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Adrenomedullin in Patients With Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage

2000; Lippincott Williams & Wilkins; Volume: 31; Issue: 12 Linguagem: Inglês

10.1161/01.str.31.12.3079-d

1524-4628

Masayuki Fujioka, Kenji Nishio, Toshisuke Sakaki, Naoto Minamino, Kazuo Kitamura,

Anesthesia and Pain Management

HomeStrokeVol. 31, No. 12Adrenomedullin in Patients With Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage Free AccessOtherPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessOtherPDF/EPUBAdrenomedullin in Patients With Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage Masayuki Fujioka Kenji Nishio Toshisuke Sakaki Naoto Minamino Kazuo Kitamura Masayuki FujiokaMasayuki Fujioka Department of Neurosurgery, Emergency and Critical Care Medical Center, Nara Prefectual Nara Hospital Kenji NishioKenji Nishio Department of Emergency and Critical Care Medicine, Nara Medical University Toshisuke SakakiToshisuke Sakaki Department of Neurosurgery, Nara Medical University, Nara, Japan Naoto MinaminoNaoto Minamino National Cardiovascular Center Research Institute, Osaka, Japan Kazuo KitamuraKazuo Kitamura First Department of Internal Medicine, Miyazaki Medical College, Miyazaki, Japan Originally published1 Dec 2000https://doi.org/10.1161/01.STR.31.12.3079-dStroke. 2000;31:3079–3083To the Editor: Cerebral vasospasm leading to delayed brain ischemia is a major cause of death in patients who initially survive subarachnoid hemorrhage (SAH).12 Because of this, the prediction and treatment of vasospasm are critical in the management of SAH patients. Recent studies published in Stroke have reported that several factors, including age <50 years,3 hyperglycemia,3 the duration of unconsciousness after SAH,4 and the plasma level of brain natriuretic peptide,5 could be predictors for the development of cerebral vasospasm after SAH. We suggest adrenomedullin as another possible marker of symptomatic vasospasm.In a human pheochromocytoma, we discovered adrenomedullin, which proved to be a vasorelaxant peptide of 52 amino acids.6 Adrenomedullin is a ubiquitous peptide that is also found in plasma and cerebrospinal fluid (CSF).7 The adrenomedullin gene is highly expressed in vascular endothelial and vascular smooth muscle cells.7 This peptide regulates the vascular tonus and growth of vascular cells as an autocrine and/or paracrine vasoactive hormone.67Several factors, such as endothelin, inflammatory cytokines, and oxygen free radicals, which seemingly play a role in vasospasm,289 stimulate the adrenomedullin production from vascular cells.710 Additionally, adrenomedullin in the central nervous system (CNS) is involved in controlling brain function,7 and its mRNA and peptide are upregulated in the ischemic cerebral cortex of rodents.7 Therefore, if adrenomedullin plays a role in the pathological processes of cerebral vasospasm and subsequent brain ischemia in SAH patients, the CSF concentrations of adrenomedullin would be expected to change in relation to the vasospasm and brain ischemia.We investigated plasma and ventricular CSF concentrations of adrenomedullin by radioimmunoassay in 14 aneurysmal SAH patients (3 men and 11 women, mean age 62.0 [SD 7.3] years) in the early period (1 to 3 days after SAH, before vasospasm) and late period (7 to 9 days, development and progression of vasospasm). The 14 patients, who had no preexisting neurological diseases or other chronic disorders, underwent aneurysm clipping within 48 hours after admission. At the time of surgery, each patient had a Glasgow Coma Scale score11 exceeding 10. The plasma adrenomedullin concentration was also measured in 13 healthy control subjects (7 men and 6 women, mean age 32.2 [SD 6.6] years). Brain ischemia due to vasospasm was estimated by repeated neurological examinations and transcranial Doppler sonography and was confirmed by cerebral angiography and single-photon emission CT. We analyzed the adrenomedullin levels of plasma and CSF, comparing them to the presence of symptomatic vasospasm, with nonparametric statistical techniques.Plasma concentrations of adrenomedullin in the healthy controls averaged 5.05 [SEM 0.21] fmol/mL. In both early and late periods, the 4 patients with no vasospasm (NV) and the 10 patients with vasospasm (V) had significantly higher plasma concentrations of adrenomedullin than the healthy controls (in the NV group, P<0.001 for both periods; V group, P=0.001 and P<0.001 for early and late periods, respectively; Mann-Whitney U test). However, the plasma adrenomedullin concentration did not differ significantly between the 2 groups of NV and V in any period. In the NV and V groups, the plasma adrenomedullin levels did not change significantly over time.Unlike the plasma levels, the CSF adrenomedullin levels were significantly greater in the V group than in the NV group in the early and late periods (Table). Furthermore, only in the V group did the CSF concentration of adrenomedullin increase significantly in the late period compared with the early period (31.06 [SEM 7.52] and 11.02 [SEM 1.63], respectively; P=0.009). There was no statistically significant correlation between plasma and CSF adrenomedullin concentrations for the V group in the early or late periods.The patients with symptomatic vasospasm had significantly higher CSF levels of adrenomedullin than those without vasospasm from the prevasospasm period after SAH. In addition, the CSF adrenomedullin concentration increased with time in response to brain ischemia, and the increase was unrelated to the plasma concentrations. We speculate that the production sites of CSF adrenomedullin in these patients could be ischemic neurons,7 reactive astrocytes,7 infiltrating inflammatory cells in the ischemic brain,7 and/or cerebral vascular cells under oxidative stress.7 The CNS adrenomedullin may play a modulatory role in the cerebral vasospasm and subsequent brain ischemia after SAH. We suggest that CSF adrenomedullin can be a sensitive marker for symptomatic vasospasm. Table 1. Adrenomedullin Concentrations in Plasma and CSF in Patients With and Without Vasospasm After SAHNV Group (n=4)V Group (n=10)P*PlasmaDays 1–318.32 (1.16)15.01 (2.00)0.656Days 7–916.36 (1.45)16.65 (1.85)0.945CSFDays 1–32.55 (0.73)11.02 (1.63)0.011Days 7–94.59 (1.84)31.06 (7.52)†0.011Values are mean (SEM) fmol/mL.*Mann-Whitney U test; †significantly higher than days 1–3, P=0.009, Wilcoxon signed rank test. References 1 Kassell NF, Sasaki T, Colohan ART, Nazar G. Cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Stroke..1985; 16:562–572.CrossrefMedlineGoogle Scholar2 Macdonald RL, Weir BKA. A review of hemoglobin and the pathogenesis of cerebral vasospasm. Stroke..1991; 22:971–982.CrossrefMedlineGoogle Scholar3 Charpentier C, Audibert G, Guillemin F, Civit T, Ducrocq X, Bracard S, Hepner H, Picard L, Laxenaire MC. Multivariate analysis of predictors of cerebral vasospasm occurrence after aneurysmal subarachnoid hemorrhage. Stroke..1999; 30:1402–1408.CrossrefMedlineGoogle Scholar4 Hop JW, Rinkel GJE, Algra A, van Gijn J. Initial loss of consciousness and risk of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Stroke..1999; 30:2268–2271.CrossrefMedlineGoogle Scholar5 Sviri GE, Feinsod M, Soustiel JF. Brain natriuretic peptide and cerebral vasospasm in subarachnoid hemorrhage: clinical and TCD correlations. Stroke..2000; 31:118–122.CrossrefMedlineGoogle Scholar6 Kitamura K, Kangawa K, Kawamoto M, Ichiki Y, Nakamura S, Matsuo H, Eto T. Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. Biochem Biophys Res Commun..1993; 192:553–560.CrossrefMedlineGoogle Scholar7 Hinson JP, Kapas S, Smith DM. Adrenomedullin, a multifunctional regulatory peptide. Endocr Rev..2000; 21:138–167.MedlineGoogle Scholar8 Zubkov AY, Rollins S, Parent AD, Zhang J. Mechanism of endothelin-1-induced contraction in rabbit basilar artery. Stroke..2000; 31:526–533.CrossrefMedlineGoogle Scholar9 Osuka K, Suzuki Y, Watanabe Y, Takayasu M, Yoshida J. Inducible cyclooxygenase expression in canine basilar artery after experimental subarachnoid hemorrhage. Stroke..1998; 29:1219–1222.CrossrefMedlineGoogle Scholar10 Sugo S, Minamino N, Shoji H, Kangawa K, Matsuo H. Effects of vasoactive substances and cAMP related compounds on adrenomedullin production in cultured vascular smooth muscle cells. FEBS Lett..1995; 369:311–314.CrossrefMedlineGoogle Scholar11 Teasdale G, Jennett B. Assessment of coma and impaired consciousness: a practical scale. 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December 2000Vol 31, Issue 12Article InformationMetrics Copyright © 2000 by American Heart Associationhttps://doi.org/10.1161/01.STR.31.12.3079-d Originally publishedDecember 1, 2000 Keywordsvasospasmpeptidessubarachnoid hemorrhagePDF download Advertisement