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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003ESubarachnoid hemorrhages that result from ruptured aneurysms initiate a series of events that may result in very poor outcomes. This article give an overview of the biological mechanisms of vasospasms that result from ruptured aneurysm blood clots.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Eischemia\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Einterventional techniques \u0026amp; devices\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003ESubarachnoid hemorrhages that result from ruptured aneurysms initiate a series of events that may result in very poor outcomes. R. Loch MacDonald, MD, University of Toronto, Toronto, Ontario, Canada, gave an overview of the biological mechanisms of vasospasms that result from ruptured aneurysm blood clots. \u201cThe erythrocyte seems to be the component of the blood that is primarily responsible for initiating the delayed angiographic response that occurs,\u201d said Dr. MacDonald. The vasospasms are related to smooth muscle contraction, possibly due to increases in endothelin or prostaglandins, decreases in the relaxant nitric oxide, neurotransmitters, membrane depolarization, increased sensitivity to calcium, or impairment of muscle relaxation pathways. Barth et al (\u003Cem\u003EStroke\u003C\/em\u003E 2007) conducted a study of the calcium channel blocker nicardipine in 32 patients undergoing craniotomy for aneurysm. Nicardipine pellets (40 mg) were placed in the basal cisterns of 16 patients. On Day 8, the incidence of vasospasms in the nicardipine-treated patients was reduced from 73% to 7% (p\u0026lt;0.05) and mortality between treated (6%) and placebo patients (38%) reached statistical significance (p=0.042). \u201cThis fits with the depolarization mechanism of vasospasm,\u201d noted Dr. MacDonald. In preclinical models, endothelin antagonists are successful in preventing vasospasm. This was confirmed in the phase 2 CONSCIOUS-1 study. Three doses of clazosentan were used to treat patients with subarachnoid hemorrhage, and all 3 doses were significantly better than placebo in preventing vasospasm (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). In addition to the effects of the blood clot, secondary processes such as disturbance of the blood brain barrier, hypertension, brain edema, apoptosis, and global ischemia are at play. \u201cIt starts to become even more complicated when you add in these other mechanisms\u2026all can contribute to ischemia, infarction, and poor outcome,\u201d said Dr. MacDonald.\u003C\/p\u003E\n         \u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/1\/26\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Clazosentan Prevents Cerebral Vasospasm.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-401249483\u0022 data-figure-caption=\u0022Clazosentan Prevents Cerebral Vasospasm.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/1\/26\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/1\/26\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/1\/26\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/11001\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-3\u0022 class=\u0022first-child\u0022\u003EClazosentan Prevents Cerebral Vasospasm.\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EGiven the serious consequences of vasospasm, researchers have proposed performing angioplasty as prophylactic treatment. Richard Latchaw, MD, University of California, Davis, CA, presented work from Jonathan Hartman, MD, Kaiser Permanente Sacramento Medical Center, Sacramento, CA, that explored this approach. \u201cThis is a dangerous procedure\u2026every time I do angioplasty on a post-subarachnoid hemorrhage patient, I really respect those vessels because they are very tender vessels. It\u0027s very easy to produce overdilitation and rupture,\u201d cautioned Dr. Latchaw. The Balloon Prophylaxis of Aneurysmal Vasospasm (BPAV) study was a phase 2 trial that was conducted to determine if prophylactic angioplasty performed within 96 hours of a Fisher grade III or III+IV subarachnoid hemorrhage would alleviate vasospasm. The study enrolled 170 patients and was conducted at 10 centers in the US, Canada, and the Netherlands. Based on 3 deaths that occurred during the study, the protocol was modified to exclude A1 and P1 segments, as it was believed that these were too dangerous. A total of 81 patients received prophylactic angioplasty, with 1 perforation and 3 deaths. There was no statistically significant difference between the group that received balloon angioplasty and the control group in terms of vasospasm, outcomes at 3 months, length of hospital stay, or the probability of delayed ischemic neurological deficits. \u201cOne of the confounding factors is that the ballooned patients tended to have a higher degree of hydrocephalus, which may have made that group look a little worse,\u201d noted Dr. Latchaw. However, the need for therapeutic balloon angioplasty was significantly higher in the control group (p=0.03). \u201cThis is the most significant part of this study,\u201d concluded Dr. Latchaw.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2008 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/8\/1\/26.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzmhn2\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzmhn2\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}