Effects of unilateral intrathecal administrations of low dose tissue-type plasminogen activator on clot lysis, vasospasm and brain phospholipid hydroperoxidation in a primate model of bilateral subarachnoid hemorrhage.
In order to clarify the effect of clot lysis by recombinant tissue-type plasminogen activator (tPA) on the brain lipid peroxidation, we measured phosphatidylcholine hydroperoxide (PCOOH) and phosphatidylethanolamine hydroperoxide (PEOOH) levels in a primate model of subarachnoid hemorrhage (SAH). Monkeys were assigned into two groups; a tPA-treated group receiving intrathecal injections of 0.02 mg tPA, and a placebo-treated group receiving saline. The tPA or placebo was injected into the right side of the basal cistern every 8 h for 6 days following bilateral SAH induction. The tPA cleared the right side clots (p < 0.0001), but not the left side clots. The degree of vasospasm in the right middle cerebral artery and the rCBF decrease in the right parietal cortex were significantly attenuated in the tPA group (p < 0.05). In the placebo group, more severe vasospasm and marked rCBF reduction were noted in comparison with those in the tPA group. PCOOH levels in the parietal cortex were significantly higher in the placebo group than in the tPA group (p < 0.05). There were no significant changes in brain PEOOH levels. These results may explain the limitations for clinical application of unilateral intrathecal administration of tPA.
Suzuki
H
H
Department of Neurosurgery, Mie University School of Medicine, Japan.
Kanamaru
K
K
Kuroki
M
M
Sun
H
H
Waga
S
S
Miyazawa
T
T
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D007839:Functional Laterality / Q000502:physiology; D007278:Injections, Spinal; D002546:Ischemic Attack, Transient / Q000188:drug therapy*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008251:Macaca; D008252:Macaca fascicularis; D010743:Phospholipids / Q000378:metabolism; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy*; D013927:Thrombosis / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
D005343:Fibrinolytic Agents; D010743:Phospholipids; D010959:Tissue Plasminogen Activator