Precondicionamiento Isquémico Remoto: bases de la protección y resultados clínicos

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.

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.

Protective effect of remote ischemic preconditioning combined with melatonin against cerebral reperfusion injury in rats and the value of multimodal MRI in evaluating the efficacy / 中华放射学杂志

Objective:To explore the possible mechanisms of remote ischemic preconditioning (RIPC) combined with melatonin (MT) against cerebral ischemia-reperfusion injury and to evaluate the value of multimodal MRI.Methods:From December 2021 to December 2022, fifty SPF-grade male SD rats were selected and divided into sham surgery group ( n=10), middle cerebral artery occlusion model group ( n=10), melatonin (MT) group ( n=10), remote ischemic preconditioning (RIPC) group ( n=10) and MT+RIPC group ( n=10). Neurological function scoring and multimodal MRI examinations, including T 2 fluid-attenuated inversion recovery (FLAIR) imaging, diffusion-weighted imaging (DWI), and arterial spin labeling (ASL) imaging, were performed on rats after surgery. After the scans, the rats were euthanized. The brain tissues of 3 rats in each group were randomly selected for HE staining and immunohistochemical staining to observe the pathological morphology of brain tissues and to validate the expression of nuclear factor-E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). The remaining 6 rats were used for enzyme-linked immunosorbent assay to detect levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in brain infarction tissues. ANOVA test or Kruskal-Wallis H test was performed to compare the differences between groups. Results:There were statistically significant differences in neurological function scores and brain infarct volumes among the five groups ( P<0.001). Compared with the sham surgery group, the rats′ neurological function scores and brain infarct volumes were increased in the model group, RIPC group, MT group, and MT+RIPC group ( P<0.05); While compared with the model group, the rats′ neurological function scores and brain infarct volumes were decreased in the RIPC group, MT group, and MT+RIPC group ( P<0.05). MRI showed that abnormal signals were observed on the lesion hemisphere on the right side in rats of the four groups except for the sham surgery group. The lesions showed high signal on T 2 FLAIR and DWI, low signal on apparent diffusion coefficient map, and low perfusion on cerebral blood flow map. Pathological examination showed neuronal nuclear shrinkage in the necrotic area of the brain tissue in the model group, with surrounding neurons exhibiting edema and degeneration. In the RIPC and MT groups, edema and degeneration of neural cells around the infarction area were reduced, while the MT+RIPC group showed primarily neuronal edema with overall structural preservation. The range of Nrf2 and HO-1 protein positivity was significantly increased in the MT+RIPC group compared with the model group. The overall differences in IL-1β, TNF-α and IL-6 levels of 5 groups were statistically significant ( P<0.05), in which IL-1β, TNF-α and IL-6 levels in the model group, RIPC group, MT group, and MT+RIPC group increased compared with the sham-operated group ( P<0.05), and IL-1β, TNF-α, and IL-6 levels decreased in the RIPC group, MT group, and MT+RIPC group compared with the model group ( P<0.05). Conclusion:RIPC+MT exerts antioxidant effects through Nrf2/HO-1 pathway and also exhibits anti-inflammatory properties by reducing levels of IL-1β, IL-6, and TNF-α, thereby alleviating brain edema and neuronal damage, reducing infarct volume and improving neurological deficits in rats with cerebral artery occlusion. The multimodal MRI evaluation demonstrates the value of RIPC+MT in protecting against cerebral ischemia-reperfusion injury.

Comparison of Lower and Upper Limb Remote Ischemic Preconditioning to Prevent Contrast-Induced Nephropathy: A Randomized Pilot Study with a Control Group / Comparación del preacondicionamiento isquémico remoto de la extremidad inferior y superior para evitar la nefropatía inducida por el contraste: Un estudio piloto aleatorizado con un grupo de control

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.

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.

Preconditioning in cardiac anesthesia…… where are we?

Preconditioning, a milestone concept in the cardiovascular sciences introduced 32 years back by Murry. This concept opened a new era in the field of organ protection. To start with extensive studies done on ischemic preconditioning for myocardial protection, ischemic preconditioning is an endogenous science of cellular kinetics. Several components in signal transduction cascade have been identified but still some mechanisms not yet revealed. Anesthetic preconditioning also contributed a lot for myocardial protection and concreted the concept of preconditioning. We, with an inquisitive brain meticulously persuing newer methods of cardioprotection. Remote ischemic preconditioning (RIPC) is a brilliant example of it. RIPC can be future of cardioprotection, clinical trials and studies proved the benefits but yet to conclude the superiority of RIPC over myocardial ischemic cardioprotection. This review is an attempt to reveal this extraordinary concept with its basic cellular kinetics, methods, and recent trends.

Protección renal y hepática por condicionamiento isquémico a distancia en la revascularización miocárdica quirúrgica / Renal and hepatic protection due to remote ischemic conditioning in coronary artery bypass grafting

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.

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.

Remote ischemic preconditioning for prevention of contrast induced nephropathy—Insights from an Indian study

Objectives To study if four cycles of remote ischemic preconditioning (RIPC) could offer protection against contrast induced nephropathy (CIN) and post procedural renal dysfunction in high risk patients undergoing percutaneous coronary intervention (PCI). Methods This was a prospective single blind randomized sham controlled trial where patients undergoing coronary angioplasty with stage III chronic kidney disease were randomized into sham preconditioning and remote ischemic preconditioning. The primary outcome was the reduction in the incidence of CIN. The secondary outcomes were the maximum improvement in eGFR, maximum reduction in serum creatinine and composite of requirement of hemodialysis, death and rehospitalization for heart failure up to 6 weeks after PCI. Results Eleven out of fifty patients in the study group developed CIN (22%) compared to eighteen out of the fifty control patients (36%) (p = 0.123). There was a statistically significant improvement in the post procedure creatinine values at 24 h (p = 0.013), 48 h (p = 0.015), 2 weeks (p = 0.003), 6 weeks (p = 0.003) and post procedure glomerular filtration rate (eGFR) values at 24 h (p = 0.026), 48 h (p = 0.044), 2 weeks (p = 0.015) and 6 weeks (p = 0.011) in study group compared to control group. The secondary outcome composite of requirement of hemodialysis, death and rehospitalization for heart failure was not statistically significant (p: 0.646). Conclusion RIPC does not result in significant reduction of CIN. However RIPC helps in the prevention of post procedural worsening in eGFR and serum creatinine even up to 6 weeks.

Brain-derived neurotrophic factor,Serine/threonine protein kinase Cε,change in mRNA content and remote ischemic preconditioning intervention in rabbit models with spinal cord ischemic reperfusion injury / 临床外科杂志

Objective To investigate the effects of remote ischemic preconditioning(RIPC)on the expression of brain-derived neurotrophic factor(BDNF),Serine/threonine protein kinase Cε(PKCε)in spinal cord tissues and change in mRNA content after spinal cord ischemic reperfusion injury(SCIRI). Methods A total of 36 cases of Japanese white rabbits were randomly divided into sham(group S),is-chemic reperfusion injury(group IR)and group IR+ RIPC(12 rabbits in each group).Each group was further divided into two sub-groups according to time points after reperfusion(2 and 5 days),six rabbits of each group were sacrificed at each time point.In group S,abdominal aorta were only separated and ex-posed and were not camped.In group IR and group IR+RIPC,the abdominal aorta were camped for 30 min,and the SCIRI models were established.In group IR+RIPC,RIPC was performed 1 h before aortic calmping.Hind-limb neurological function of each group was evaluated using Tarlov Scale at 2,5 d after surgery,then rabbits were sacrificed,and L4-L6 spinal cord segments were taken.Pathological change in spinal cord tissues were observed,the protein and mRNA expression of BDNF and PKCε were detected by Western blotting analysis and PT-PCR.Results In comparison with group IR,hind-limb neurologic func-tion scores at the same time point were significantly higher(P<0.05),and the protein and mRNA expres-sion of BDNF and PKCε were significant increased in group IR+RIPC(P<0.05).Conclusion RIPC has an important role in prevention and treatment of SCIRI in rabbits.The mechanisms may be that RIPC activates the PKCε/PKC signaling pathway and up-regulates the expression of BDNF and PKCε in spinal cord tissues after spinal cord injury.

Effect of limb remote ischaemic preconditioning on pulmonary function in patients undergoing cardiac valve replacement surgery with cardiopulmonary bypass / 临床麻醉学杂志

Objective To evaluate the effect of limb remote ischaemic preconditioning on pul-monary function in patients undergoing cardiac valve replacement surgery with cardiopulmonary by-pass.Methods Seventy patients,32 males and 38 females,aged 18-70 years,weighing 45-90 kg, ASA physical status Ⅱ or Ⅲ,scheduled for elective cardiac valve replacement surgery with cardiopul-monary bypass,were divided into 2 groups using a random number table,35 in each group.Patients in group R received three cycles of right upper-limb 5 min ischemia (blood-pressure cuff inflation to≥ 200 mm Hg)and 5 min reperfusion (blood-pressure cuff deflation to 0 mm Hg)at 10 min after in-tubation.In group C,the cuff was placed around the arm but not inflated.At 10 min after intubation (T0),at 1 h after aortic declamping (T1)and at 6 h (T2),12 h (T3),24 h (T4)after surgery,arte-rial blood was sampled to conduct gas analysis,PaO2/FiO2ratio and alveolar-arterial oxygen gradient (A-aDO2)were calculated,and the dynamic lung compliance (Cd)and static lung compliance (Cs) were also recorded.The occurrence of pulmonary adverse events was recorded until discharge. Results Compared with T0,PaO2/FiO2was decreased in the two groups at T1-T4,A-aDO2was de-creased at T2-T4,Cs and Cd were increased in group C at T3,and were increased in group R at T2, T3(P<0.05).Compared with group C,the Cs and Cd at T2,T3were increased in group R.There were no significant differences between the two groups in the PaO2/FiO2,A-aDO2at T0-T4.The oc-currence of the pulmonary adverse events was decreased significantly in group R than in group C (P<0.05).The occurrence of pulmonary adverse events was declined significantly in group R than in group C (P<0.05).Conclusion Limb remote ischemic preconditioning can improve the lung compli-ance and reduce the occurrence of the pulmonary adverse events in patients undergoing cardiac valve replacement surgery.

Precondicionamiento isquémico a distancia en la revascularización miocárdica de los pacientes diabéticos. ¿Es realmente beneficioso? / Remote ischemic preconditioning in myocardial revascularization of diabetic patients. Is it really beneficial?

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)

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)

Role of remote ischemic preconditioning in prevention of contrast induced -nephropathy in elderly patients undergoing coronary artery angiography / 中国基层医药

Objective To explore the role of remote ischemic preconditioning(RIPC)in prevention of contrast -induced nephropathy(CIN)in elderly patients undergoing coronary artery angiography(CAA).Methods 106 elderly patients were enrolled in this randomized control trial.According to random number table,the patients were randomized into control group (n =53)and RIPC group(n =53).All of the patients received 1 000mL of 0.9% sodium chloride injection before CAA.The RIPC group patients underwent RIPC in their right arms with sphygmomanometer cuff infla-tion for 5 minutes prior to the CAA,three cycles were repeated.Serum creatinine was detected before and 48 hours after CAA.Results CIN was reported in 10 cases in the control group and 3 cases in the RIPC group(χ2 =4.30, P =0.04).The levels of serum creatinine were increased[(96.38 ±9.50)μmol/L vs (88.87 ±10.24)μmol/L] after CAA in the control group(t =2.28,P =0.03),and there was no difference in the RIPC group(t =1.17,P =0.24).Conclusion RIPC has a protective effect on CIN in elderly patients in our study.Since this method is harm-less and cost effective,further studies is required to popularize PIPC to our clinical practice for prevention of CIN.

The progress of the mechanism on brain protection of remote ischemic preconditioning / 临床儿科杂志

In recent years, remote ischemic preconditioning is found as a novel way to protect the brain, which may be achieved through nerve pathways, humoral factors or nerve-humoral interaction. The molecular mechanisms for the protection might be related to mitochondria ATP-sensitive potassium channel, mitogen-activated protection kinase, mammalian target of rapamycin, including nitric oxide synthase and cannabinoid receptors. The aim of this review is to explain the mechanism of action of remote ischemic preconditioning on brain protection, as well as the possible direction of clinical application.

Long-term, regular remote ischemic preconditioning improves endothelial function in patients with coronary heart disease

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.

Role of JAK/STAT pathway in cardioprotection of remote ischemic preconditioning / 实用医学杂志

Objective To investigate the effect of remote ischemic preconditioning on myocardial infarction and the involved protective mechanisms. Methods Twenty-four male SD rats were randomly divided into four groups: ischemia-reperfusion (I/R) group, rote ischemic preconditioning (RIPC) group, remote ischemic preconditioning + ischemia-reperfusion (RIPC+I/R) group, and RIPC+AG490+I/R group. The blood samples and myocardial specimens were collected and prepared for tests. The related enzymes were detected and the size of myocardial infarction was measured. The cardiac cells were determined by electron microscopy and light microscopy. Results The size of myocardial infarct and myocardial enzymes were significantly reduced in RIPC+I/R group compared to those in I/R group (P < 0.05). The size of myocardial infarction and myocardial enzymes were significantly increased in AG490 group compared to those in RIPC+I/R group (P < 0.05), but were significantly reduced in AG490 group compared to those in I/R group (P < 0.05). Conclusions Remote ischemic preconditioning may be effective in cardioprotection. The JAK/STAT pathway is involved in the cardioprotection of remote ischemic preconditioning.

Impacto económico del precondicionamiento isquémico remoto en la revascularización miocárdica / Economic impact of remote ischemic preconditioning on myocardial revascularization

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.

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.

Effects of Remote Ischemic Preconditioning on the Expressions of NOS and Akt in the Rat Myocardium / 체질인류학회지

Remote ischemic preconditioning (IP), brief tolerating cycles of ischemia and reperfusion in remote non-vital organs, can reduce ischemic injury of the heart. IP induces cardiac protection by down-regulating iNOS or up-regulating eNOS. In addition, Akt has been known to protect myocardium against ischemia-reperfusion injury. This study was undertaken to observe the expression of iNOS, eNOS, Akt and phospho-Akt (p-Akt) in the rat myocardium after IP. Thirty-five weeks-old male Sprague-Dawley rats were divided into control and IP groups. The IP group was further subdivided into 3 groups based on the number of cycles of IP. For IP, left commom iliac artery was occluded 3, 6 and 10 cycles for 5 min of ischemia alternating with 5 min of reperfusion. The rat were sacrificed at 0, 3, 6, 24 and 72 hours of IP and the heart was removed. The expression of iNOS, eNOS, Akt and p-Akt in the rat myocardium was examined by immunohistochemical staining and Western blot analysis. The expression of iNOS was increased by IP and was higher in 10IP groups than 3IP and 6IP group. The expression of eNOS was increased or decreased by IP and was showed no difference with increasing episode of IP. The expression of Akt was decreased by IP at 24 and 72 hours after reperfusion, and showed no differences with increasing episode of IP. The expression of p-Akt was increased by IP and showed no difference with increasing episode of IP. These results suggest that hind limb ischemic preconditioning provides cardiac protection through up-regulation of eNOS and phosphorylation of Akt, however excessive episodes of remote preconditioning may induce the myocardial ischemic injury through overexpression of iNOS.