cardiovascular-agents and Ischemic-Stroke

Collateral circulation plays a vital role in sustaining blood flow to the ischaemic areas in acute, subacute or chronic phases after an ischaemic stroke or transient ischaemic attack. Good collateral circulation has shown protective effects towards a favourable functional outcome and a lower risk of recurrence in stroke attributed to different aetiologies or undergoing medical or endovascular treatment. Over the past decade, the importance of collateral circulation has attracted more attention and is becoming a hot spot for research. However, the diversity in imaging methods and criteria to evaluate collateral circulation has hindered comparisons of findings from different cohorts and further studies in exploring the clinical relevance of collateral circulation and possible methods to enhance collateral flow. The statement is aimed to update currently available evidence and provide evidence-based recommendations regarding grading methods for collateral circulation, its significance in patients with stroke and methods under investigation to improve collateral flow.

Topics: Cardiovascular Agents; Cerebral Revascularization; Cerebrovascular Circulation; Collateral Circulation; Consensus; Endovascular Procedures; Evidence-Based Medicine; Humans; Ischemic Stroke; Thrombolytic Therapy; Treatment Outcome

Adrenomedullin (AM), a vasoactive peptide, has strong anti-inflammatory and angiogenic properties, which have been reported to ameliorate the consequences of ischemic stroke in several animal models. After a phase I study in healthy volunteers, two phase II trials of AM for inflammatory bowel diseases have been recently completed. The current AdrenoMedullin For Ischemic Stroke (AMFIS) study aims to assess the safety and efficacy of AM in patients with acute ischemic stroke.. The AMFIS study is an investigator-initiated, randomized, double-blind, phase-II trial. AM or placebo will be administered to patients with non-cardioembolic ischemic stroke within 24 h after stroke onset. In the first cohort of the AMFIS study, patients will be randomly allocated to the investigation treatment A (30 μg/kg of AM in total for 7 days, n = 20) or placebo group (n = 10). In the second cohort, patients will be assigned to the investigation treatment B (56 μg/kg of AM in total for 7 days, n = 20) or placebo group (n = 10).. Serious adverse events related to the protocol treatment will be evaluated as the primary outcome. All adverse events will be analyzed as the secondary outcome. Regarding efficacy endpoints, the change in National Institutes of Health Stroke Scale and modified Rankin Scale scores will be compared between investigation treatment and placebo groups.. AM is expected to be a safe and effective treatment for ischemic stroke.

Topics: Adrenomedullin; Adult; Aged; Aged, 80 and over; Cardiovascular Agents; Clinical Trials, Phase II as Topic; Double-Blind Method; Female; Humans; Ischemic Stroke; Japan; Male; Middle Aged; Randomized Controlled Trials as Topic; Treatment Outcome; Young Adult

A sensitive and robust method has been developed using an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay to quantify Tat-K13, a novel interfering peptide for the treatment of ischemic stroke, in human plasma. Automated solid-phase extraction on a Waters Oasis WCX (30 μm, 10 mg) 96-well plate was used to extract Tat-K13 from human plasma and the extracts were separated on a Waters Acquity CSH column (2.1 × 50 mm i.d., 1.7 μm) with a gradient elution method by mobile phase A (nonafluoropentanoic acid-acetic acid-water, 1:2:1000, v/v/v) and B (nonafluoropentanoic acid-acetic acid-water-acetonitrile, 1:2:100:900, v/v/v/v). The method was fully validated following international bioanalytical guidelines and showed good linearity from 2.10 to 1,050 ng/ml. The method was successfully applied to investigate the clinical pharmacokinetics of Tat-K13 in health volunteers. Rapid elimination of Tat-K13 from the body was observed, with half-life ranging from 0.26 to 0.78 h across different dose levels. The exposure of Tat-K13 was approximately dose-dependent in terms of the area under the concentration-time curve and peak concentration.

Topics: Adolescent; Adult; Cardiovascular Agents; Chromatography, High Pressure Liquid; Humans; Ischemic Stroke; Middle Aged; Peptides; Reproducibility of Results; Tandem Mass Spectrometry; Young Adult