Effects of Postconditioning on Neurogenesis and Angiogenesis During the Recovery Phase After Focal Cerebral Ischemia
Ischemic postconditioning has been shown in experimental stroke models to be a viable and exciting option for ischemic neuroprotection. Specifically, postconditioning in the acute phase of experimental ischemic stroke may reduce infarct size by altering mechanisms of cell death. The current proof-of-concept study assessed if comparable positive results could be seen in the delayed phase of ischemic neuronal injury. The authors further sought to evaluate if amplification of neurogenesis and angiogenesis could be mechanistically implicated in the positive effects of ischemic postconditioning in the delayed phase of ischemic stroke. In a male rat model of middle cerebral artery occlusion ischemic stroke, 9 rats received ischemic postconditioning, and 8 rats received poststroke standard care. After 14 days of recovery, rats subjected to ischemic postconditioning had significantly smaller infarct volumes, and exhibited significantly better stroke scores when compared with controls. These favorable results correlated with an increase in markers of neurogenesis (doublecortin/BrdU) in the ipsilateral hemisphere; and an increased density of collagen-IV/Ki67 positive cells in the peri-infarct microvessels, suggestive of enhanced vascular remodeling. These data suggest that the beneficial effects of ischemic postconditioning could be sustained for ≤2 weeks, and offer potential mechanistic insights into this promising technique of neuroprotection. The study was limited by the use of a single protocol for postischemic conditioning with fixed dose and timing, evaluation of limited cell types, and short outcome assessment. It will be interesting to see if these results will be translated into future human studies of ischemic neuroprotection and stroke recovery. See p 2691.
Residual Risk of Stroke and Death in Anticoagulated Patients According to the Type of Atrial Fibrillation: AMADEUS Trial
There is clinical uncertainty about the potential differential risk of embolic stroke in permanent atrial fibrillation (AF) when compared with nonpermanent AF. Multiple studies have shown conflicting results in that regard, and little is known about outcomes in anticoagulated patients in these subgroups. Although it is known that the association of heart failure (HF) and AF increases the risk of death, it is not clear if HF can differentially affect cardiovascular outcomes according to the permanency of AF. The authors of this article sought to answer these questions by performing a retrospective analysis of data from the AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation) trial, a randomized controlled trial of fixed-dose idraparinux versus dose-adjusted vitamin K antagonist in patients with nonvalvular AF. A total of 4556 patients had AF, of which 54% had permanent AF. Patients with permanent AF had a significantly higher burden of HF when compared with patients with nonpermanent AF (29% versus 16%; P<0.001). The primary outcome, a composite of cardiovascular death, stroke or systemic embolism, was more frequent in patients with permanent AF when compared with patients with nonpermanent AF (hazard ratio, 1.66; 95% confidence interval, 1.08–2.55, for multivariate analysis). There was no apparent association with type of anticoagulation regimen. In addition, there was no interaction between the presence of HF and the permanency of AF. This suggests that HF increased the risk of adverse outcomes after anticoagulation similarly in permanent and nonpermanent AF. Thus, this hypothesis-generating study indicates that patients with permanent AF are at higher risk of significant cardiovascular morbidity and death than patients with nonpermanent AF, even when anticoagulated. The authors note that their study population was at relatively lower risk of both ischemic and hemorrhagic events than the general population. Regardless, the study highlights that permanent AF may be more ominous than thought. This calls for improved therapeutic strategies to manage patients with permanent AF, other than anticoagulation alone. See p 2523.
Low-Versus Standard-Dose Alteplase for Ischemic Strokes Within 4.5 Hours: A Comparative Effectiveness and Safety Study
In Asia, low-dose intravenous alteplase (0.6 mg/kg) has been used for acute ischemic stroke thrombolysis in a high proportion of cases. This alternate dosage has been applied given concern for increased risk of intracranial hemorrhage in Asians when compared with Westerners. The efficacy of such as strategy is unknown, and there are no available clinical trial data comparing standard dose alteplase to its low-dose alternative. The authors of this study sought to determine if low-dose alteplase is safe and effective for acute ischemic stroke thrombolysis. They analyzed data from a prospective, multicenter, nationwide acute stroke registry database in South Korea. From the 15 815 acute ischemic stroke cases, a subset of 1526 patients with neuroimaging-confirmed ischemic stroke and who received intravenous alteplase within 4.5 hours were studied. The mean National Institutes of Health Stroke Scale (NIHSS) score was 11.5±6.5 points, 29.5% received low-dose alteplase, and 26.5% underwent endovascular recanalization. The efficacy of low-dose alteplase when compared with standard-dose alteplase was equivalent for favorable 3-month modified Rankin Scale score of 0 to 1 (adjusted odds ratio, 0.95; 95% confidence interval, 0.68–1.32) and symptomatic hemorrhagic transformation (1.05; 0.65–1.70). Of interest, 3-month mortality was improved in the low-dose group (0.54; 0.35–0.83). These findings persisted even after exclusion of patients who received thrombectomy. These interesting results prompt consideration of an alternative dosage of intravenous alteplase for acute stroke thrombolysis in patients who are at high risk of systemic hemorrhage. The reasons leading to lower mortality rates in this registry are not clear. Given the inherent limitations of this and other registry analyses, a multinational randomized clinical trial comparing low-dose versus standard-dose alteplase is currently ongoing, the results of which are much awaited. See p 2541.
- © 2015 American Heart Association, Inc.
- Effects of Postconditioning on Neurogenesis and Angiogenesis During the Recovery Phase After Focal Cerebral Ischemia
- Residual Risk of Stroke and Death in Anticoagulated Patients According to the Type of Atrial Fibrillation: AMADEUS Trial
- Low-Versus Standard-Dose Alteplase for Ischemic Strokes Within 4.5 Hours: A Comparative Effectiveness and Safety Study
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