Evaluation of the participation of ABCA1 transporter in epicardial and mediastinal adipose tissue from patients with coronary artery disease

ABSTRACT Objective: Recent studies have shown a relationship between adipose tissue and coronary artery disease (CAD). The ABCA1 transporter regulates cellular cholesterol content and reverses cholesterol transport. The aim of this study was to determine the relationship between single nucleotide polymorphisms (SNPs) R230C, C-17G, and C-69T and their expression in epicardial and mediastinal adipose tissue in Mexican patients with CAD. Subjects and methods: The study included 71 patients with CAD and a control group consisting of 64 patients who underwent heart valve replacement. SNPs were determined using TaqMan probes. mRNA was extracted using TriPure Isolation from epicardial and mediastinal adipose tissue. Quantification and expression analyses were done using RT-qPCR. Results: R230C showed a higher frequency of the GG genotype in the CAD group (70.4%) than the control group (57.8%) [OR 0.34, 95% CI (0.14-0.82) p = 0.014]. Similarly, C-17G (rs2740483) showed a statistically significant difference in the CC genotype in the CAD group (63.3%) in comparison to the controls (28.1%) [OR 4.42, 95% CI (2.13-9.16), p = 0.001]. mRNA expression in SNP R230C showed statistically significant overexpression in the AA genotype compared to the GG genotype in CAD patients [11.01 (4.31-15.24) vs. 3.86 (2.47-12.50), p = 0.015]. Conclusion: The results suggest that the GG genotype of R230C and CC genotype of C-17G are strongly associated with the development of CAD in Mexican patients. In addition, under-expression of mRNA in the GG genotype in R230C is associated with patients undergoing revascularization.

La importancia de la determinación de la deuda de oxígeno en el perioperatorio / The importance of oxygen debt determination in the perioperative period

Resumen: El fenómeno de la deuda de oxígeno (dO2) descrito hace varias décadas en el contexto del ejercicio físico se ha incorporado progresivamente al terreno de la medicina. En particular se ha utilizado durante los cambios hemodinámicos producidos por la cirugía y la anestesia en los pacientes de alto riesgo. La dO2 se definió como el aumento en la cantidad de oxígeno consumida por el organismo inmediatamente después de realizar un ejercicio físico hasta que el consumo se normaliza nuevamente. En el perioperatorio se llega a producir cuando se presenta un desbalance entre la oferta (DO2) y la demanda de oxígeno (VO2) que lleva a hipoxia tisular. El grado de la dO2 tisular se ha relacionado directamente con la falla de órganos múltiples y morbimortalidad perioperatoria. A pesar de los avances en la medicina, aún no es posible prevenir o disminuir la dO2 con la administración de líquidos o con el uso de agentes vasoactivos. Por lo que un retardo o manejo inadecuado de la hemodinámica perioperatoria producirá hipoperfusión e hipoxia tisular afectando los resultados de la cirugía. El conocimiento y la valoración de la dO2 es esencial durante la anestesia del paciente de alto riesgo. Para lograr este objetivo se requiere del uso de índices adecuados que permitan detectar y cuantificar la hipoperfusión tisular y el desbalance entre la DO2 y la VO2. En esta revisión se presentan los conceptos fundamentales de la dO2, su mecanismo, detección y cuantificación; además de las intervenciones para evitarla o disminuirla y las recomendaciones para los anestesiólogos con el fin de asegurar mejores resultados en los pacientes quirúrgicos de alto riesgo.

Abstract: The phenomenon of oxygen debt (dO2) described several decades ago in the context of physical exercise has been incorporated into medicine, particularly during the hemodynamic changes produced by surgery and anesthesia in high-risk patients. dO2 is defined as the increase in the amount of oxygen consumed by the body immediately after physical exercise until O2 consumption returns to normal. In the perioperative period, an imbalance between oxygen supply (DO2) and demand (VO2) could generate dO2. The degree of tissue dO2 has been directly related to multiple organ failure and perioperative morbimortality. Despite advances in medicine, it is not yet possible to prevent or lower the dO2 with fluid administration or vasoactive agents. Delay or inadequate management of hemodynamics could produce tissue hypoperfusion and hypoxia, affecting surgery outcomes. Knowledge and assessing dO2 during perioperative are essential during anesthesia for high-risk patients. Adequate indices are required to detect and quantify tissue hypoperfusion and the imbalance between DO2 and VO2 during anesthesia. This review presents the mechanism, detection, and quantification of dO2. In addition to interventions to avoid or reduce dO2 and recommendations for anesthesiologists to ensure better results in high-risk surgical patients.

La lesión miocárdica en el perioperatorio de cirugía no cardíaca / Myocardial injury in the perioperative period of non-cardiac surgery

Resumen: Estudios recientes sobre las causas de muerte en el postoperatorio de cirugía no cardíaca han identificado a la lesión miocárdica como una complicación que se asocia con eventos cardíacos adversos mayores que aumentan la mortalidad a 30 días. La lesión miocárdica se manifiesta como una elevación de las troponinas cardíacas que se produce durante o a los 30 días después de la cirugía, sin que los pacientes presenten síntomas y sin cambios en el electrocardiograma de superficie. En la actualidad, se busca mejorar el diagnóstico oportuno de esta complicación y desarrollar terapias preventivas. En esta revisión abordamos la evidencia de esta lesión, sus mecanismos fisiopatológicos y su manejo.

Abstract: Recent studies on the death causes in the postoperative period of non-cardiac surgery have identified myocardial injury as a complication that is associated with major adverse cardiac events that increase mortality at 30 days after surgery. This kind of myocardial lesion is characterized by the elevation of the cardiac troponins levels during or in the 30 days after the surgery, without symptoms ischemia or changes in the electrocardiogram. Currently, one main goal has been the timely diagnosis of this complication, besides preventive therapies development. The present review article examines the current body of knowledge of this injury, the physiopathological mechanisms and its management.

Myocardial postconditioning: anesthetic considerations / Posacondicionamiento miocárdico: consideraciones anestésicas

Recently, it has been shown that the heart can be protected against the ischemia-reperfusion injury if brief coronary occlusions are performed just at the beginning of the reperfusion. This procedure has been called postconditioning (PostC). It can also be elicited by pharmacologicalinterventions, which are named pharmacological PostC. In general, PostC reduces the reperfusion-induced injury, blunts oxidant-mediated damages and attenuates the local inflammatory response to reperfusion, decreases infarct size, diminishes apoptosis, neutrophil activation, and endothelial dysfunction. The mechanisms that participate in PostC are still not completely understood. In this regard, adenosine, glycine, bradykinin, ciclosporin A are involved in PostC triggering. Similar to ischemic preconditioning, PostC triggers several signaling pathways and molecular components, including nitric oxide (NO), protein kinase C, adenosine triphosphate-sensitive potassium channels, the Reperfusion Injury Salvage Kinases (RISK) pathway, which comprises phosphatidylinositol-3-OH kinase (PI3K) and extracellular signal-regulated kinase (ERK 1/2), and, finally, the Survivor Activating Factor Enhancement (SAFE) pathway. In this review, we describe the mechanisms of reperfusion-induced injury as well as the proposed protective pathways activated by PostC, which seem to converge in inhibition of mitochondrial permeability transition pores opening. On the other hand, experimental evidence indicates that volatile anesthetics and opioids are capable of exerting cardioprotective effects under certain conditions, constituting a very useful pharmacological PostC. Thus, the first minutes of reperfusion represent a window of opportunity for triggering the aforementioned mediators, which acting in concert lead to protection of the myocardium against reperfusion injury. Pharmacological, especially anesthetic, PostC may have a promising future in the clinical scenarios in the operating room.

Recientemente, se ha demostrado que el corazón puede protegerse contra el daño por isquemia-reperfusión si se aplican breves oclusiones coronarias justo al inicio de la reperfusión. Este procedimiento ha sido llamado posacondicionamiento y puede ser producido mediante intervenciones farmacológicas, las cuales constituyen el posacondicionamiento farmacológico. En general, el posacondicionamiento reduce el daño inducido por la reperfusión, disminuyendo el daño oxidativo y atenuando la respuesta inflamatoria local durante la reperfusión, así también disminuye el tamaño del infarto, disminuyendo el proceso de apoptosis, la activación neutrofílica y la disfunción endotelial. Los mecanismos que participan en el posacondicionamiento aún no son bien entendidos, aunque se sabe que moléculas como la adenosina, la glicina, la bradicinina y la ciclosporina A están involucradas en la activación del posacondicionamiento. De manera similar al preacondicionamiento isquémico, el posacondicionamiento activa rutas de señalización en las cuales participan diversos componentes moleculares como el óxido nítrico, la proteína cinasa C, los canales sensibles a ATP, la ruta de aumento del factor de activación de sobrevivencia, así como la ruta de las cinasas de salvamento de la lesión por reperfusión las cuales comprenden la cinasa de fosfatidilinositol-3-0H y la cinasa regulada por señales extracelulares. En esta revisión describimos los mecanismos de daño inducido por la reperfusión así como las vías protectoras propuestas activadas por el posacondicionamiento, las cuales parecen converger en una inhibición de la apertura de los poros de transición de la permeabilidad mitocondrial. Por otro lado, la evidencia experimental indica que los anestésicos volátiles y los opiáceos son capaces de ejercer efectos cardioprotectores bajo ciertas condiciones, constituyendo un posacondicionamiento farmacológico muy útil. De esta manera, los primeros minutos de la reperfusión representan una ventana de oportunidad para activar los mediadores antes mencionados, los cuales actúan en concierto para llevar a la protección del miocardio contra el daño por reperfusión. El posacondicionamiento farmacológico especialmente el anestésico puede tener un futuro promisorio en los escenarios clínicos de las salas de operaciones.

Antiarrhythmic and cardioprotective effects of remifentanil in anesthetized dogs / Efectos antiarrítmicos y cardioprotectores de remifentanil en perros anestesiados

OBJECTIVE: To study the antiarrhythmic effect of remifentanil in experimental arrhythmias in dogs. METHODS: We used dogs weighing 12 kg-18 kg anesthetized with 30 mg/kg sodium pentobarbital given intravenously. Ventricular arrhythmia, ventricular fibrillation and death were induced with digoxin (9 microg/kg/min). In another model, two types of arrhythmia were induced in the right atrium, one of them with aconitine crystals placed on the right atrium and the other was induced in the basement of the right atrium by electrical stimulation. The potential antiarrhythmic action of remifentaniL was investigated in ventricular and atrial arrhythmias by the administration of an intravenous bolus after toxic signs were evident. Thus, two arrhythmias with different mechanisms were generated. Leads DII, unipolar left intraventricular and right atrial leads, and left ventricular pressure were used to record control tracings and tracings in presence of remifentanil, during ventricular arrhythmia. RESULTS: Remifentanil abolished toxic effects of digoxin, it eliminated the A-V dissociation and ventricular extrasystoles, reverting to sinus rhythm in each case. Remifentanil extended the time to reach lethal doses from 63.25 +/- 11.3 to 100 +/- 11.8 min. These effects were blocked by naloxone (0.01 microg/kg) applied before remifentanil. In the two arrhythmias model, remifentanil suppressed both, ectopic focus and atrial flutter. CONCLUSIONS: Remifentanil elicits antiarrhythmic and cardioprotective effects in experimental ventricular arrhythmias induced by digoxin and in a model of two atrial arrhythmias induced by aconitine and by electrical stimulation.

Remodelación cardíaca e inflamación / Cardiac remodeling and inflammation

The cardiac remodeling is a progressive response of the heart to acute and chronic insults regardless its etiology. This process is characterized by changes in the size, shape and function and is associated with a worse prognosis in patients with heart failure. The acute myocardial infarction is the most common cause of remodeling. In the first minutes after injury in the ischemic zone there is an important augment in the synthesis and release of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) interleukin-6 (IL-6), interleukin-1-beta (IL-1beta) and transforming growth factor 1-beta (TGF-1beta). This acute releasing of cytokines could regulate the survival or apoptosis of myocytes in infarcted zone and, their negative inotropic effects could represent an adaptative response to delimit the injury and to decrease myocardial energy demand. This significant upregulation of proinflammatory cytokines can extend to noninfarcted zone and triggers a second phase of elevated levels of cytokines that promote interstitial fibrosis and collagen deposition in the contralateral noninfarcted myocardium leading to a dysfunctional ventricle. This article will review the recent reports that support the idea of a cardioprotective role for this early inflammatory response and a deleterious role of the delayed response that mediate the fibrosis that is a typical feature of the remodeling process.