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Determinants of the impact of blood pressure variability on neurological outcome after acute ischaemic stroke

Stroke & Vascular Neurology 2017年第1期2卷 1-6页

作者： Adam de Havenon Alicia Bennett Gregory J Stoddard Gordon Smith Lee Chung Steve O’Donnell J Scott McNally David Tirschwell jennifer J Majersik Department of Neurology University of UtahSaltLake CityUtahUSA University of Utah SaltLake CityUtahUSA University of Washington SeattleWashingtonUSA

Introduction: Increased blood pressure variability (BPV) is detrimental after acute ischaemic stroke, but the interaction between BPV and neuroimaging factors that directly influence stroke outcome has not been explored. Methods: We retrospectively reviewed inpatients from 2007 to 2014 with acute anterior circulation ischaemic stroke, CT perfusion and angiography at hospital admission, and a modified Rankin Scale (MRS) 30- 365 days after stroke onset. BPV indices included SD, coefficient of variation and successive variation of the systolic blood pressure between 0 and 120 hours after admission. Ordinal logistic regression models were fitted to MRS with predictor variables of BPV indices. Models were further stratified by CT perfusion volumetric measurements, proximal vessel occlusion and collateral score. Results: 110 patients met the inclusion criteria. The likelihood of a 1-point rise in the MRS increased with every 10 mm Hg increase in BPV (OR for the 3 BPV indices ranged from 2.27 to 5.54), which was more pronounced in patients with larger ischaemic core volumes (OR 8.37 to 18.0) and larger hypoperfused volumes (OR 6.02 to 15.4). This association also held true for patients with larger mismatch volume, proximal vessel occlusion and good collateral vessels. Conclusions: These results indicate that increased BPV is associated with worse neurological outcome after stroke, particularly in patients with a large lesion core volume, concurrent viable ischaemic penumbra, proximal vessel occlusion and good collaterals. This subset of patients, who are often not candidates for or fail acute stroke therapies such as intravenous tissue plasminogen activator or endovascular thrombectomy, may benefit from interventions aimed at reducing BPV.

关键词： impaired perfusion cerebral

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Competitive metabolism of L-arginine:arginase as a therapeutic target in asthma

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The Journal of Biomedical Research 2011年第5期25卷 299-308页

作者： jennifer M.Bratt Amir A.Zeki Jerold A.Last Nicholas J.Kenyon Department of Internal Medicine Division of Pulmonary and Critical Care and Sleep MedicineUniversity of California

Exhaled breath nitric oxide （NO） is an accepted asthma biomarker. Lung concentrations of NO and its amino acid precursor, L-arginine, are regulated by the relative expressions of the NO synthase （NOS） and arginase isoforms. Increased expression of arginase I and NOS2 occurs in murine models of allergic asthma and in biopsies of asthmatic airways. Although clinical trials involving the inhibition of NO-producing enzymes have shown mixed results, small molecule arginase inhibitors have shown potential as a therapeutic intervention in animal and cell culture models. Their transition to clinical trials is hampered by concerns regarding their safety and potential tox- icity. In this review, we discuss the paradigm of arginase and NOS competition for their substrate L-arginine in the asthmatic airway. We address the functional role of L-arginine in inflammation and the potential role of arginase inhibitors as therapeutics.

关键词： nitric oxide L-arginine arginase nor-NOHA nitrosation nitric oxide synthase

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