Evaluation of the combination of a tissue-type plasminogen activator, SUN9216, and a thromboxane A2 receptor antagonist, vapiprost, in a rat middle cerebral artery thrombosis model.
OBJECTIVE
We aimed to evaluate a modified tissue-type plasminogen activator, SUN9216, and the combination of SUN9216 and a thromboxane A2 receptor antagonist, vapiprost, in a rat middle cerebral artery thrombosis model.


METHODS
Under anesthesia, the left middle cerebral artery was observed under an operation microscope without cutting the dura mater via a subtemporal craniotomy. Photoillumination (wave length, 540 nm) was applied to the middle cerebral artery, and then rose bengal (20 mg/kg) was administered intravenously. The reopening of the middle cerebral artery by SUN9216, injected 30 minutes after middle cerebral artery occlusion, was observed under an operation microscope for a 60-minute observation period. Twenty-four hours after the operation, sections of the cerebrum were stained with triphenyltetrazolium chloride, and the area of cerebral infarction was analyzed by a computer.


RESULTS
The combination of SUN9216 and vapiprost caused reopening of the middle cerebral artery in 58.8% of the rats, which was a greater percentage than that achieved with SUN9216 alone (31.6%). In contrast, saline did not cause reopening of the middle cerebral artery during the 60-minute observation period. The area of cerebral infarction in rats reperfused with SUN9216 was significantly reduced compared with that in the control group. The infarction area in rats treated with the combination of SUN9216 and vapiprost was reduced compared with that in rats treated with SUN9216 alone; this was the case whether or not the occlusion was reperfused. There was a significant correlation between the time of reopening of the middle cerebral artery and area of cerebral infarction.


CONCLUSIONS
A single injection of SUN9216 was effective in recanalizing the vessel and reducing the area of cerebral infarction.
Umemura
K
K
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Wada
K
K
Uematsu
T
T
Nakashima
M
M
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002544:Cerebral Infarction / Q000188:drug therapy / Q000473:pathology; D004195:Disease Models, Animal; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D006538:Heptanoic Acids / Q000494:pharmacology*; D002542:Intracranial Embolism and Thrombosis / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D010960:Plasminogen Activators / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000494:pharmacology
D001713:Biphenyl Compounds; D004338:Drug Combinations; D006538:Heptanoic Acids; D017482:Receptors, Thromboxane; C081981:lanoteplase; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; C060013:vapiprost