Reversal of Delayed Vasospasm by TS-011 in the Dual Hemorrhage Dog Model of Subarachnoid Hemorrhage
L. Hacein-Beya,b,
D.R. Harderd,
H.T. Meiera,
P.N. Varelasb,c,
N. Miyataf,
K.K. Lauere,
J.F. Cusickb and
R.J. Romand
a Division of Neuroradiology, Department of Radiology, Medical College of Wisconsin, Milwaukee, Wis
b Departments of Neurological Surgery, Medical College of Wisconsin, Milwaukee, Wis
c Neurology, Medical College of Wisconsin, Milwaukee, Wis
d Physiology, Medical College of Wisconsin, Milwaukee, Wis
e Anesthesiology, Medical College of Wisconsin, Milwaukee, Wis
f Medicinal Research Laboratories, Taisho Pharmaceutical Co., Saitama, Japan
View larger version (95K):
[in a new window]
|
Fig 1. Representative sequential angiograms obtained in a dog after induction of the dual hemorrhage model of SAH. The left panel presents the control angiogram before induction of SAH. The middle panel depicts the diameter of the basilar artery 3 days after the first cisternal injection of blood. The right panel depicts the appearance of the basilar artery 3 days after the second cisternal injection of blood. The arrow indicates the narrowest point in the basilar artery, which shows vasospasm where sequential measurements were made.
| |
View larger version (10K):
[in a new window]
|
Fig 2. Graph shows the time course of changes in the diameter of the basilar artery after induction of the dual hemorrhage model of SAH in dogs. The numbers in parentheses indicate the number of dogs studied at each time point. The asterisk indicates a significant difference in the diameter of the basilar artery at day 4 (*) and day 7 (**) versus the control diameter measured before the induction of SAH.
| |
View larger version (8K):
[in a new window]
|
Fig 3. Graph shows the time course of changes in the concentration of 20-HETE in CSF following induction of the dual hemorrhage model of SAH in dogs. The numbers in parentheses indicate the number of dogs studied at each time point. The asterisk indicates a significant difference versus the corresponding control value measured before the induction of SAH.
| |
View larger version (16K):
[in a new window]
|
Fig 4. Graph shows the relationship between changes in the diameter of the basilar artery versus the concentration (conc.) of 20-HETE in CSF at various time points after induction of the dual hemorrhage model of SAH in dogs.
| |
View larger version (10K):
[in a new window]
|
Fig 5. Graph shows the effects of acute administration of TS-011 (1 mg/kg IV) on the diameter of the basilar artery of dogs, with documented evidence of delayed vasospasm after induction of the dual hemorrhage model of SAH. Paired angiograms were obtained in 9 dogs before and 1 hour after administration of TS-011. The asterisk indicates a significant difference in the diameter of the basilar artery versus that of the corresponding control value measured before administration of TS-011.
| |
View larger version (135K):
[in a new window]
|
Fig 6. Representative sequential angiograms obtained in a dog after induction of the dual hemorrhage model of subarachnoid hemorrhage that was chronically treated with TS-011 (1 mg/kg twice a day) from initiation of SAH. The left panel presents the control angiogram before induction of SAH. The middle panel depicts the diameter of the basilar artery 3 days after the first cisternal injection of blood. The right panel depicts the appearance of the basilar artery 3 days after the second cisternal injection of blood. The arrow indicates the narrowest point in the basilar artery, which is showing vasospasm where sequential measurements were made.
| |
