benefical effects of argatroban are greater than those of aspirin following transient forebrain ischemia.
