The effect of tranexamic acid on cochlear blood flow in guinea pigs measured by laser Doppler flowmetry.

OBJECTIVE: This study investigated the vasoactive effect of tranexamic acid on the cochlear blood flow in guinea pigs. METHOD: 3 ml solution (infusion speed, 0.5 ml/min) containing different concentrations of tranexamic acid was intravenously infused into 15 guinea pigs under general anesthesia. The guinea pigs were grouped according to four levels of dosage of the medicine (470 mg/kg, n=6; 220 mg/kg, n=3; 4 mg/kg, n=3; 1 mg/kg, n=3). Before administering medicine, saline solution was administered in similar volume and speed as a control. The cochleas were surgically exposed and laser Doppler flowmetry monitored cochlear blood flow volume (CBF). The left femoral artery was cannulated to permit a transducer to monitor systemic blood pressure (BP). RESULTS: (1) Stimulatory effect of tranexamic acid on CBF was dose-dependent at concentrations of 1-470 mg/kg and, (2) the time course of changes in CBF was almost identical to that in BP following tranexamic acid administration. CONCLUSION: Preliminary findings suggest that intravenous administration of tranexamic acid increases CBF due to vasomotorial mechanism effect on BP.

[Studies on attenuation of post-ischemic brain injury by kampo medicines-inhibitory effects of free radical production. II].

It is thought that highly reactive oxygen radicals generated at the ischemia-reperfusion in case of strokes play an important role in damaging the brain. It is well known that lipid peroxidation is propagated by active oxygen radicals, and the the brain is susceptible to the lipid peroxidation. In the previous study, we found that several Chinese herbal medicines and kampo components, which were used for the attenuation of the post-ischemic brain injury, showed a free-radical (OH., O2-. and DPPH) scavenging activity. However, it is not clear whether these Chinese herbal medicines can inhibit the lipid peroxidation reaction or not. In attempting to address this question, we have used three kinds of kampo formulations (Oren-gedoku-to (Huang-Lian-Jie-Du-Tang), Saiko-ka-ryukotsu-borei-to (Chai-Hu-Jia-Long-Gu-Mu-Li-Tang) and Keishi-bukuryo-gan (Gui-Zhi-Fu-Ling-Wan)) to measure the suppressive effect of the lipid peroxidation on the mouse cerebrum using the TBA technique in vitro and in vivo. In vitro experiments, all these Chinese herbal medicines decreased the levels of TBA-reactive substances concentration-dependently. In vivo studies, the levels of the TBA-reactive substance of the cerebrum homogenate of mice treated with these kampo formulations by p.o. for three weeks also decreased. From these results, we suggest that the pharmacological action of Chinese herbal medicines used for the attenuation of the post-ischemic brain damage not only have a free-radical scavenging activity, but also have a suppressive effect on the generation of the lipid peroxidation.

[Studies on attenuation of post-ischemic brain injury by kampo medicines-inhibitory effects of free radical production. I].

In view of the recent investigation, highly reactive oxygen-derived free radicals may play a role in cerebral ischemia and brain damage, free radical scavenging activity of kampo formulations (Oren-gedoku-to, Keishi-bukuryogan, Saiko-ka-ryukostu-borei-to and Daio-botampi-to) and Kampo components (Ityou, Shini, Menamomi, Arinosudama and Denshiti), used for the attenuation of brain damage, was investigated in vitro. The used experimental system was a radical scavenging action against 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide anion radical (O2-.) and hydroxyl radical (OH.) by the electron spin resonance technique at room temperature. All kampo formulations and kampo components showed radical scavenging activity in a concentration-dependent manner. This result indicates that kampo formulations, treated for brain damage, were good radical scavenger that could possibly prevent ischemic complications such as formation of brain damage. The intensity of scavening activity of kampo formulations for three types of radicals were as follows; 1. DPPH: Daio-botampi-to > Saiko-ka-ryukotsu-borei-to = Keishi-bukuryo-gan > Oren-gedokuto, 2. O2-.: Daio-botampi-to = Keishi-bukuryo-gan > Saiko-ka-ryukotsu-borei-to > Oren-gedoku-to, 3. OH.: Daio-botampi-to = Saiko-ka-ryukotsu-borei-to > Keishi-bukuryo-gan = Oren-gedoku-to. Daio-botampi-to indicated the strongest scavenging activity against three types of radicals. Ischemic brain damage is thought to be an "oketsu" syndrome, which is correlated with abnormalities of the microcirculation. Therefore, Daio-botampi-to, which has been used for "oketsu" syndrome, showed superior free-radical scavenging activity.