Comprehensive Management of Stroke: From Mechanisms to Therapeutic Approaches.

Acute ischemic stroke (AIS) is a challenging disease, which needs urgent comprehensive management. Endovascular thrombectomy (EVT), alone or combined with iv thrombolysis, is currently the most effective therapy for patients with acute ischemic stroke (AIS). However, only a limited number of patients are eligible for this time-sensitive treatment. Even though there is still significant room for improvement in the management of this group of patients, up until now there have been no alternative therapies approved for use in clinical practice. However, there is still hope, as clinical research with novel emerging therapies is now generating promising results. These drugs happen to stop or palliate some of the underlying molecular mechanisms involved in cerebral ischemia and secondary brain damage. The aim of this review is to provide a deep understanding of these mechanisms and the pathogenesis of AIS. Later, we will discuss the potential therapies that have already demonstrated, in preclinical or clinical studies, to improve the outcomes of patients with AIS.

Maintenance over Time of the Effect Produced by Esmolol on the Structure and Function of Coronary Arteries in Hypertensive Heart Diseases.

We previously observed that esmolol treatment for 48 h reduced vascular lesions in spontaneously hypertensive rats (SHRs). Therefore, we investigated whether this beneficial effect is persistent after withdrawal. Fourteen-month-old SHRs (SHR-Es) were treated with esmolol (300 µg/kg/min) or a vehicle for 48 h. Two separate groups were also given identical treatment, but they were then monitored for a further 1 week and 1 month after drug withdrawal. We analyzed the geometry and composition of the coronary artery, vascular reactivity and plasma redox status. Esmolol significantly decreased wall thickness (medial layer thickness and cell count), external diameter and cross-sectional area of the artery, and this effect persisted 1 month after drug withdrawal. Esmolol significantly improved endothelium-dependent relaxation by ACh (10-9-10-4 mol/L); this effect persisted 1 week (10-9-10-4 mol/L) and 1 month (10-6-10-4 mol/L) after withdrawal. Esmolol reduced the contraction induced by 5-HT (3 × 10-8-3 × 10-5 mol/L), and this effect persisted 1 week after withdrawal (10-6-3 × 10-5 mol/L). Esmolol increased nitrates and reduced glutathione, and it decreased malondialdehyde and carbonyls; this enhancement was maintained 1 month after withdrawal. This study shows that the effect of esmolol on coronary remodeling is persistent after treatment withdrawal in SHRs, and the improvement in plasma oxidative status can be implicated in this effect.

Reanimación cardiopulmonar en prono a propósito de un caso / Case report cardiopulmonary resuscitation in prone position

Prone position is necessary for some neurosurgical and othopedic procedures. Cardiopulmonary resuscitation (CPR) in prone position was first described by McNeil in 1989, since then several successful cases have been published. We report the case of a 72-year-old patient with history of stage IV breast cancer who presented acute spinal cord compression due to a vertebral fracture at T10 level. Surgical spinal cord decompression and posterior arthrodesis was performed. After three hours of surgery, cardiorespiratory arrest occur while patient was in prone position. Unestable spine and fixed head made turning the patient into supine position very difficult, consequently prone CPR manoeuvres were started with recovery of spontaneous circulation. In case of cardiorespiratory arrest in prone position, the intense fixation and the extent of the surgical incision make the change to supine a time-consuming and technically complex procedure. If cardiorespiratory arrest occurs in the prone position, CPR in the prone position might be reasonable.

La posición de decúbito prono es necesaria para la realización de algunos procedimientos neuroquirúrgicos y traumatológicos. La reanimación cardiopulmonar (RCP) en prono fue descrita por primera vez por McNeil en 1989, desde entonces se han publicado varios casos de RCP en prono con buen resultado. Presentamos el caso de una paciente de 72 años con antecedentes de carcinoma de mama estadio IV que presenta síndrome de compresión medular por fractura patológica a nivel de T10. Se decide realizar descompresión medular y artrodesis por vía posterior. A las 3 horas de la cirugía se produjo parada cardiorrespiratoria en prono. Dada la inestabilidad espinal y la fijación de la paciente, el cambio a supino era complejo por lo que se iniciaron maniobras de RCP en prono con posterior recuperación de circulación espontánea. En caso de parda cardiorrespiratoria en prono, la intensa fijación y la extensión de la incisión quirúrgica hace que el cambio a supino consuma tiempo y sea técnicamente complejo. Si la PCR ocurre en prono, está justificado iniciar las maniobras de RCP en esta posición.

Early regression of coronary artery remodeling with esmolol and DDAH/ADMA pathway in hypertensive rats.

Our preclinical study demonstrated that esmolol produces early regression of left ventricular hypertrophy in arterial hypertension. The aim of this study was to assess the effects of short-term esmolol therapy on the regression of left anterior descending artery remodeling in spontaneously hypertensive rats (SHRs), and to determine whether the asymmetric dimethylarginine (ADMA)/dimethylarginine dimethylaminohydrolase (DDAH) pathway, a regulator of nitric oxide (NO) bioavailability, accounted for this regression. Fourteen-month-old male SHRs were treated intravenously with vehicle (SHR, n=15) or esmolol (SHR-E, n=20) (300 µg kg-1 min-1). Age-matched, vehicle-treated male Wistar-Kyoto rats (WKY, n=15) served as controls. SHRs were also treated with nitroglycerin (SHR-N, n=5). After 48 h, the left anterior descending artery structure and morphology were assessed, and dose-response curves for 5-hydroxytryptamine (5-HT, 10-9-3 × 10-5 mol l-1) were constructed. ADMA concentrations in plasma and left ventricle and DDAH activity in tissue were analyzed. Wall thickness and cross-sectional area were significantly lower after treatment with esmolol in SHR-E than in SHR. Media thickness and smooth muscle cell count were lower in SHR-E than in SHR. Esmolol induced a significant reduction in adventitial cell count in SHR-E. The area under the concentration-response curves was significantly higher in SHR than in SHR-E, as were the esmolol normalized coronary artery contracting responses to 5-HT. We found significantly lower ADMA levels and significantly higher DDAH activity in the ventricle in SHR-E than in SHR. The protective effect of esmolol on the regression of left anterior descending artery remodeling may be related to the reduction in ADMA levels.

Short-term esmolol improves coronary artery remodeling in spontaneously hypertensive rats through increased nitric oxide bioavailability and superoxide dismutase activity.

The aim of this study was to assess the effects of short-term esmolol therapy on coronary artery structure and function and plasma oxidative stress in spontaneously hypertensive rats (SHR). For this purpose, 14-month-old male SHR were treated for 48 hours with esmolol (SHR-E, 300 µ g/kg/min). Age-matched untreated male SHR and Wistar Kyoto rats (WKY) were used as hypertensive and normotensive controls, respectively. At the end of intervention we performed a histological study to analyze coronary artery wall width (WW), wall-to-lumen ratio (W/L), and media cross-sectional area (MCSA). Dose-response curves for acetylcholine (ACh) and sodium nitroprusside were constructed. We also assessed several plasma oxidative stress biomarkers, namely, superoxide scavenging activity (SOSA), nitrites, and total antioxidant capacity (TAC). We observed a significant reduction in WW (P < 0.001), W/L (P < 0.05), and MCSA (P < 0.01) and improved endothelium-dependent relaxation (AUC(SHR-E) = 201.2 ± 33 versus AUC(SHR) = 97.5 ± 21, P < 0.05) in SHR-E compared with untreated SHR; no differences were observed for WW, MCSA, and endothelium-dependent relaxation by ACh at higher concentrations (10(-6) to 10(-4) mol/l) for SHR-E with respect to WKY. SOSA (P < 0.001) and nitrite (P < 0.01) values were significantly higher in SHR-E than in untreated SHR; however, TAC did not increase after treatment with esmolol. Esmolol improves early coronary artery remodeling in SHR.