Molecular Alterations of Nucleocytoplasmic Transport in Patients on the Heart Transplantation Waiting List and Its Correlation With the Severity and Etiology of Heart Failure.

OBJECTIVES: To evaluate whether the levels of some molecules implicated in nucleocytoplasmic transport in human cardiomyocytes are related to the severity of heart failure (HF) in patients on the heart transplantation (HT) waiting list, and to determine whether there is a differential pattern of molecular alteration between ischemic cardiomyopathy (ICM) and non-ischemic dilated cardiomyopathy (DCM). METHODS: Sixty-three blood samples collected before HT were analyzed to identify the levels of IMPORTIN5 (IMP5); IMPORTINalpha2; ATPaseCaTransp (ATPCa); NUCLEOPORIN153kDa (Nup153); NUCLEOPORIN160kDa (Nup160); RANGTPaseAP1 (RanGAP1) and EXPORTIN4 (EXP4). These data were then compared between patients with advanced HF with or without the need for ventricular support with extracorporeal membrane oxygenation (ECMO) as a bridge for HT, as well as between patients with non-ischemic DCM and patients with ICM. RESULTS: Thirty-three patients had ICM, 26 had non-ischemic DCM, and 4 had heart disease. Seventeen patients required ventricular assistance as a bridge to HT. The levels of ATPCa, RanGAP1, and IMP5 were significantly higher in patients with ECMO, while EXP4 was significantly higher in patients without ECMO. Patients with DCM showed higher levels of IMP5, RanGAP1, and Nup153 than those with ICM. CONCLUSION: Patients with advanced HF in critical condition (with ECMO as a bridge for HT) presented with significantly higher levels of ATPCa, RanGAP1, and IMP5, while patients with DCM had significantly higher levels of RanGAP1, IMP5, and Nup153. It remains to be clarified whether the determination of these molecules would facilitate the early identification of this group or if their alteration occurs as consequence of circulatory support with ECMO.

Incidence of development of obesity after heart transplantation according to the calcineurin inhibitor.

BACKGROUND: Development of obesity after heart transplantation (HT) is a common complication, largely attributed to immunosuppressive therapy. The objective of this study is to compare the incidence of development of obesity after HT, according to the calcineurin inhibitor (CNI) used (cyclosporine [CsA] vs tacrolimus [Tac]). METHODS: We studied 101 consecutive HT patients from November 2006 to December 2010. A diagnosis of overweight-obesity was made by a body mass index of ≥25 kg/m(2), which was assessed before HT and at 1 year after HT. Patients were randomly assigned to the administration of CsA or Tac by a simple randomization method using a computer program (56% received CsA and 44% Tac). RESULTS: Of the 101 patients, 77% were men, and ischemic heart disease was the most common indication for HT. At baseline, there were no differences in weight between groups treated with CsA or Tac. The mean weight for each group was 71.5 ± 12 and 75 ± 14 kg, respectively (P = .2). The weight increase was greater among CsA patients: after HT, the weight gain was 6.9 ± 11 kg in the CsA group, whereas a minimal weight loss of 0.03 ± 14 kg (P = .008) was experienced in the group treated with Tac. The multivariate analysis showed that only CsA treatment was an independent predictor of development of obesity 1 year after HT (odds ratio, 3.84; 95% CI, 1.04-14.21; P = .01). CONCLUSION: Weight gain after HT may be related to the CNI used and CsA seems to be the CNI that produces the greatest increase.

Long-term prognostic implications of metabolic syndrome in heart transplant recipients.

BACKGROUND: Metabolic syndrome (MS) increases the risk of cardiovascular events due to endothelial dysfunction. There are few studies evaluating the impact of MS on the survival of heart transplantation (HTx) patients. AIM: The aim of this study was to study the impact of MS in the early period and on the long-term survival after HTx. MATERIALS AND METHODS: We studied 196 HTx patients with a minimum survival of 1 year post-HTx. A diagnosis of MS was made at 3 months after HTx, if at least 3 of the following criteria were met: triglyceride levels ≥150 mg/dL (or drug treatment for hypertriglyceridemia); high-density lipoprotein cholesterol (HDL-C) <40 mg/dL in men and <50 mg/dL in women (or drug treatment to raise HDL-C levels); diabetes mellitus on drug treatment or fasting glucose levels ≥100 mg/dL; blood pressure ≥130/85 mm Hg (or on antihypertensive drug treatment); and body mass index (BMI) ≥30. We used the Kaplan-Meier method (log-rank test) to calculate long-term survival and Student t and chi-square tests for comparisons. RESULTS: Among 196 patients, 96 developed MS. There were no differences between the groups with versus without MS in recipient gender, underlying etiology, smoking, pre-HTx diabetes, or immunosuppressive regimen. However, differences were observed between groups in age (MS: 53 ± 9 vs non-MS: 50 ± 12 years; P = .001); pre-HTx creatinine (MS: 1.2 ± 0.3 vs non-MS: 1.0 ± 0.4 mg/dL; P = .001); BMI (MS: 27.3 ± 4 vs non-MS: 24.6 ± 4; P = .001); pre-HTx hypertension (MS: 48% vs non-MS: 17%; P < .001); and dyslipidemia (MS: 53% vs non-MS: 37%; P = .023). Long-term survival was better among the non-MS group, but the difference did not reach significance (MS: 2381 ± 110 vs non-MS: 2900 ± 110 days; P = .34). CONCLUSIONS: The development of MS early after HTx is a common complication that affects nearly 50% of HTx patients. The prognostic implication of this syndrome on overall survival might occur in the long term.

Tratamiento metabólico de la cardiopatía isquémica / Metabolic treatment of ischemic cardiopathy

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[Serotonergic activity and harm avoidance in abstinent drug addicts]. / Actividad serotonérgica y evitación de daño en adictos abstinentes a drogas.

INTRODUCTION: The present study was to assess the relationship between the Tridimensional Personality Questionnaire scores and the 5-HT activity in abstinent drug addicts. METHODOLOGY: 16 men who satisfied the DSM-III-R/DSM-IV criteria for substance abuse disorder accomplished the Cloninger's Tridimensional Personality Questionnaire; their serotonergic activity was measured using the Fenfluramine Challenge Test. RESULTS: The Novelty Seeking is the only dimension showing a statistical difference versus a standard healthy sample, while harm avoidance and not the other dimensions was significantly correlated with the prolactin post-fenfluramine peak (r= 0.80, p<0.001). CONCLUSION: This work confirm that drug addicts are high Novelty Seekers and support the hypothesis that Harm Avoidance dimension correlate with serotonergic activity.

Actividad serotonérgica y evitación de daño en adictos abstinentes a drogas / Serotonergic activity and harm avoidance in abstinent drug addicts

Introducción. Este estudio ha valorado la relación entre las dimensiones del Cuestionario de personalidad tridimensional y la actividad 5-HT en un grupo de adictos abstinentes a las drogas. Metodología. Dieciséis sujetos varones que cumplían el criterio DSM-III-R/DSM-IV de desorden de abuso de sustancias fueron evaluados mediante la administración del Cuestionario de personalidad tridimensional; su actividad serotonérgica fue determinada mediante una prueba de provocación con fenfluramina. Resultados. Sólo la dimensión 'buscador de novedad' se diferenciaba estadísticamente de los valores de una población estándar sana, mientras que 'evitación de daño' y no otras dimensiones correlacionó significativamente con los valores de prolactina post-estimulación con fenfluramina (r= 0,80, p< 0,001). Conclusión. Este trabajo confirma que los adictos a las drogas son personas ávidas de experimentar sensaciones nuevas y apoya la hipótesis de que la dimensión 'evitación de daño' se relaciona con la actividad serotonérgica (AU)

¿Es eficaz la trimetazidina en el aturdimiento miocárdico? Estudio experimental en un modelo canino / Is trimetazidine effective in myocardial stunning? An experimental study in dogs

Objetivos. El objetivo del presente estudio fue evaluar la acción de la trimetazidina (TMZ), un fármaco antiisquémico, en el deterioro de la función sistólica que se produce en el miocardio sometido a isquemias breves y repetidas. Métodos. Se han analizado 12 perros mestizos de ambos sexos, randomizados a tratamiento con TMZ durante 7 días (grupo TMZ) o a tratamiento con placebo (grupo control). Se ha realizado un protocolo isquémico consistente en 20 obstrucciones completas de la arteria coronaria descendente anterior de 2 minutos de duración y separadas de 3 minutos de reperfusión entre ellas. Las variables analizadas al final de cada período de oclusión y reperfusión han sido: frecuencia cardíaca (FC), presión ventricular izquierda (PVI), dP/dt y las curvas de función regional de la zona isquémica y de una zona testigo (longitud telediastólica, telesistólica y fracción de acortamiento). Resultados. El grupo placebo está formado por 6 perros, con un peso medio de 30,08 kg; el grupo TMZ está constituido por 6 perros, con un peso medio de 24,25 kg. Los parámetros hemodinámicos (FC, PVI y dP/dt) no presentan diferencias significativas entre ambos grupos, con poca variabilidad de sus valores respecto a los basales en los diferentes procesos de isquemia/reperfusión. La fracción de acortamiento de la zona isquémica experimenta una caída, estadísticamente significativa, durante las sucesivas fases de isquemia en ambas series, alcanzando valores de acinesia/discinesia, con recuperación parcial durante las reperfusiones en el grupo placebo (aturdimiento), mientras que en la serie TMZ la recuperación es completa (64 por ciento frente 94 por ciento).Conclusiones. Nuestro estudio indica que la TMZ mejora la recuperación de la contractilidad miocárdica afectada por isquemias/reperfusiones breves y repetidas, limitando la aparición de miocardio aturdido (AU)

[Ischemic preconditioning. Is it always a beneficial phenomenon?]. / Precondicionamiento isquémico. Es siempre un fenómeno beneficioso?

INTRODUCTION AND OBJECTIVES: Hearts exposed to reversible ischemia stand a subsequent prolonged episode of coronary artery occlusion (ischemic preconditioning) better. The reduction of infarct size by means of preconditioning has been amply demonstrated, but the relationship between preconditioning and contractile function remains less well defined. In this study we assess the effect of a later ischemia on the regional contractility in a stunned-preconditioned myocardium. METHODS: We analyze the shortening fraction in the ischemic (dependent on the left anterior descending coronary artery), periischemic and control zone (dependent on the left circumflex coronary artery), using chronic implants of ultrasonic crystals in 17 adult mongrel dogs. In the control series, we quantified the effects of partial (30-60% reduction of coronary flow from the basal) and transitory (15 minutes) ischemic episode in the regional myocardial function in a "virgin" myocardium. In two other series, the myocardium was previously stunned-preconditioned through brief and repeated ischemias. Afterwards, at 5th day (series B) and at 15th day (series C), the dogs were subjected to ischemic episode similar to control ones. RESULTS: After comparing the results with the control series, we observed that the shortening fraction of the ischemic zone was decreased by 107% (p < 0.01) during partial ischemic episode when it was induced on the 5th day of the stunning-preconditioning (series B). CONCLUSIONS: In dogs, the brief and repeated episodes of ischemia could condition the contractile function so that a later partial and transitory reduction of coronary flow could induce a severe affectation of contractility expressed as a diskinetic area.

[10-day clinical course of a stunned myocardium model with very short and repeated ischemias]. / Evolución a lo largo de 10 días de un modelo de miocardio aturdido mediante isquemias muy breves y repetidas.

INTRODUCTION AND OBJECTIVES: In previous studies we have observed ischemic processes of very brief duration (2 minutes) and with brief reperfusion (3 minutes), which have been repeated 20 times (ischemic protocol [IP]). They are capable of producing contractile dysfunction of the ischemic zone, with a decrease of 28.6% at 24 hours, and coronary blood flow maintenance (stunning). METHODS: The aim of this study is to examine the evolution of this dysfunction. The IP designed in our laboratory was used on 24 adult mongrel dogs. We measured regional myocardial function using a pair of implanted chronic ultrasonic crystals in the ischemic area (depending on the left anterior descending coronary artery) and a second pair in the control zone (depending on the left circumflex coronary artery). RESULTS: After analyzing results, we found that the shortening fraction decreased to 28.6% (p < 0.05) in 24 hours. During the subsequent five days the shortening fraction decreased to a minimum of 67.88% (p < 0.01), after which there was a progressive recovery that reached 18.95% (NS) below the base-line on the tenth day. We did not observe any significant variation in the hemodynamic parameters at any time. CONCLUSIONS: The repeated, very brief episodes of ischemia (in the experimental terms that we have explained) produced a contractile dysfunction which reached its maximum on the fifth day, and returned to normal on the tenth day. We hypothesize that these alterations could explain the episodes of left ventricular failure with spontaneous recuperation observed in stable myocardial ischemia, and for which no immediate cause has been found.

[Effects of L-carnitine on the regional function of the stunned myocardium caused by ischemia of short duration]. / Efectos de L-carnitina sobre la función regional del miocardio aturdido por isquemias de muy breve duración.

INTRODUCTION AND OBJECTIVES: Myocardial ATP is produced mainly by fatty acid oxidation, a process in which the fatty acid metabolite carrier carnitine is needed to carry the metabolites into the mitochondria. Cardiac ischemia is associated with carnitine depletion. Our objective was to study the functional effect of L-carnitine on myocardium stunned by very brief, repeated ischemias, and to examine its actions in the recovery period. METHODS: The two series studied were the control series (7 dogs) and the carnitine series (7 dogs). L-carnitine was administered to the carnitine series at doses of 250 mg/kg/day starting 7 days before the ischemic protocol and continuing during the follow-up period (10 and 15 days). The ischemic protocol consisted of 20 anterior descending coronary artery occlusions lasting 2 min and with 3 min of reperfusion between occlusions. Global and regional cardiac function parameters were recorded daily. RESULTS: No differences in the global functional (haemodynamic) or ECG of the two series were found, but there were differences in regional myocardial function. The control series segment shortening fraction fell to dyskinesis values during the occlusion periods, then recovered during reperfusions. The segment shortening fraction worsened during the stunning period, reaching its maximal impairment on the 5th day, after which it returned to basal values on the 15th day. The carnitine series showed the same performance in the occlusion/reperfusion period. However, during the stunning period the segment shortening fraction recovered and reached values close to the basal ones maintained them during the follow-up period. CONCLUSIONS: L-carnitine induces an almost immediate recovery of myocardial contractility, when it has been affected by very brief, repeated coronary occlusions. It limits the myocardial stunning apparition.