Sigma-1 receptor modulation fine-tunes KV1.5 channels and impacts pulmonary vascular function.

KV1.5 channels are key players in the regulation of vascular tone and atrial excitability and their impairment is associated with cardiovascular diseases including pulmonary arterial hypertension (PAH) and atrial fibrillation (AF). Unfortunately, pharmacological strategies to improve KV1.5 channel function are missing. Herein, we aimed to study whether the chaperone sigma-1 receptor (S1R) is able to regulate these channels and represent a new strategy to enhance their function. By using different electrophysiological and molecular techniques in X. laevis oocytes and HEK293 cells, we demonstrate that S1R physically interacts with KV1.5 channels and regulate their expression and function. S1R induced a bimodal regulation of KV1.5 channel expression/activity, increasing it at low concentrations and decreasing it at high concentrations. Of note, S1R agonists (PRE084 and SKF10047) increased, whereas the S1R antagonist BD1047 decreased, KV1.5 expression and activity. Moreover, PRE084 markedly increased KV1.5 currents in pulmonary artery smooth muscle cells and attenuated vasoconstriction and proliferation in pulmonary arteries. We also show that both KV1.5 channels and S1R, at mRNA and protein levels, are clearly downregulated in samples from PAH and AF patients. Moreover, the expression of both genes showed a positive correlation. Finally, the ability of PRE084 to increase KV1.5 function was preserved under sustained hypoxic conditions, as an in vitro PAH model. Our study provides insight into the key role of S1R in modulating the expression and activity of KV1.5 channels and highlights the potential role of this chaperone as a novel pharmacological target for pathological conditions associated with KV1.5 channel dysfunction.

[Prevalence of tobacco consumption among working population after the law 42/2010, Spain]. / Prevalencia de consumo de tabaco en población trabajadora tras la entrada en vigor de la Ley 42/2010.

BACKGROUND: The aim of this study was to analyze the impact on tobacco consumption among working population of the Law 42/2010, which amends smoking regulations in Spain. METHODS: Data were obtained from 413,473 Occupational Health check-ups, conducted between July of 2009 and June of 2011, in the Society for Prevention of a Mutual Insurance Company. We analyzed changes in the biannual percentage of smokers and the magnitude of tobacco consumption among smokers in the overall set of medical check-ups, by gender, age, occupational level (manual vs. non-manual workers), and in the specific occupational subgroup of waiters, barmen and similar workers (chi-square test). RESULTS: In the overall set of medical check-ups, the percentage of smokers decreased by 5% (from 40.3% to 35.3%) over the period of study (p <0.001) and the group of smokers with lower daily consumption (< 10 cigarettes) became the most frequent (p <0.001). In the group of waiters, barmen and similar workers the differences in the biannual percentage of smokers did not reach statistical significance (p =0.07). In this group, smokers of < 10 cigarretes/ day also became the most common consumption group (increasing from 40.5% to 48.8%) and the percentage of 21-40 cigarretes/day decreased from 10.6% to 4% (p =0.008). CONCLUSIONS: These results suggest that the new regulation has been accompanied by a significant reduction in smoking among Spanish workers and strongly support population-level measures against tobacco consumption.

Hemodynamic performance of the Medtronic Mosaic and Perimount Magna aortic bioprostheses: five-year results of a prospectively randomized study.

OBJECTIVE: Clinical outcomes of patients undergoing aortic valve replacement may be influenced by the presence of residual gradients and patient-prosthesis mismatch. The aim of this study was to compare hemodynamic performance and clinical outcomes at 5 years after prospectively randomized porcine versus bovine aortic valve replacement. We also aimed to determine the effects of valve hemodynamics on left ventricular (LV) mass regression. METHODS: A total of 108 patients undergoing aortic valve replacement were randomized to receive either the Medtronic Mosaic (MM) porcine (n=54) or the Edwards Perimount Magna (EPM) bovine pericardial prosthesis (n=54). Clinical outcomes, mean gradients, effective orifice area and LV mass regression were evaluated at 1 and 5 years after surgery. Follow-up echocardiograms were performed on 106 (98%) and 87 (92%) patients, respectively. RESULTS: Preoperative characteristics were similar between groups. Mean aortic annulus diameter and mean implant size were comparable in both groups. At 1 and 5 years, mean transprosthetic gradients were lower in the EPM group: EPM 10.3±3.4mmHg versus MM 16.3 ± 7.6 mmHg (p<0.0001) and EPM 9.6 ± 3.5 mmHg versus MM 16.8 ± 8.7 mmHg (p<0.0001), respectively. Similarly, indexed effective orifice areas (IEOA) at 1 and 5 years were significantly greater in the EPM group: EPM 1.10 ± 0.22 cm(2)m(-2) versus MM 0.96 ± 0.22 cm(2)m(-2) (p<0.004) and EPM 1.02 ± 0.25 cm(2)m(-2) versus MM 0.76 ± 0.19 cm(2)m(-2) (p<0.0001), respectively. At 5 years, the incidence of patient-prosthesis mismatch (IEOA ≤0.85 cm(2)m(-2)) was significantly lower in the EPM group: EPM 22.9% vs MM 73.9% (p<0.0001). Such differences were similar when analysis was stratified by surgically measured annular size and implant valve size. During the first year after surgery, both groups demonstrated similar regression of LV mass index (MM -26.3 ± 43 gm(2) vs EPM -30.1 ± 36 gm(-2); p=0.8); however, at 5 years, regression of LV mass index was significantly greater in the EPM group: (EPM -47.4 ± 35 gm(-2) vs -4.4 ± 36 gm(-2); p<0.0001). Five-year survival was 79.6 ± 4.1% in the MM group and 94.4 ± 2.2% in the EPM group (p=0.03). CONCLUSIONS: At 5 years, the EPM valve was significantly superior to the MM prosthesis with regard to hemodynamic performance, incidence of patient-prosthesis mismatch and regression of LV mass index. The hemodynamic superiority of the EPM prostheses in comparison to MM-prostheses demonstrated at 1 year, increased significantly over time.

Takotsubo cardiomyopathy after elective mitral valve replacement.

Takotsubo cardiomyopathy is a syndrome characterized by transient acute left ventricular dysfunction, electrocardiographic changes that can mimic acute myocardial infarction and minimal release of myocardial enzymes in the absence of obstructive coronary artery disease. Reports of Takotsubo syndrome after cardiac surgery are exceptional. We describe a case of Takotsubo cardiomyopathy in a 68-year-old woman after elective mitral valve replacement. Takotsubo syndrome should be considered in the differential diagnosis of patients presenting cardiogenic shock after cardiac surgery.

[Chronic thromboembolic pulmonary hypertension: surgical treatment with thromboendarterectomy]. / Hipertensión pulmonar tromboembólica crónica: tratamiento mediante tromboendarterectomía quirúrgica.

BACKGROUND AND OBJECTIVES: Pulmonary thromboendarterectomy (PTE) is considered the potential curative treatment for chronic thromboembolic pulmonary hypertension (CTEPH). We analysed the results of the PTE application in our institution. PATIENTS AND METHODS: From February 1996 to December 2007, 30 patients with CTEPH underwent video-assisted PTE. Preoperative hemodynamic data were: systolic pulmonary artery pressure (SPAP) 87+/-17mmHg, mean pulmonary artery pressure (MPAP) 51+/-11mmHg, pulmonary total resistance 1067+/-485dynes x s x cm(-5), pulmonary vascular resistance 873+/-389dynes x s x cm(-5) and cardiac index 2.2+/-0.5l/min/m(2). We analysed the influence of several factors on hospital mortality and survival, and we performed partial analysis of mortality since 2004. RESULTS: PTE resulted in significant improvements in SPAP (P<0.001), MPAP (P=0.001) and cardiac index (P<0.001). Hospital mortality was 17% (5/30) (95% confidence interval, 6%-35%). From 2004, it dropped to 5% (1/20) (95% confidence interval, 0%-25%). Hospital mortality was influenced by preoperative pulmonary total resistance, preoperative pulmonary vascular resistance, postoperative SPAP, reduction of SPAP, reduction of MPAP, reperfusion pulmonary oedema and residual postoperative pulmonary hypertension (P=0.036; P=0.018;P=0.013; P=0.050; P=0.050; P=0.030; P=0.045). Survival after PTE, including hospital mortality, was 76+/-9% at 10 years. Through long-term follow-up, functional status (P=0.001), 6min walking distance (P=0.001), end-diastolic right ventricle size (P<0.001), and tricuspid regurgitation (P<0.001) significantly improved. CONCLUSIONS: PTE effectively reduces pulmonary hypertension and offers CTEPH patients a substantial improvement in survival and quality of life.

Prevalencia de consumo de tabaco en población trabajadora tras la entrada en vigor de la Ley 42/2010 / Prevalence of tobacco consumption among working population after the Law 42/2010, Spain

Fundamentos: El objetivo del presente trabajo consistió en analizar el impacto sobre el consumo de tabaco en población trabajadora de la Ley 42/2010 que modifica la normativa antitabaco en España. Métodos: Se obtuvieron datos de 413.473 reconocimientos médicos de Salud Laboral, realizados entre julio de 2009 y junio de 2011, en la Sociedad de Prevención de una Mutua de Accidentes de Trabajo y Enfermedades Profesionales de la Seguridad Social. Se analizó la evolución semestral del porcentaje de fumadores y la magnitud del consumo de tabaco en el total de reconocimientos, segmentando por sexo, edad, nivel ocupacional (trabajos manuales vs. no manuales) y en el subgrupo específico de camareros, bármanes y asimilados (test de chi2). Resultados: En el total de reconocimientos, el porcentaje de fumadores descendió un 5% (del 40,3% al 35,3%) a lo largo del periodo de estudio (p<0,001) y el grupo de fumadores con menor consumo diario (≤10 cigarrillos) se convirtió en el más frecuente (p<0,001). En el grupo de camareros, bármanes y asimilados las diferencias en el porcentaje semestral de fumadores no alcanzaron significación estadística (p=0,07). En este grupo, los fumadores de ≤10 cigarrillos/día también se convirtieron en el grupo de consumo más frecuente (pasando del 40,5% al 48,8%) y el porcentaje de fumadores de 21-40 cigarrillos/día disminuyó del 10,6% al 4% (p=0,008). Conclusiones: Los resultados sugieren que la nueva normativa se ha acompañado de una importante reducción del tabaquismo entre la población trabajadora española y respaldan fuertemente las medidas de lucha contra el tabaco de alcance poblacional(AU)

Background: The aim of this study was to analyze the impact on tobacco consumption among working population of the Law 42/2010, which amends smoking regulations in Spain. Methods: Data were obtained from 413,473 Occupational Health check-ups, conducted between July of 2009 and June of 2011, in the Society for Prevention of a Mutual Insurance Company. We analyzed changes in the biannual percentage of smokers and the magnitude of tobacco consumption among smokers in the overall set of medical check-ups, by gender, age, occupational level (manual vs. non-manual workers), and in the specific occupational subgroup of waiters, barmen and similar workers (chi-square test). Results: In the overall set of medical check-ups, the percentage of smokers decreased by 5% (from 40.3% to 35.3%) over the period of study (p <0.001) and the group of smokers with lower daily consumption (≤ 10 cigarettes) became the most frequent (p <0.001). In the group of waiters, barmen and similar workers the differences in the biannual percentage of smokers did not reach statistical significance (p =0.07). In this group, smokers of ≤ 10 cigarretes/ day also became the most common consumption group (increasing from 40.5% to 48.8%) and the percentage of 21-40 cigarretes/day decreased from 10.6% to 4% (p =0.008). Conclusions: These results suggest that the new regulation has been accompanied by a significant reduction in smoking among Spanish workers and strongly support population-level measures against tobacco consumption(AU)

Prevalencia de peso insuficiente en trabajadores jóvenes atendidos por la Sociedad de Prevención de Ibermutuamur durante el año 2008 / Underweight prevalence among young workers evaluated by the society for the prevention of ibermutuamur during 2008

Objetivos: El propósito de este trabajo es evaluar la prevalencia del peso insuficiente en población trabajadora activa menor de 25 años por comunidades autónomas españolas. Material y método: Estudio observacional transversal en el que se evaluaron 42.086 trabajadores entre el 1/01/2008 y el 31/12/2008. El peso insuficiente se definió como IMC < 18,5. Resultados: Se encontraron 1.716 casos con peso insuficiente para una prevalencia global del 4,08%; 959 mujeres (8,02%) y 757 hombres (2,51%), con diferencias significativas entre comunidades. Conclusiones: La prevalencia de peso insuficiente encontrada indica que es un problema frecuente al que hay que prestarle atención. Tendría interés incluir este tipo de cribado para la detección temprana de estos casos, con la consiguiente posibilidad de un tratamiento precoz y una mejora de la salud. Recomendamos ontinuar profundizado en este tipo de cribados y aplicar las adecuadas estrategias preventivas (AU)

Objective: The purpose of this study was to evaluate the prevalence of underweight in active working population in Spain by Autonomous Community. Design: This is a cross-sectional study in which workers were studied 42,086 young people between 1/01/2008 and 31/12/2008. Underweight was defined as BMI < 18.5. Results: Of the 42,086 workers studied, 1,716 cases were underweight for an overall prevalence of 4.08%; 959 women (8.02%) and 757 men (2.51%). The differences found between communities were significant. Conclusions: Underweight prevalence among young workers found indicates a common problem that needs attention. Deepened interest to continue such screening and apply appropriate preventive strategies (AU)

Hipertensión pulmonar tromboembólica crónica: tratamiento mediante tromboendarterectomía quirúrgica / Chronic thromboembolic pulmonary hypertension: surgical treatment with thromboendarterectomy

IntroducciónLa tromboendarterectomía pulmonar (TP) constituye el tratamiento potencialmente curativo de la hipertensión pulmonar tromboembólica crónica (HTPTC). Analizamos los resultados de la aplicación de la TP en nuestra institución.Pacientes y métodosEntre febrero de 1996 y diciembre de 2007 se realizó TP videoasistida a 30 pacientes con HTPTC. Los datos hemodinámicos preoperatorios fueron (valores medios±desviación estándar): presión sistólica pulmonar (PSP), 87±17mmHg; presión arterial pulmonar media (PAPm), 51±11mmHg; resistencia pulmonar total, 1.067±485dinas·s·cm–5; resistencia vascular pulmonar, 873±389dinas·s·cm–5, e índice cardíaco, 2,2±0,5l/min/m2. Se han analizado los factores que influyeron en la mortalidad hospitalaria y la supervivencia, además de realizarse un análisis parcial de la mortalidad a partir de 2004.ResultadosTras la TP se objetivó un descenso tanto de la PSP (p<0,001) como de la PAPm (P=0,001) y un aumento del índice cardíaco (p<0,001). La mortalidad hospitalaria registrada fue del 17% (5/30; intervalo de confianza del 95%, 6–35%); a partir de 2004 se redujo al 5% (1/20; intervalo de confianza del 95%, 0–25%). La resistencia pulmonar total y la resistencia vascular pulmonar preoperatorias, la PSP postoperatoria, el descenso porcentual de la PSP y de la PAPm, la presencia de edema de reperfusión y la persistencia de la HTP evidenciaron asociación con la mortalidad hospitalaria (p=0,036; p=0,018; p=0,013; p=0,050; p=0,050; p=0,030; p=0,045, respectivamente). La supervivencia actuarial a 10 años, incluyendo la mortalidad hospitalaria, fue del 76±9%. Durante el seguimiento mejoró la clase funcional (p=0,001), aumentó la distancia recorrida en la prueba de la marcha de 6min (p=0,001) y se redujeron tanto el diámetro telediastólico del ventrículo derecho (p<0,001) como el grado de regurgitación tricuspídea (p<0,001)(AU)

ConclusionesLa TP mejora la hemodinámica pulmonar, prolonga la supervivencia y optimiza el estado funcional de pacientes con HTPTC(AU)

Background and objectivesPulmonary thromboendarterectomy (PTE) is considered the potential curative treatment for chronic thromboembolic pulmonary hypertension (CTEPH). We analysed the results of the PTE application in our institution.Patients and methodsFrom February 1996 to December 2007, 30 patients with CTEPH underwent video-assisted PTE. Preoperative hemodynamic data were: systolic pulmonary artery pressure (SPAP) 87±17mmHg, mean pulmonary artery pressure (MPAP) 51±11mmHg, pulmonary total resistance 1067±485dynes·s·cm–5, pulmonary vascular resistance 873±389dynes·s·cm–5 and cardiac index 2.2±0.5l/min/m2. We analysed the influence of several factors on hospital mortality and survival, and we performed partial analysis of mortality since 2004.ResultsPTE resulted in significant improvements in SPAP (P<0.001), MPAP (P=0.001) and cardiac index (P<0.001). Hospital mortality was 17% (5/30) (95% confidence interval, 6%-35%). From 2004, it dropped to 5% (1/20) (95% confidence interval, 0%-25%). Hospital mortality was influenced by preoperative pulmonary total resistance, preoperative pulmonary vascular resistance, postoperative SPAP, reduction of SPAP, reduction of MPAP, reperfusion pulmonary oedema and residual postoperative pulmonary hypertension (P=0.036; P=0.018;P=0.013; P=0.050; P=0.050; P=0.030; P=0.045). Survival after PTE, including hospital mortality, was 76±9% at 10 years. Through long-term follow-up, functional status (P=0.001), 6min walking distance (P=0.001), end-diastolic right ventricle size (P<0.001), and tricuspid regurgitation (P<0.001) significantly improved.ConclusionsPTE effectively reduces pulmonary hypertension and offers CTEPH patients a substantial improvement in survival and quality of life(AU)