Interactions between remote ischemic conditioning and post-stroke sleep regulation / 医学前沿

Sleep disturbances are common in patients with stroke, and sleep quality has a critical role in the onset and outcome of stroke. Poor sleep exacerbates neurological injury, impedes nerve regeneration, and elicits serious complications. Thus, exploring a therapy suitable for patients with stroke and sleep disturbances is imperative. As a multi-targeted nonpharmacological intervention, remote ischemic conditioning can reduce the ischemic size of the brain, improve the functional outcome of stroke, and increase sleep duration. Preclinical/clinical evidence showed that this method can inhibit the inflammatory response, mediate the signal transductions of adenosine, activate the efferents of the vagal nerve, and reset the circadian clocks, all of which are involved in sleep regulation. In particular, cytokines tumor necrosis factor α (TNFα) and adenosine are sleep factors, and electrical vagal nerve stimulation can improve insomnia. On the basis of the common mechanisms of remote ischemic conditioning and sleep regulation, a causal relationship was proposed between remote ischemic conditioning and post-stroke sleep quality.

Angioplastia primaria en el infarto agudo de miocardio: ¿es beneficioso el condicionamiento isquémico remoto?

El paradigma de la reapertura precoz de la arteria ocluida ha representado un hito en el tratamiento del infarto agudo de miocardio y su aplicación universal en la práctica cardiológica se tradujo en una reducción significativa de la magnitud del daño miocárdico y de la mortalidad por esta causa. Sin embargo, la oclusión coronaria aguda continúa siendo una causa prevalente de muerte y discapacidad de origen cardíaco, por lo cual persiste la búsqueda de nuevos procedimientos, fármacos o estrategias que contribuyan a una mayor preservación del tejido miocárdico en este contexto. El precondicionamiento isquémico cardíaco, en sus diferentes modalidades, a pesar de haber sido objeto de diversos estudios tanto a nivel clínico como experimental, no forma parte de la práctica habitual en los laboratorios de cateterismo cardíaco, servicios de cardiología crítica o unidades de emergencia móvil donde se lleva a cabo la reperfusión miocárdica. En esta controversia, los autores presentan argumentos a favor y en contra de la utilización del precondicionamiento isquémico remoto como adjunto a la angioplastia primaria en un escenario clínico concreto, brindando al lector el estado de la evidencia sobre un procedimiento cuyo margen de utilidad aguarda aún una clara definición.

Summary: Early reopening of the occluded artery paradigm has represented a milestone in the treatment of acute myocardial infarction, and its universal application in cardiological practice lead to a significant reduction in the extension of myocardial injury and mortality from this cause. However, acute coronary occlusion is still a prevalent cause of death and disability; therefore, a lively interest in identificating new procedures, drugs or strategies that contribute to a greater preservation of myocardial tissue persists in this context. Cardiac ischemic preconditioning in its various forms, despite having been object of several studies, both at clinical and experimental levels, is not part of the usual practice of catheterization laboratories, critical cardiology services or mobile emergency units, where myocardial reperfusion is carried out. In this controversy, the authors present arguments for and against the use of remote cardiac ischemic preconditioning as an adjunct to primary angioplasty in a particular clinical stage, providing the reader the status of evidence about a procedure whose profit margin still awaits a clear definition.

O paradigma da reabertura precoce da artéria ocluída representou um marco histórico no tratamento do infarto agudo do miocárdio, e sua aplicação universal na prática cardiológica resultou em uma redução significativa da extensão da lesão miocárdica e da mortalidade por essa causa. No entanto, a oclusão coronariana aguda continua sendo uma causa prevalente de morte e incapacidade de origem cardíaca, persistindo, portanto, a busca de novos métodos, drogas ou estratégias que contribuam para uma maior preservação do tecido miocárdico nesse contexto. Pré-condicionamento cardíaco isquêmico, em suas diversas modalidades, que apesar de ter sido objeto de vários estudos, tanto clínicos como experimentais, não faz parte da prática usual no laboratório de cateterismo cardíaco, nos serviços de cardiologia crítica ou nas unidades móveis de emergência, onde a reperfusão miocárdica é realizada. Nesta controvérsia, os autores apresentam argumentos a favor e contra o uso do pré-condicionamento isquêmico remoto como adjuvante da angioplastia primária em um ambiente clínico específico, proporcionando ao leitor com o estado da evidência em um procedimento cuja margem de utilidade ainda aguarda uma definição clara.

Protección miocárdica por condicionamiento isquémico a distancia en la revascularización coronaria / Myocardial protection by ischemic remote conditioning in coronary revascularization

Introducción: Una serie de breves períodos de isquemias a distancia, previo al evento isquémico mayor, pueden limitar el daño miocárdico producido por la isquemia/reperfusión. Objetivo: Evaluar la utilidad del condicionamiento isquémico a distancia, en pacientes programados para procedimientos quirúrgicos de revascularización coronaria. Métodos: Se realizó un estudio cuasiexperimental, explicativo, comparativo con control histórico, en dos grupos de 247 pacientes, propuestos para revascularización coronaria. Se colocó un torniquete en el brazo derecho, en el grupo estudio, alternando 3 insuflaciones con 3 desinsuflaciones con una presión de 200 mmHg, manteniéndola 5 min cada una. Este proceder se realizó previo, durante y después del evento isquémico mayor, provocado por el pinzamiento de la arteria coronaria. Resultados: Se logró una disminución significativa de los parámetros enzimáticos. No se encontraron diferencias significativas (p>0,05) según un conjunto de variables que representan el estado inicial de los pacientes(AU)

Introduction: A series of short periods of distant ischemia, prior to the major ischemic event, can limit the myocardial damage produced by ischemia or reperfusion. Objective: To evaluate the usefulness of remote ischemic conditioning in patients scheduled for surgical procedures of coronary revascularization. Methods: A quasi-experimental, explanatory, comparative study with historical control was conducted in two groups of 247 patients proposed for coronary revascularization. A tourniquet was placed in the right arm in the study group, alternating 3 insufflations with 3 dessufflations with a pressure of 200 mmHg, keeping each for 5 minutes. This procedure was performed before, during and after the major ischemic event, caused by the impingement of the coronary artery. Results: A significant decrease in enzymatic parameters was achieved. No significant differences were found (p>0.05) according to a set of variables that represent the initial state of the patients(AU)

Impact of Remote Ischemic Conditioning on Circulating miR-208b Level and Cardiac Function in Patients With ST Segment Elevation Myocardial Infarction Undergoing Primary Angioplasty / 中国循环杂志

Objectives: To investigate whether remote ischemic conditioning (RIC) applied to patients with ST-segment elevation myocardial infarction (STEMI) before percutaneous coronary intervention (PCI) could affect circulating miR-208b level or not. Methods:Patients diagnosed with STEMI undergoing PCI from January 2016 to July 2017 were enrolled from the Department of Cardiology, Affiliated Zhongshan Hospital of Dalian University.The patients were randomly allocated to two groups: (1) control group (n=25), PCI alone; (2) RIC group (n=50), PCI combined with RIC (three cycles of 5 min inflation and 5 min deflation of the right lower limb with blood pressure cuff performed before reperfusion). Serum miR-208b was measured before and immediately, at 24 h, and 48 h after PCI with real-time quantitative polymerase chain reaction. Results: The expression of miR-208b was significantly higher immediately post PCI than that before operation in the control group (84.1±9.0 vs 77.8±9.4; P=0.032), while it was significantly lower immediately post PCI than that before operationin RIC group (71.0±9.3 vs 77.4±8.8; P=0.028).miR-208b level was similar before PCI between the control and RIC groups (P=0.874), which was significantly reduced immediately post PCI in RIC group as compared with the control group (P=0.021).The peak value of creatine kinase isoenzyme (CK-MB) in the limb RIC group was significantly lower than that in the control group ([135.2±18.6] U/L vs [167.7±17.2] U/L; P=0.038).The area under the CK-MB curve of the RIC group was significantly smaller than that of the control group ([3 060.7±17.1] U/L vs [3 635.9±15.1] U/L); P=0.047]. The left ventricular ejection fraction (LVEF) in RIC group was significantly higher than that in the control group ([57.8±7.8]% vs [51.9±7.9]%; P=0.003) post PCI. The expression level of serum miR-208b was positively correlated with CK-MB AUC in RIC group (r=0.498, P<0.001). Conclusions: RIC of the lower limb prior to PCI could reduce miR-208b level and improve cardiac functionin STEMI patients.

Remote Ischemic Conditioning by Effluent Collected from a Novel Isolated Hindlimb Model Reduces Infarct Size in an Isolated Heart Model

BACKGROUND AND OBJECTIVES: Experimental protocols for remote ischemic conditioning (RIC) utilize models in which a tourniquet is placed around the hindlimb or effluent is collected from an isolated heart. In analyzing the humoral factors that act as signal transducers in these models, sampled blood can be influenced by systemic responses, while the effluent from an isolated heart might differ from that of the hindlimb. Thus, we designed a new isolated hindlimb model for RIC and tested whether the effluent from this model could affect ischemia/reperfusion (IR) injury and if the reperfusion injury salvage kinase (RISK) and survivor activating factor enhancement (SAFE) pathways are involved in RIC. MATERIALS AND METHODS: After positioning needles into the right iliac artery and vein of rats, Krebs-Henseleit buffer was perfused using a Langendorff apparatus, and effluent was collected. The RIC protocol consisted of 3 cycles of IR for 5 minutes. In the RIC effluent group, collected effluent was perfused in an isolated heart for 10 minutes before initiating IR injury. RESULTS: Compared with the control group, the infarct area in the RIC effluent group was significantly smaller (31.2%±3.8% vs. 20.6%±1.8%, p<0.050), while phosphorylation of signal transducer and activation of transcription-3 (STAT-3) was significantly increased. However, there was a trend of increased phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 in this group. CONCLUSION: This is the first study to investigate the effect of effluent from a new isolated hindlimb model after RIC on IR injury in an isolated heart model. The RIC effluent was effective in reducing the IR injury, and the cardioprotective effect was associated with activation of the SAFE pathway.