Ebook Cerebral vasospasm - Advances in research and treatment: Part 2
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Ebook Cerebral vasospasm - Advances in research and treatment: Part 2
SECTION VExperimental Treatments36Prevention of Experimental Cerebral Vasospasm by Intrathecal Delivery of Liposomal FasudilYOSHIHIRO TAKANASHI, M.D., Ebook Cerebral vasospasm - Advances in research and treatment: Part 2, PH.D., TATSUHIRO ISHIDA, PH.D., JOHN H. ZHANG, M.D., PH.D., ISAO YAMAMOTO, M.D.AbstractWe investigated the safety and efficacy of a sustained release form of liposomal fasudil for the prevention of cerebral vasospasm after experimental subarachnoid hemorrhage (SAH) in rats and dogs. The safety of Ebook Cerebral vasospasm - Advances in research and treatment: Part 2a large intrathecal dose of liposomal fasudil was tested in IS rars. Rats were divided into one of three groups. Each group received either 2.5 mg kgEbook Cerebral vasospasm - Advances in research and treatment: Part 2
or 5 mg kg of liposomal fasudil or drug-free liposomes after SAH. Next, experimental SAH was induced in 15 dogs by injection of autologous arterial blSECTION VExperimental Treatments36Prevention of Experimental Cerebral Vasospasm by Intrathecal Delivery of Liposomal FasudilYOSHIHIRO TAKANASHI, M.D., Ebook Cerebral vasospasm - Advances in research and treatment: Part 2erna magna (treatment group). In four animals, drug-free liposomes were similarly injected (placebo group), and the remaining five animals were treated with no liposomal injection after SAH (control group). On day 7 after SAH. angiography was repeated and cerebrospinal fluid was collected before sac Ebook Cerebral vasospasm - Advances in research and treatment: Part 2rifice. In the safety study in rats, histological examination of the brains revealed no abnormalities. In the placebo and control groups, significantEbook Cerebral vasospasm - Advances in research and treatment: Part 2
vasospasm occurred in the canine basilar artery' on day 7. In the treatment group, vasospasm on basilar artery was significantly ameliorated (p < .01)SECTION VExperimental Treatments36Prevention of Experimental Cerebral Vasospasm by Intrathecal Delivery of Liposomal FasudilYOSHIHIRO TAKANASHI, M.D., Ebook Cerebral vasospasm - Advances in research and treatment: Part 2and effective strategy for preventing vasospasm on experimental SAH.Intrathecal drug therapy for cerebral vasospasm following subarachnoid hemorrhage (SAH) has some advantages over systemic delivery and may be more efficacious than systemic application.1-3 In the current study, we have devised a sus Ebook Cerebral vasospasm - Advances in research and treatment: Part 2tained-release form of fasudil (liposomal fasudil) that can be used intrathe-cally and can continuously release the drug for several days. We investigEbook Cerebral vasospasm - Advances in research and treatment: Part 2
ated the safety and efficacy of liposomal fasudil in a sustained-release form for the prevention of cerebral vasospasm after experimental SAH.MaterialSECTION VExperimental Treatments36Prevention of Experimental Cerebral Vasospasm by Intrathecal Delivery of Liposomal FasudilYOSHIHIRO TAKANASHI, M.D., Ebook Cerebral vasospasm - Advances in research and treatment: Part 2ded into one of tlưee experimental groups. Experimental SAH was produced in all rats by two injections of autologous blood into the cisterna magna.- Two hours after the second blood injection the animals received either 2.5 mg kg of liposomal153IMSECTION V ■ EXPERIMENTAL TREATMENTSfasudil (M = 6). 5 Ebook Cerebral vasospasm - Advances in research and treatment: Part 2 mg'kg of liposomal fasudil (n = 6). or drug-free liposomes (n = 6) injected into the cisterna magna. Seven days after the initial blood injection, thEbook Cerebral vasospasm - Advances in research and treatment: Part 2
e brains were removed for histological examination.Canine SAH ModelExperimental SAH was induced in 15 dogs by injection of autologous arterial blood iSECTION VExperimental Treatments36Prevention of Experimental Cerebral Vasospasm by Intrathecal Delivery of Liposomal FasudilYOSHIHIRO TAKANASHI, M.D., Ebook Cerebral vasospasm - Advances in research and treatment: Part 2imals. 0.94 mg kg of liposomal fasudil was injected into the cisterna magna (treatment group). In four animals, drug-free liposomes were similarly injected (placebo group), and the remaining five animals were treated with no liposomal injection after SAH (control group). On day 7 angiography was rep Ebook Cerebral vasospasm - Advances in research and treatment: Part 2eated, and cerebrospinal fluid was collected before sacrifice. The percent change in basilar artery diameter was calculated by dividing the diameter oEbook Cerebral vasospasm - Advances in research and treatment: Part 2
f the basilar artery observed on the angiogram 7 days after SAH by that of the control diameter obtained from the baseline angiogram.ResultsRelease ofSECTION VExperimental Treatments36Prevention of Experimental Cerebral Vasospasm by Intrathecal Delivery of Liposomal FasudilYOSHIHIRO TAKANASHI, M.D., Ebook Cerebral vasospasm - Advances in research and treatment: Part 2, 69% of the fasudil was released from liposomes incubated in control cerebrospinal fluid. As expected, no fasudil was detectable in blood samples.Safety StudyOn gross examination the brain, vessels, and meninges of all rats appeared normal. Light microscopy of thebrain parenchyma, ependyma, vessels Ebook Cerebral vasospasm - Advances in research and treatment: Part 2, and basal meninges appeared histologically normal.Changes 111 Basilar Artery DiametersLiposomal fasudil. at the nontoxic dose of 0.94 mg.'kg. signifEbook Cerebral vasospasm - Advances in research and treatment: Part 2
icantly prevented vasoconstriction in the canine basilar artery when compared with that of the control group and the placebo group (Fig. 36-1).DiscussSECTION VExperimental Treatments36Prevention of Experimental Cerebral Vasospasm by Intrathecal Delivery of Liposomal FasudilYOSHIHIRO TAKANASHI, M.D., Ebook Cerebral vasospasm - Advances in research and treatment: Part 2temic administration in many cases, the intrathecal route has drawbacks to adaptation for clinical use. The time during which drug concentrations remain in the therapeutic window may be short even with intrathecal delivery. Additional difficulties are the technical problems associated with intrathec Ebook Cerebral vasospasm - Advances in research and treatment: Part 2al administration (complications associated with the prolonged presence of external catheters), risk of infection and bleeding, potential adverse effeEbook Cerebral vasospasm - Advances in research and treatment: Part 2
cts on intracranial pressure, and the theoretical concern that drug distribution may be adversely affected in the patient with SAH. Therefore, with reSECTION VExperimental Treatments36Prevention of Experimental Cerebral Vasospasm by Intrathecal Delivery of Liposomal FasudilYOSHIHIRO TAKANASHI, M.D., Ebook Cerebral vasospasm - Advances in research and treatment: Part 2, the use of which is hampered clinically by the factors already cited.To overcome some of these disadvantages, various methods of sustained local drug delivery have been introduced for the treatment of experimental vasospasm. Inoue et al showed that intrathecal implantation of a slow-release tablet Ebook Cerebral vasospasm - Advances in research and treatment: Part 2 containing calcitonin gene-related peptide prevents vasospasm following SAH in monkeys? Shiokawa and colleagues used a prolonged-release pellet of paEbook Cerebral vasospasm - Advances in research and treatment: Part 2
paverine that could be implanted intracranially at the time of surgery andFIGLRE 36-1 The diameter of the dog basilar artery 7 days after subarachnoidSECTION VExperimental Treatments36Prevention of Experimental Cerebral Vasospasm by Intrathecal Delivery of Liposomal FasudilYOSHIHIRO TAKANASHI, M.D., Ebook Cerebral vasospasm - Advances in research and treatment: Part 2atment with liposomal fasudil significantly reduced the narrowing of the basila? artery oil day 7 (* p < .01 vs drug-free group and control group).CHAPTER 36• 1NTRAT1reported that this prevented vasospasm ill dogs.’ Both methods require craniotomy to implant intracranially because the drug was conta Ebook Cerebral vasospasm - Advances in research and treatment: Part 2ined in a solid form On the contrary, liposomal fasudil that was used in this study is a liquid that can be delivered intracranially at the time of suEbook Cerebral vasospasm - Advances in research and treatment: Part 2
rgery or at other times by lumbar puncture. This might have the advantage of diffuse distribution of the drug throughout the entire neuraxis.An additiSECTION VExperimental Treatments36Prevention of Experimental Cerebral Vasospasm by Intrathecal Delivery of Liposomal FasudilYOSHIHIRO TAKANASHI, M.D., Ebook Cerebral vasospasm - Advances in research and treatment: Part 2 the advantage that a single intrathecal injection of liposomal fasudil might achieve a therapeutic drug concentration in the cerebrospinal fluid and prevent cerebral vasospasm, thus avoiding the need for frequent or continuous drug infusion. The results obtained from the current study may be an int Ebook Cerebral vasospasm - Advances in research and treatment: Part 2riguing first step in applying the concept of sustained local drug delivery to the treatment of cerebral vasospasm in the clinical setting.REFERENCES1Ebook Cerebral vasospasm - Advances in research and treatment: Part 2
Takanastu Y. Ishida T. Kirchmeier MJ. Shuaib A. Allen TM Neuroprotection by intrathecal application of liposome-entrapped fasudil in a rat model of isSECTION VExperimental Treatments36Prevention of Experimental Cerebral Vasospasm by Intrathecal Delivery of Liposomal FasudilYOSHIHIRO TAKANASHI, M.D.,SECTION VExperimental Treatments36Prevention of Experimental Cerebral Vasospasm by Intrathecal Delivery of Liposomal FasudilYOSHIHIRO TAKANASHI, M.D.,Gọi ngay
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