RESUMO

El precondicionamiento isquémico remoto es una manera eficaz de disminuir el daño por isquemia y reperfusión en el corazón y otros órganos como cerebro o riñón, en modelos experimentales. Este consiste en realizar entre 3 y 5 ciclos de 5 minutos de isquemia seguidos del mismo tiempo de reperfusión, en un tejido alejado del que se quiere proteger, normalmente una extremidad. Estudios preclínicos en animales indican que la isquemia precondicionante inicia señales nerviosas y humorales en el tejido isquémico remoto, que en el corazón activan mecanismos de protección. La señal nerviosa se origina en fibras sensoriales que a nivel cerebral producen una activación del sistema parasimpático. El nervio vago activa ganglios cardíacos intrínsecos del corazón lo que induce protección. Además, desde el tejido isquémico se liberan a la circulación diferentes mediadores que viajan en forma libre o en vesículas lipídicas (exosomas) que inician vías de señalización protectoras en el corazón. A pesar del éxito del precondicionamiento isquémico remoto en animales de experimentación, su aplicación en seres humanos no ha tenido resultados claros. Esta discrepancia puede deberse a una diversidad de factores tales como la edad, la existencia de otras patologías, uso de fármacos u otros tratamientos que afectan la respuesta de los pacientes. Se requiere un mayor conocimiento de las bases moleculares de este mecanismo de protección para que su aplicación en clínica sea exitosa.

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In experimental models, remote ischemic preconditioning effectively decreases ischemia reperfusion injury to the heart and other organs such as the brain or kidney. It consists of 3 to 5 cycles of 5 minutes of ischemia followed by 5 minutes of reperfusion, in a remote tissue, usually a limb. Preclinical studies in animals indicate that preconditioning ischemia initiates neural and humoral signals in the remote ischemic tissue, which activate protective mechanisms in the heart. The nervous signal originates in sensory fibers that activate the parasympathetic system in the brain. The vagus nerve activates the intrinsic cardiac ganglia of the heart, leading to protection from ischemic injury. Furthermore, mediators are released from the ischemic tissue into the circulation that travels freely or in lipid vesicles (exosomes) to the heart where they initiate protective signaling pathways. Despite the success of remote ischemic preconditioning in experimental animals, its application in humans has not produced clear results. This discrepancy may be due to a variety of factors such as age, the existence of other pathologic processes, or the use of drugs or other treatments that affect the patient´s response. An increased knowledge of the molecular bases of this protective mechanism is required for its clinical application to be successful.

Assuntos

Humanos , Traumatismo por Reperfusão/terapia , Precondicionamento Isquêmico/métodos , Precondicionamento Isquêmico Miocárdico/métodos

RESUMO

Acute kidney injury (AKI) is a global health problem and has recently been recognized as a risk factor for developing chronic kidney disease (CKD). Unfortunately, there are no effective treatments to reduce or prevent AKI, which results in high morbidity and mortality rates. Ischemic preconditioning (IPC) has emerged as a promising strategy to prevent, to the extent possible, renal tissue from AKI. Several studies have used this strategy, which involves short or long cycles of ischemia/reperfusion (IR) prior to a potential fatal ischemic injury. In most of these studies, IPC was effective at reducing renal damage. Since the first study that showed renoprotection due to IPC, several studies have focused on finding the best strategy to activate correctly and efficiently reparative mechanisms, generating different modalities with promising results. In addition, the studies performing remote IPC, by inducing an ischemic process in distant tissues before a renal IR, are also addressed. Here, we review in detail existing studies on IPC strategies for AKI pathophysiology and the proposed triggering mechanisms that have a positive impact on renal function and structure in animal models of AKI and in humans, as well as the prospects and challenges for its clinical application.

Assuntos

Injúria Renal Aguda , Precondicionamento Isquêmico , Traumatismo por Reperfusão , Animais , Humanos , Traumatismo por Reperfusão/prevenção & controle , Rim/fisiologia , Precondicionamento Isquêmico/métodos , Isquemia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle

RESUMO

Introduction: Short episodes of ischemia-reperfusion (IR) in the heart (classical ischemic preconditioning, IPC) or in a limb (remote ischemic preconditioning, RIPC) before a prolonged ischemic episode, reduce the size of the infarct. It is unknown whether IPC and RIPC share common mechanisms of protection. Animals KO for NOX2, a superoxide-producing enzyme, or KO for NLRP3, a protein component of inflammasome, are not protected by IPC. The aim of this study was to investigate if NOX2 or NLRP3 inflammasome are involved in the protection induced by RIPC. Methods: We preconditioned rats using 4 × 5 min periods of IR in the limb with or without a NOX2 inhibitor (apocynin) or an NLRP3 inhibitor (Bay117082). In isolated hearts, we measured the infarct size after 30 min of ischemia and 60 min of reperfusion. In hearts from preconditioned rats we measured the activity of NOX2; the mRNA of Nrf2, gamma-glutamylcysteine ligase, glutathione dehydrogenase, thioredoxin reductase and sulfiredoxin by RT-qPCR; the content of glutathione; the activation of the NLRP3 inflammasome and the content of IL-1ß and IL-10 in cardiac tissue. In exosomes isolated from plasma, we quantified NOX2 activity. Results: The infarct size after IR decreased from 40% in controls to 9% of the heart volume after RIPC. This protective effect was lost in the presence of both inhibitors. RIPC increased NOX2 activity in the heart and exosomes, as indicated by the increased association of p47phox to the membrane and by the increased oxidation rate of NADPH. RIPC also increased the mRNA of Nrf2 and antioxidant enzymes. Also, RIPC increased the content of glutathione and the GSH/GSSG ratio. The inflammasome proteins NLRP3, procaspase-1, and caspase-1 were all increased in the hearts of RIPC rats. At the end of RIPC protocol, IL-1ß increased in plasma but decreased in cardiac tissue. At the same time, IL-10 did not change in cardiac tissue but increased by 70% during the next 50 min of perfusion. Conclusion: RIPC activates NOX2 which upregulates the heart's antioxidant defenses and activates the NLRP3 inflammasome which stimulates a cardiac anti-inflammatory response. These changes may underlie the decrease in the infarct size induced by RIPC.

RESUMO

ABSTRACT Background: The role of remote ischemic preconditioning (RIPC) in preventing the development of contrast-induced nephropathy (CIN) and whether there is a difference between the results of applications of RIPC to the upper or lower extremities has not been adequately demonstrated. Methods: We included the patients who underwent coronary angiography due to stable angina pectoris in this single center, randomized, pilot study. We randomly enrolled a total of 168 patients in one of three groups (60 patients in the upper limb RIPC group, 58 patients in the lower limb RIPC group, and 50 patients in the control group). Results: According to the Acute Kidney Injury Network (AKIN), CIN did not develop in any RIPC patients and developed in 6% of controls (OR: 3.511, 95% CI: 2.757-4.471, p=0.025). According to the European Society of Urogenital Radiology (ESUR) guidelines, CIN developed in 1.7% of RIPC patients and 8% of controls (p=0.065). It was found that creatinine levels increased in the control group and decreased in the RIPC groups (baseline: 0.81±0.19mg/dL and 0.86±0.25mg/dL and control: 0.76±0.17mg/dL and 0.91±0.36mg/ dL, p <0.001). When the upper and lower limb RIPC results were compared, there was no statistically significant difference in the incidence of CIN. In multivariate analyses we found out that baseline eGFR, baseline mean blood pressure, contrast agent volume, and RIPC were independently associated with the development of CIN. Conclusions: RIPC is a practically useful method in preventing CIN in patients undergoing coronary angiography. Upper or lower-limb RIPC applications seem to have a similar effect.

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RESUMEN No se ha demostrado adecuadamente el papel del preacondicionamiento isquémico remoto (RIPC) en la prevención del desarrollo de nefropatía inducida por contraste (NIC) y si existe una diferencia entre los resultados de las aplicaciones de RIPC en las extremidades superiores o inferiores. Se incluyó a los pacientes sometidos a coronariografía por angina de pecho estable en este estudio piloto, aleatorizado, unicéntrico. Inscribimos al azar a un total de 168 pacientes en uno de los tres grupos (60 pacientes en el grupo de RIPC de miembros superiores, 58 pacientes en el grupo de RIPC de miembros inferiores, 50 pacientes en el grupo de control). De acuerdo con la Acute Kidney Injury Network (AKIN), NIC no se desarrolló en ningún paciente con RIPC y se desarrolló en el 6% de los controles (OR: 3,511, IC del 95%: 2,757-4,471, p = 0,025). Según las directrices de la Sociedad Europea de Radiología Urogenital (ESUR), la NIC se desarrolló en el 1,7% de los pacientes con RIPC y en el 8% de los controles (p = 0,065). Se encontró que los niveles de creatinina aumentaron en el grupo de control y disminuyeron en los grupos de RIPC (línea de base: 0,81 ± 0,19 mg / dL y 0,86 ± 0,25 mg / dL y control: 0,76 ± 0,17 mg / dL y 0,91 ± 0,36 mg / dL, p <0,001). Cuando se compararon los resultados de RIPC de miembros superiores e inferiores, no hubo diferencias estadísticamente significativas en la incidencia de NIC. En análisis multivariado descubrimos que la TFGe basal, la presión arterial media basal, el volumen del agente de contraste y la RIPC se asociaron de forma independiente con el desarrollo de NIC. La RIPC es un método prácticamente útil en la prevención de NIC en pacientes sometidos a coronariografía. Las aplicaciones de RIPC de miembros superiores o inferiores parecen tener un efecto similar.

RESUMO

Remote ischemic preconditioning (rIPC) is a cardioprotective phenomenon where brief periods of ischemia followed by reperfusion of one organ/tissue can confer subsequent protection against ischemia/reperfusion injury in other organs, such as the heart. It involves activation of humoral, neural or systemic communication pathways inducing different intracellular signals in the heart. The main purpose of this review is to summarize the possible mechanisms involved in the rIPC cardioprotection, and to describe recent clinical trials to establish the efficacy of these strategies in cardioprotection from lethal ischemia/reperfusion injury. In this sense, certain factors weaken the subcellular mechanisms of rIPC in patients, such as age, comorbidities, medication, and anesthetic protocol, which could explain the heterogeneity of results in some clinical trials. For these reasons, further studies, carefully designed, are necessary to develop a clearer understanding of the pathways and mechanism of early and late rIPC. An understanding of the pathways is important for translation to patients.

Assuntos

Precondicionamento Isquêmico , Traumatismo por Reperfusão Miocárdica , Miocárdio , Miócitos Cardíacos , Animais , Humanos , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia

RESUMO

RESUMEN Introducción: Breves períodos de isquemia a distancia pueden limitar el daño miocárdico producido por la isquemia/reperfusión. Objetivos: Identificar el efecto del condicionamiento isquémico a distancia con fines de protección renal y hepática, relacionado al comportamiento postoperatorio de los niveles de creatinina y transaminasas glutámico-purúvica y glutámico-oxalacética en la revascularización miocárdica quirúrgica. Método: Se realizó un estudio cuasiexperimental, explicativo, comparativo con control histórico, en dos grupos de 247 pacientes cada uno, propuestos para revascularización miocárdica quirúrgica. Se colocó un torniquete en el brazo derecho, en el grupo estudio, alternando 3 insuflaciones (con una presión de 200 mmHg) con 3 desinsuflaciones, durante cinco minutos cada una. Este procedimiento se realizó previo, durante y después de la mayor isquemia inducida, provocada por el pinzamiento de la arteria coronaria. Resultados: Se logró una disminución significativa en los valores de creatinina (p<0,001), transaminasa glutámico-purúvica (p<0,001) y transaminasa glutámico-oxalacética (p<0,05). Conclusiones: El condicionamiento isquémico a distancia es una importante herramienta a tener en cuenta para la protección renal y hepática en la revascularización miocárdica quirúrgica.

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ABSTRACT Introduction: Short periods of distant ischemia can limit myocardial damage caused by ischemia/reperfusion. Objective: To identify the effect of remote ischemic preconditioning in relation to the postoperative behavior of creatinine, glutamic transaminase, puruvic and oxalacetic levels. Method: A quasi-experimental, explanatory, comparative study with historical control was carried out in two groups of 247 patients each; all candidates for coronary artery bypass grafting. A blood-pressure cuff was placed on the right arm in the study group alternating three inflations with three deflations of five minutes at 200 mmHg. This procedure was performed prior to during and after the major ischemic episode caused by the coronary artery impingement. Results: A significant decrease in the values ​​of creatinine, puruvic glutamic transaminase and glutamic oxalacetic transaminase was achieved. Conclusions: Remote ischemic conditioning is an important tool to take into account for renal and hepatic protection in coronary artery bypass grafting.

Assuntos

Precondicionamento Isquêmico , Traumatismo por Reperfusão , Creatinina , Enzimas , Transaminases , Revascularização Miocárdica

RESUMO

Adenosine is involved in classic preconditioning in most species and acts especially through adenosine A1 and A3 receptors. The aim of the present study was to evaluate whether remote ischemic preconditioning (rIPC) activates adenosine A1 receptors and improves mitochondrial function, thereby reducing myocardial infarct size. Isolated rat hearts were subjected to 30 min of global ischemia and 60 min of reperfusion [ischemia-reperfusion (I/R)]. In a second group, before isolation of the heart, a rIPC protocol (3 cycles of hindlimb I/R) was performed. Infarct size was measured with tetrazolium staining, and Akt/endothelial nitric oxide (NO) synthase (eNOS) expression/phosphorylation and mitochondrial function were evaluated after ischemia at 10 and 60 min of reperfusion. As expected, rIPC significantly decreased infarct size. This beneficial effect was abolished only when 8-cyclopentyl-1,3-dipropylxanthine (adenosine A1 receptor blocker) and NG-nitro-l-arginine methyl ester (NO synthesis inhibitor) were administered during the reperfusion phase. At the early reperfusion phase, rIPC induced significant Akt and eNOS phosphorylation, which was abolished by the perfusion with an adenosine A1 receptor blocker. I/R led to impaired mitochondrial function, which was attenuated by rIPC and mediated by adenosine A1 receptors. In conclusion, we demonstrated that rIPC limits myocardial infarct by activation of adenosine A1 receptors at early reperfusion in the isolated rat heart. Interestingly, rIPC appears to reduce myocardial infarct size by the Akt/eNOS pathway and improves mitochondrial function during myocardial reperfusion. NEW & NOTEWORTHY Adenosine is involved in classic preconditioning and acts especially through adenosine A1 and A3 receptors. However, its role in the mechanism of remote ischemic preconditioning is controversial. In this study, we demonstrated that remote ischemic preconditioning activates adenosine A1 receptors during early reperfusion, inducing Akt/endothelial nitric oxide synthase phosphorylation and improving mitochondrial function, thereby reducing myocardial infarct size.

Assuntos

Precondicionamento Isquêmico Miocárdico , Mitocôndrias Cardíacas , Receptor A1 de Adenosina , Antagonistas do Receptor A1 de Adenosina/uso terapêutico , Trifosfato de Adenosina/biossíntese , Animais , Inibidores Enzimáticos/uso terapêutico , Masculino , Potencial da Membrana Mitocondrial , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/fisiopatologia , Traumatismo por Reperfusão Miocárdica/diagnóstico por imagem , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Óxido Nítrico Sintase Tipo III/metabolismo , Nitroarginina/uso terapêutico , Consumo de Oxigênio , Ratos , Ratos Sprague-Dawley , Xantinas/uso terapêutico

RESUMO

ANTECEDENTES: El preacondicionamiento isquémico remoto (PIR) en trasplante hepático ha sido sugerido en el ámbito experimental como estrategia para disminuir la lesión por isquemia- reperfusión. OBJETIVO: Evaluar el efecto del PIR sobre el injerto hepático en donante cadáver y el impacto de diversos mediadores inflamatorios en este proceso. MÉTODO: Se incluyeron 10 receptores de trasplante hepático, 5 controles y 5 con PIR, el cual fue realizado en los donantes cadavéricos mediante la aplicación de un torniquete neumático en ambos muslos por 10 minutos seguido de 10 minutos de reperfusión. Se determinaron interleucina (IL)-1, IL-6, factor de necrosis tumoral alfa (FNT-α), factor de crecimiento endotelial vascular (FCEV) y molécula de adhesión intracelular (ICAM)-1, parámetros hematológicos y bioquímicos en diversas fases del trasplante hepático. RESULTADOS: Se observó un aumento significativo de la aspartato aminotransferasa (AST), la alanino aminotransferasa (ALT) y la fosfatasa alcalina en las fases tempranas tras el trasplante hepático, y a las 72 horas los sujetos con PIR mostraron mejor respuesta, con recuperación de plaquetas, que persistió hasta los 3 meses en este grupo. La IL-6 participa en las fases tempranas de la lesión por isquemia- reperfusión, contrario al FNT-α, que se incrementa hasta el día 7, mientras que la ICAM-1 aumentó en todas las fases. CONCLUSIONES: En este estudio piloto, el PIR disminuyó el daño por lesión por isquemia- reperfusión, aunque el mayor efecto se observó después de 72 horas. BACKGROUND: Remote ischemic preconditioning (RIP) in liver transplantation has been suggested experimentally as a strategy to reduce ischemia-reperfusion injury. OBJECTIVE: Evaluate the effect of RIP on liver graft in cadaveric donors and the impact of various inflammatory mediators in this process. METHOD: Ten liver transplantation recipients, 5 controls and 5 PIR, were made in the cadaver donors by applying a pneumatic tourniquet in the upper third of both thighs for a period of 10 minutes followed by 10 minutes reperfusion. The determination of interleukine (IL)-1, IL-6, tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), intracellular adhesion molecule (ICAM)-1 was performed as well as hematological and biochemical parameters at various stages of liver transplantation. RESULTS: Significant increase of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase in the early stages of post-liver transplantation were observed, after 72 hours subjects who received liver transplantation subjected to RIP they showed a better response, which was also evident in platelet recovery, which persisted until phase 3 months in this group. IL-6 appears to participate in the early stages of the ischemia-reperfusion injury, contrary to TNF-α that increases until day 7 while ICAM-1 was increased in all phases. CONCLUSIONS: In this pilot study the PIR decreased the damage by ischemia-reperfusion injury, although the greatest effect was observed after 72 hours.

Assuntos

Precondicionamento Isquêmico/métodos , Transplante de Fígado , Fígado/irrigação sanguínea , Sobrevivência de Tecidos , Adulto , Citocinas/sangue , Feminino , Humanos , Molécula 1 de Adesão Intercelular/sangue , Masculino , Pessoa de Meia-Idade , Fator A de Crescimento do Endotélio Vascular/sangue

RESUMO

BACKGROUND: Currently viewed as a complementary non-pharmacological intervention for preventing cardiac disorders, long-term aerobic training produces cardioprotection through remote ischemic preconditioning (RIPC) mechanisms. However, RIPC triggered by acute exercise remains poorly understood. Although resistance exercise (RE) has been highly recommended by several public health guidelines, there is no evidence showing that RE mediates RIPC. Hence, we investigated whether RE induces cardiac RIPC through nitric oxide synthase (NOS)-dependent mechanism. METHODS AND RESULTS: Acute RE at 40% of the maximal load augmented systemic nitrite levels, associated with increased cardiac eNOS phosphorylation, without affecting nNOS activity. Using an experimental model of myocardial infarction (MI) through ischemia-reperfusion (IR), RE fully prevented the loss of cardiac contractility and the extent of MI size compared to non-exercised (NE) rats. Moreover, RE mitigated aberrant ST-segment and reduced life-threatening arrhythmias induced by IR. Importantly, inhibition of NOS abolished the RE-mediated cardioprotection. After IR, NE rats showed increased cardiac eNOS activity, associated with reduced dimer/monomer ratio. Supporting the pivotal role of eNOS coupling during MI, non-exercised rats displayed a marked generation of reactive oxygen species (ROS) and oxidative-induced carbonylation of proteins, whereas RE prevented these responses. We validated our data demonstrating a restoration of physiological ROS levels in NE + IR cardiac sections treated with BH4, a cofactor oxidatively depleted during eNOS uncoupling, while cardiac ROS generation from exercised rats remained unchanged, suggesting no physiological needs of supplemental eNOS cofactors. CONCLUSION: Together, our findings strongly indicate that RE mediates RIPC by limiting eNOS uncoupling and mitigates myocardial IR injury.

Assuntos

Precondicionamento Isquêmico/métodos , Óxido Nítrico Sintase Tipo III/metabolismo , Condicionamento Físico Animal/fisiologia , Animais , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/patologia , Western Blotting , Eletrocardiografia , Masculino , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo

Assuntos

Procedimentos Cirúrgicos Cardíacos/métodos , Precondicionamento Isquêmico Miocárdico/métodos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Humanos , Traumatismo por Reperfusão Miocárdica/etiologia , Resultado do Tratamento

RESUMO

Introducción: una serie de breves períodos de isquemias a distancia, previo al evento isquémico mayor, pueden limitar el daño miocárdico producido por la isquemia crítica y el que se produce posreperfusión. Objetivo: demostrar la efectividad del precondicionamiento isquémico a distancia en pacientes diabéticos a los cuales se les realizó revascularización coronaria. Métodos: se realizó un estudio longitudinal prospectivo experimental en dos grupos de 103 pacientes, a los que se les realizó revascularización con injerto de la arteria coronaria. En el grupo de prueba incluido en este estudio, se le colocó al paciente un torniquete el cual se insufló tres veces durante cinco minutos en el brazo no dominante, a una presión de 200 mmHg, previo, durante y después del evento isquémico mayor, el que se correspondió con el pinzamiento de la arteria coronaria. Resultados: no se logró una disminución significativa de la creatinina sérica, glicemia, transaminasas glutámico pirúvica, de la creatinfosfoquinasa-MB, ni del consumo de drogas inotrópicas y vasoactivas. Tampoco en la incidencia de arritmias ventriculares letales, bajo gasto cardiaco fatal y muerte postoperatoria. Conclusiones: el precondicionamiento isquémico a distancia puede ser una importante herramienta a tener en cuenta en la protección anti-isquémica de la revascularización miocárdica, pero no parece ser útil en los pacientes diabéticos acorde a esta investigación(AU)

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Introduction: A series of short periods of ischemia at a distance, prior to the greater ischemic event, may limit myocardial damage caused by severe ischemia and that occurs after reperfusion. Objective: To show the effectiveness of ischemic preconditioning at a distance in diabetic patients who were performed coronary revascularization. Methods: An experimental prospective longitudinal study was carried out in two groups of 103 patients, who were performed revascularization with coronary artery bypass graft. In the test group included in this study, the patient was placed a tourniquet insufflated three times for five minutes in the non-dominant arm, at a pressure of 200 mmHg, prior, during and after the greater ischemic event, which corresponded to the coronary artery clamping. Results: A significant decrease was not achieved in serum creatinine, glucose, glutamic pyruvic transaminase, creatine kinase-MB or in inotropic and vasoactive drugs consumption. Neither did it so in the incidence of lethal ventricular arrhythmias, low cardiac fatal output and postoperative death. Conclusions: Remote ischemic preconditioning can be an important tool for protection of antiischemic myocardial revascularization, but according to this research it may not be useful in diabetic patients(AU)

Assuntos

Humanos , Tecidos/irrigação sanguínea , Precondicionamento Isquêmico/métodos , Revascularização Miocárdica/métodos , Estudos Prospectivos , Estudos Longitudinais , Diabetes Mellitus/cirurgia

RESUMO

Remote ischemic preconditioning (RIPre) can prevent myocardial injury. The purpose of this study was to assess the beneficial effects of long-term regular RIPre on human arteries. Forty patients scheduled for coronary artery bypass graft (CABG) surgery were assigned randomly to a RIPre group (n=20) or coronary heart disease (CHD) group (n=20). Twenty patients scheduled for mastectomy were enrolled as a control group. RIPre was achieved by occluding arterial blood flow 5 min with a mercury sphygmomanometer followed by a 5-min reperfusion period, and this was repeated 4 times. The RIPre procedure was repeated 3 times a day for 20 days. In all patients, arterial fragments discarded during surgery were collected to evaluate endothelial function by flow-mediated dilation (FMD), CD34+ monocyte count, and endothelial nitric oxide synthase (eNOS expression). Phosphorylation levels of STAT-3 and Akt were also assayed to explore the underlying mechanisms. Compared with the CHD group, long-term regular RIPre significantly improved FMD after 20 days (8.5±2.4 vs 4.9±4.2%, P<0.05) and significantly reduced troponin after CABG surgery (0.72±0.31 and 1.64±0.19, P<0.05). RIPre activated STAT-3 and increased CD34+ endothelial progenitor cell counts found in arteries. Long-term, regular RIPre improved endothelial function in patients with CHD, possibly due to STAT-3 activation, and this may have led to an increase in endothelial progenitor cells.

Assuntos

Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença das Coronárias/fisiopatologia , Doença das Coronárias/prevenção & controle , Endotélio Vascular/fisiopatologia , Precondicionamento Isquêmico Miocárdico/métodos , /análise , Western Blotting , Ponte de Artéria Coronária/métodos , Doença das Coronárias/cirurgia , Células Progenitoras Endoteliais , Citometria de Fluxo/métodos , Imuno-Histoquímica , Contagem de Leucócitos , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/prevenção & controle , Óxido Nítrico Sintase Tipo III/análise , Reação em Cadeia da Polimerase em Tempo Real , /análise , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do Tratamento

RESUMO

Introducción: condicionar el corazón para mejorar sus capacidades cardioprotectoras endógenas con el uso de isquemias breves a distancia proporciona un novedoso abordaje potencial a la protección miocárdica durante la cirugía cardiaca. Objetivo: identificar el impacto económico del precondicionamiento isquémico a distancia en los pacientes revascularizados quirúrgicamente. Métodos: se realizó un estudio longitudinal prospectivo experimental en dos grupos de 100 personas, a los que se les realizó revascularización por injerto de la arteria coronaria. Se procedió a colocar un torniquete en el brazo no dominante en quienes se incluyeron en el grupo de estudio prueba, alternando tres insuflaciones con tres desinsuflaciones con una presión de 200 mmHg, manteniéndola por espacio de cinco minutos cada una, este proceder se realizó previo, durante y después del evento isquémico mayor que se corresponde con el pinzamiento de la arteria coronaria. Resultados: se logró una importante disminución del consumo de drogas inotrópicas, vasoactivas y de otros medicamentos ahorrándose una importante suma disminuyendo los costos hospitalarios. Comprobándose además, la disminución en la incidencia de arritmias ventriculares letales, bajo gasto cardiaco fatal y de muerte postoperatoria, en todos los casos muy por debajo de la predicción previamente realizada para estas complicaciones. Conclusiones: el precondicionamiento isquémico a distancia puede ser una importante herramienta a tener en cuenta en la protección antisquémica de la revascularización miocárdica que puede disminuir la morbimortalidad y los costos hospitalarios.

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Background: to condition the heart to improve its endogenous cardioprotective capacity using brief remote ischemia provides a novel potential approach to myocardial protection during cardiac surgery. Objective: to identify the economic impact of remote ischemic preconditioning in surgically revascularized patients. Methods: an experimental prospective longitudinal study was conducted in two groups of 100 people who underwent revascularization by coronary artery graft. A tourniquet was placed on the non-dominant arm in those who were included in the test study group, alternating three insufflations with three desinsufflations with a pressure of 200 mmHg, each one being maintained for five minutes. This procedure was performed prior to, during and after the greater ischemic event that corresponds to the pinching of the coronary artery. Results: an important decrease of the consumption of inotropic, vasoactive and other drugs was achieved, saving an important sum, decreasing hospital costs, and also proving a reduction in the incidence of lethal ventricular arrhythmias, low cardiac output and postoperative death which were, in all cases, below the prediction previously made for these complications. Conclusions: remote ischemic preconditioning can be an important tool to be considered in the antischemic protection of myocardial revascularization that can diminish morbimortality and hospital costs.