RESUMEN
BACKGROUND: Cardiovascular inflammation and oxidative stress are determining factors in high blood pressure and arrhythmias. Indole-3-carbinol is a cruciferous-derived phytochemical with potential anti-inflammatory and antioxidant effects. However, its implications on the modulation of cardiovascular inflammatory-oxidative markers are unknown. OBJECTIVES: To establish the effects of indole-3-carbinol on the oxidative-inflammatory-proarrhythmic conditions associated with hypertension. MATERIALS: Histological, biochemical, molecular, and functional aspects were evaluated in 1) Culture of mouse BV-2 glial cells subjected to oxidative-inflammatory damage by lipopolysaccharides (100 ng/mL) in the presence or absence of 40 µM indole-3-carbinol (n = 5); 2) Male spontaneously hypertensive rats (SHR) and Wistar Kyoto rats receiving indole-3-carbinol (2000 ppm/day, orally) during the first 8 weeks of life (n = 15); 3) Isolated rat hearts were submitted to 10 min regional ischemia and 10 min reperfusion. RESULTS: 1) lipopolysaccharides induced oxidative stress and increased inflammatory markers; indole-3-carbinol reversed both conditions (interleukin 6, tumor necrosis factor α, the activity of nicotinamide adenine dinucleotide phosphate oxidase, nitric oxide, inducible nitric oxide synthase, heat shock protein 70, all p < 0.01 vs lipopolysaccharides). 2) SHR rats showed histological, structural, and functional changes with increasing systolic blood pressure (154 ± 8 mmHg vs. 122 ± 7 mmHg in Wistar Kyoto rats, p < 0.01); Inflammatory-oxidative markers also increased, and nitric oxide and heat shock protein 70 decreased. Conversely, indole-3-carbinol reduced oxidative-inflammatory markers and systolic blood pressure (133 ± 8 mmHg, p < 0.01 vs. SHR). 3) indole-3-carbinol reduced reperfusion arrhythmias from 8/10 in SHR to 0/10 (p = 0.0007 by Fisher's exact test). CONCLUSIONS: Indole-3-carbinol reduces the inflammatory-oxidative-proarrhythmic process of hypertension. The nitric oxide and heat shock protein 70 are relevant mechanisms of indole-3-carbinol protective actions. Further studies with this pleiotropic phytochemical as a promising cardioprotective are guaranteed.
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Postoperative atrial fibrillation (POAF) complicates 15% to 40% of cardiovascular surgeries. Its incidence progressively increases with aging, reaching 50% in octogenarians. This arrhythmia is usually transient but it increases the risk of embolic stroke, prolonged hospital stay, and cardiovascular mortality. Though many pathophysiological mechanisms are known, POAF prediction is still a hot topic of discussion. Doppler echocardiogram and, lately, strain echocardiography have shown significant capacity to predict POAF. Alterations in oxidative stress, calcium handling, mitochondrial dysfunction, inflammation, fibrosis, and tissue aging are among the mechanisms that predispose patients to the perfect "atrial storm". Manifestations of these mechanisms have been related to enlarged atria and impaired function, which can be detected prior to surgery. Specific alterations in the atrial reservoir and pump function, as well as atrial dyssynchrony determined by echocardiographic atrial strain, can predict POAF and help to shed light on which patients could benefit from preventive therapy.
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Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/fisiopatología , Ecocardiografía/métodos , Anciano , Anciano de 80 o más Años , Puente de Arteria Coronaria/efectos adversos , Femenino , Atrios Cardíacos/fisiopatología , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Periodo Posoperatorio , Valor Predictivo de las Pruebas , Pronóstico , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la EnfermedadAsunto(s)
Tratamiento Farmacológico de COVID-19 , Melatonina/uso terapéutico , Mitocondrias/efectos de los fármacos , Nanoestructuras/uso terapéutico , COVID-19/virología , Humanos , Melatonina/química , Mitocondrias/patología , Mitocondrias/virología , Pandemias , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/patogenicidadRESUMEN
Pharmacological concentrations of melatonin reduce reperfusion arrhythmias, but less is known about the antiarrhythmic protection of the physiological circadian rhythm of melatonin. Bilateral surgical removal of the superior cervical ganglia irreversibly suppresses melatonin rhythmicity. This study aimed to analyze the cardiac electrophysiological effects of the loss of melatonin circadian oscillation and the role played by myocardial melatonin membrane receptors, SERCA2A, TNFα, nitrotyrosine, TGFß, KATP channels, and connexin 43. Three weeks after bilateral removal of the superior cervical ganglia or sham surgery, the hearts were isolated and submitted to ten minutes of regional ischemia followed by ten minutes of reperfusion. Arrhythmias, mainly ventricular tachycardia, increased during reperfusion in the ganglionectomy group. These hearts also suffered an epicardial electrical activation delay that increased during ischemia, action potential alternants, triggered activity, and dispersion of action potential duration. Hearts from ganglionectomized rats showed a reduction of the cardioprotective MT2 receptors, the MT1 receptors, and SERCA2A. Markers of nitroxidative stress (nitrotyrosine), inflammation (TNFα), and fibrosis (TGFß and vimentin) did not change between groups. Connexin 43 lateralization and the pore-forming subunit (Kir6.1) of KATP channels increased in the experimental group. We conclude that the loss of the circadian rhythm of melatonin predisposes the heart to suffer cardiac arrhythmias, mainly ventricular tachycardia, due to conduction disorders and changes in repolarization.
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Arritmias Cardíacas/patología , Ganglionectomía/efectos adversos , Corazón/fisiopatología , Daño por Reperfusión Miocárdica/cirugía , Animales , Arritmias Cardíacas/etiología , Arritmias Cardíacas/metabolismo , Ritmo Circadiano , Conexina 43/genética , Conexina 43/metabolismo , Masculino , Melatonina/metabolismo , Ratas , Ratas Wistar , Receptores de Melatonina/genética , Receptores de Melatonina/metabolismo , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/genética , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismoRESUMEN
Aging leads to structural and electrophysiological changes that increase the risk of postoperative atrial arrhythmias; however, noninvasive preoperative markers of atrial proarrhythmic conditions are still needed. This study is aimed at assessing whether interatrial dyssynchrony determined using two-dimensional speckle tracking echocardiography relates to proarrhythmic structural and functional remodeling. A cohort of 45 patients in sinus rhythm referred for cardiac surgery was evaluated by echocardiography and surface electrocardiogram the day before the intervention. Transmembrane potential, connexin, and potassium channel distribution, inflammatory, and nitrooxidative markers were measured from right atrial tissue obtained from patients. A difference greater than 40 milliseconds between right and left atrial free wall contraction confirmed the presence of interatrial dyssynchrony in 21 patients. No difference in relation with age, previous diseases, and 2-dimensional echocardiographic findings as well as average values of global longitudinal right and left atrial strain were found between synchronic and dyssynchronic patients. Postoperative atrial fibrillation incidence increased from 8.3% in the synchronic group to 33.3% in the dyssynchronic ones. P wave duration showed no difference between groups. Action potentials from dyssynchronous patients decreased in amplitude, maximal rate of depolarization, and hyperpolarized. Duration at 30% of repolarization increased, being markedly shorter at 90% of repolarization. Only the dyssynchronous group showed early and delayed afterdepolarizations. Atrial tissue of dyssynchronous patients displayed lateralization of connexin 40 and increased connexin 43 expression and accumulation of tumor necrosis factor-α in the intercalated disc. Tumor necrosis factor-α did not colocalize, however, with lateralized connexin 40. Nitroxidative marks and KATP channels increased perivascularly and in myocytes. Our results demonstrate that, as compared to a traditional surface electrocardiogram, the novel noninvasive echocardiographic evaluation of interatrial dyssynchrony provides a better identification of nonaged-related proarrhythmic atrial remodeling with increased susceptibility to postoperative atrial fibrillation.
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Arritmias Cardíacas/diagnóstico por imagen , Arritmias Cardíacas/fisiopatología , Remodelación Atrial , Procedimientos Quirúrgicos Cardíacos , Ecocardiografía , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/fisiopatología , Estrés Oxidativo , Potenciales de Acción , Anciano , Arritmias Cardíacas/complicaciones , Arritmias Cardíacas/patología , Fibrilación Atrial/complicaciones , Fibrilación Atrial/fisiopatología , Conexinas/metabolismo , Femenino , Atrios Cardíacos/patología , Humanos , Inflamación/patología , Canales KATP/metabolismo , Masculino , Estrés Nitrosativo , Curva ROC , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Ischemic postconditioning (IPoC) reduces reperfusion arrhythmias but the antiarrhythmic mechanisms remain unknown. The aim of this study was to analyze IPoC electrophysiological effects and the role played by adenosine A1, A2A and A3 receptors, protein kinase C, ATP-dependent potassium (KATP) channels, and connexin 43. IPoC reduced reperfusion arrhythmias (mainly sustained ventricular fibrillation) in isolated rat hearts, an effect associated with a transient delay in epicardial electrical activation, and with action potential shortening. Electrical impedance measurements and Lucifer-Yellow diffusion assays agreed with such activation delay. However, this delay persisted during IPoC in isolated mouse hearts in which connexin 43 was replaced by connexin 32 and in mice with conditional deletion of connexin 43. Adenosine A1, A2A and A3 receptor blockade antagonized the antiarrhythmic effect of IPoC and the associated action potential shortening, whereas exogenous adenosine reduced reperfusion arrhythmias and shortened action potential duration. Protein kinase C inhibition by chelerythrine abolished the protective effect of IPoC but did not modify the effects on action potential duration. On the other hand, glibenclamide, a KATP inhibitor, antagonized the action potential shortening but did not interfere with the antiarrhythmic effect. The antiarrhythmic mechanisms of IPoC involve adenosine receptor activation and are associated with action potential shortening. However, this action potential shortening is not essential for protection, as it persisted during protein kinase C inhibition, a maneuver that abolished IPoC protection. Furthermore, glibenclamide induced the opposite effects. In addition, IPoC delays electrical activation and electrical impedance recovery during reperfusion, but these effects are independent of connexin 43.
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Arritmias Cardíacas/prevención & control , Conexina 43/fisiología , Poscondicionamiento Isquémico/métodos , Canales KATP/metabolismo , Isquemia Miocárdica/complicaciones , Proteína Quinasa C/metabolismo , Receptores Purinérgicos P1/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Arritmias Cardíacas/etiología , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/patología , Canales KATP/genética , Ratones , Ratones Transgénicos , Proteína Quinasa C/genética , Ratas , Ratas Sprague-Dawley , Receptores Purinérgicos P1/genéticaRESUMEN
Hypokalemia prolongs the QRS and QT intervals, deteriorates intercellular coupling, and increases the risk for arrhythmia. Melatonin preserves gap junctions and shortens action potential as potential antiarrhythmic mechanisms, but its properties under hypokalemia remain unknown. We hypothesized that melatonin protects against low potassium-induced arrhythmias through the activation of its receptors, resulting in action potential shortening and connexin-43 preservation. After stabilization in Krebs-Henseleit solution (4.5 mEq/L K+ ), isolated hearts from Wistar rats underwent perfusion with low-potassium (1 mEq/L) solution and melatonin (100 µmol/L), a melatonin receptor blocker (luzindole, 5 µmol/L), melatonin + luzindole or vehicle. The primary endpoint of the study was the prevention of ventricular fibrillation. Electrocardiography was used, and epicardial action potentials and heart function were measured and analyzed. The ventricular expression, dephosphorylation, and distribution of connexin-43 were examined. Melatonin reduced the incidence of low potassium-induced ventricular fibrillation from 100% to 59%, delayed the occurrence of ventricular fibrillation and induced a faster recovery of sinus rhythm during potassium restitution. Melatonin prevented QRS widening, action potential activation delay, and the prolongation of action potential duration at 50% of repolarization. Other ECG and action potential parameters, the left ventricular developed pressure, and nonsustained ventricular arrhythmias did not differ among groups. Melatonin prevented connexin-43 dephosphorylation and its abnormal topology (lateralization). Luzindole abrogated the protective effects of melatonin on electrophysiological properties and connexin-43 misdistribution. Our results indicate that melatonin receptor activation protects against low potassium-induced ventricular fibrillation, shortens action potential duration, preserves ventricular electrical activation, and prevents acute changes in connexin-43 distribution. All of these properties make melatonin a remarkable antifibrillatory agent.
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Potenciales de Acción/efectos de los fármacos , Conexina 43/metabolismo , Melatonina/farmacología , Miocardio/metabolismo , Potasio/efectos adversos , Receptores de Melatonina/metabolismo , Fibrilación Ventricular/metabolismo , Animales , Masculino , Miocardio/patología , Potasio/farmacología , Ratas , Ratas Wistar , Fibrilación Ventricular/inducido químicamente , Fibrilación Ventricular/patología , Fibrilación Ventricular/fisiopatologíaRESUMEN
Anandamide (AEA), an endogenous cannabinoid, has a relevant antihypertensive effect. However, its cardioprotective role has been barely explored due to unfavorable physico-chemical properties and, sometimes, undesirable psychoactive effects. In this context, drug encapsulation in nanocarriers could overcome the limitations associated with the administration of AEA in free form. The aim of the present study was to encapsulate AEA in poly-ε-caprolactone/Pluronic® F127 nanoparticles (AEA/PCL/PF127 NPs) by means of electrospraying, to characterize their physico-chemical properties and cytocompatibility and to evaluate their effect in an in vivo model of cardiovascular remodeling caused by hypertension. AEA/PCL/PF127 NPs were characterized in terms of morphology, size, polydispersity, Z-potential, hydrophilicity, thermal and spectroscopic properties. Also, the encapsulation and loading efficiencies and in vitro release of AEA were analyzed. AEA/PCL/PF127 NPs (700-1000â¯nm) showed adequate cytocompatibility. For the cardiovascular remodeling studies, normotensive (WKY) and hypertensive (SHR) male rats were treated or not with AEA/PCL/PF127 NPs (5â¯mg/Kg, intraperitoneal injection) weekly for 1â¯month. Inflammatory markers and hemodynamic, structural and cardiac functional parameters were monitored. In SHR, the treatment with AEA/PCL/PF127 NPs reversed all altered cardiovascular markers and parameters (pâ¯<â¯0.05). Overall, nanoformulated AEA obtained by electrospraying proved to be effective for the treatment of hypertension and its comorbidities, especially cardiovascular remodeling.
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Ácidos Araquidónicos/administración & dosificación , Cardiotónicos/administración & dosificación , Endocannabinoides/administración & dosificación , Hipertensión/tratamiento farmacológico , Nanopartículas/administración & dosificación , Alcamidas Poliinsaturadas/administración & dosificación , Células 3T3 , Animales , Ácidos Araquidónicos/química , Proteína C-Reactiva/análisis , Cardiotónicos/química , Supervivencia Celular/efectos de los fármacos , Citocinas/sangre , Composición de Medicamentos , Endocannabinoides/química , Proteínas HSP70 de Choque Térmico/sangre , Hipertensión/sangre , Hipertensión/patología , Masculino , Ratones , Nanopartículas/química , Poloxámero/administración & dosificación , Poloxámero/química , Poliésteres/administración & dosificación , Poliésteres/química , Alcamidas Poliinsaturadas/química , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Remodelación Ventricular/efectos de los fármacosRESUMEN
Lethal ventricular arrhythmias increase in patients with chronic kidney disease that suffer an acute coronary event. Chronic kidney disease induces myocardial remodeling, oxidative stress, and arrhythmogenesis. A manifestation of the relationship between kidney and heart is the concomitant reduction in vitamin D receptor (VDR) and the increase in angiotensin II receptor type 1 (AT1 ). Melatonin has renal and cardiac protective actions. One potential mechanism is the increase in the heat shock protein 70 (Hsp70)-an antioxidant factor. We aim to determine the mechanisms involved in melatonin (Mel) prevention of kidney damage and arrhythmogenic heart remodeling. Unilateral ureteral-obstruction (UUO) and sham-operated rats were treated with either melatonin (4 mg/kg/day) or vehicle for 15 days. Hearts and kidneys from obstructed rats showed a reduction in VDR and Hsp70. Associated with AT1 up-regulation in the kidneys and the heart of UUO rats also increased oxidative stress, fibrosis, apoptosis, mitochondrial edema, and dilated crests. Melatonin prevented these changes and ventricular fibrillation during reperfusion. The action potential lengthened and hyperpolarized in melatonin-treated rats throughout the experiment. We conclude that melatonin prevents renal damage and arrhythmogenic myocardial remodeling during unilateral ureteral obstruction due to a decrease in oxidative stress/fibrosis/apoptosis associated with AT1 reduction and Hsp70-VDR increase.
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Proteínas HSP70 de Choque Térmico/metabolismo , Melatonina/uso terapéutico , Receptor de Angiotensina Tipo 1/metabolismo , Receptores de Calcitriol/metabolismo , Taquicardia Ventricular/tratamiento farmacológico , Taquicardia Ventricular/metabolismo , Actinas/metabolismo , Animales , Apoptosis/efectos de los fármacos , Fibrosis/metabolismo , Proteínas HSP70 de Choque Térmico/genética , Etiquetado Corte-Fin in Situ , Técnicas In Vitro , Riñón/metabolismo , Masculino , Microscopía Electrónica , Microscopía Fluorescente , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Miocardio/metabolismo , NADPH Oxidasas/metabolismo , Ratas , Ratas Endogámicas WKY , Receptor de Angiotensina Tipo 1/genética , Receptores de Calcitriol/genéticaRESUMEN
PURPOSE OF REVIEW: Here, we review the known relations between hypertension and obesity to inflammation and postulate the endogenous protective effect of melatonin and its potential as a therapeutic agent. We will describe the multiple effects of melatonin on blood pressure, adiposity, body weight, and focus on mitochondrial-related anti-inflammatory and antioxidant protective effects. RECENT FINDINGS: Hypertension and obesity are usually associated with systemic and tissular inflammation. The progressive affection of target-organs involves multiple mediators of inflammation, most of them redundant, which make anti-inflammatory strategies ineffective. Melatonin reduces blood pressure, body weight, and inflammation. The mechanisms of action of this ancient molecule of protection involve multiple levels of action, from subcellular to intercellular. Mitochondria is a key inflammatory element in vascular and adipose tissue and a potential pharmacological target. Melatonin protects against mitochondrial dysfunction. Melatonin reduces blood pressure and adipose tissue dysfunction by multiple anti-inflammatory/antioxidant actions and provides potent protection against mitochondria-mediated injury in hypertension and obesity. This inexpensive and multitarget molecule has great therapeutic potential against both epidemic diseases.
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Antiinflamatorios/uso terapéutico , Hipertensión/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Melatonina/uso terapéutico , Obesidad/tratamiento farmacológico , Animales , Antioxidantes/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Humanos , Hipertensión/complicaciones , Hipertensión/fisiopatología , Inflamación/metabolismo , Inflamación/fisiopatología , Mitocondrias/metabolismo , Obesidad/complicaciones , Obesidad/fisiopatología , Estrés Oxidativo/efectos de los fármacosRESUMEN
Metabolic syndrome (MetS) is a risk factor for sudden cardiac death in humans, but animal models are needed for the study of this association. Grape pomace (GP), obtained from the winemaking process, contains phenolic compounds with potential cardioprotective effects. The aim of this study was to evaluate if a high-fat-fructose (HFF) diet facilitates the occurrence of arrhythmias during the reperfusion, and if a GP supplementation could counteract these effects. Wistar rats were fed with control (Ctrl), HFF diet and HFF plus GP (1 g kg-1 day-1) for six weeks. The HFF diet induces characteristic features of MetS (higher systolic blood pressure, dyslipidemia and insulin resistance) which was attenuated by GP supplementation. In addition, HFF induced increased reperfusion arrhythmias that were reduced upon GP supplementation. GP also reduced the non-phosphorylated form of connexin-43 (Cx43) while enhancing heart p-AKT and p-eNOS protein levels and reducing Nox4 levels enhanced by the HFF diet, indicating that GP may increase NO bioavailability in the heart. We found a murine model of MetS with increased arrhythmogenesis and translational value. Furthermore, GP prevents diet-induced heart dysfunction and metabolic alterations. These results highlight the potential utilization of winemaking by-products containing significant amounts of bioactive compounds to prevent/attenuate MetS-associated cardiovascular pathologies.
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Arritmias Cardíacas/tratamiento farmacológico , Dieta Alta en Grasa/efectos adversos , Fructosa/efectos adversos , Preparaciones de Plantas/metabolismo , Vitis/química , Animales , Arritmias Cardíacas/etiología , Arritmias Cardíacas/genética , Arritmias Cardíacas/metabolismo , Conexina 43/genética , Conexina 43/metabolismo , Fructosa/metabolismo , Humanos , Masculino , Síndrome Metabólico/complicaciones , Síndrome Metabólico/genética , Síndrome Metabólico/metabolismo , NADPH Oxidasa 4/genética , NADPH Oxidasa 4/metabolismo , Ratas WistarRESUMEN
Cardiovascular disease is often associated with chronic kidney disease and vice versa; myocardial vitamin D receptors (VDRs) are among the probable links between the 2 disorders. The vitamin D receptor activator paricalcitol protects against some renal and cardiovascular complications. However, the structural and electrophysiological effects of myocardial vitamin D receptor modification and its impact on the response to ischemia-reperfusion are currently unknown. This work attempted to determine whether obstructive nephropathy induced myocardial changes (in rats) linked to vitamin D receptor deficiency and to ventricular arrhythmias in Langendorff-perfused hearts. Unilateral ureteral-obstructed and Sham-operated rats were treated with either paricalcitol (30 ng/kg/d intraperitoneal) or vehicle for 15 days. In 5 hearts from each group, we found that obstructed rats showed a reduction in VDRs and an increase in angiotensin II type 1 receptor expression (messenger RNA and protein), suffered fibrosis (determined by Masson trichrome stain) and myofibril reduction with an increase in mitochondrial size, and had dilated crests (determined by electron microscopy). These changes were reversed by paricalcitol. In 8 additional hearts per group, we found that obstructed rats showed a higher incidence of ventricular fibrillation during reperfusion (after 10 minutes of regional ischemia) than did those treated with paricalcitol. The action potential duration was prolonged throughout the experiment in paricalcitol-treated rats. We conclude that the reduction in myocardial vitamin D receptor expression in obstructed rats might be related to myocardial remodeling associated with an increase in arrhythmogenesis and that paricalcitol protects against these changes by restoring myocardial vitamin D receptor levels and prolonging action potentials.
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Arritmias Cardíacas/tratamiento farmacológico , Ergocalciferoles/uso terapéutico , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Miocardio/patología , Receptores de Calcitriol/deficiencia , Obstrucción Ureteral/complicaciones , Potenciales de Acción , Animales , Circulación Coronaria , Femenino , Miocardio/metabolismo , Ratas , Ratas Endogámicas WKY , Receptor de Angiotensina Tipo 1/análisis , Receptores de Calcitriol/análisis , Obstrucción Ureteral/metabolismoRESUMEN
INTRODUCTION Over the last 40 years, high smoking prevalence has been reported throughout Cuba, including in Cienfuegos city in the central part of the island. OBJECTIVES Determine smoking prevalence and potential associated risk factors in Cienfuegos city for 2010-2011. METHODS A descriptive cross-sectional study was conducted in Cienfuegos city in the context of CARMEN (Collaborative Action for Risk Factor Prevention & Effective Management of Non-communicable Diseases), a PAHO multi-country initiative for a multidimensional approach to chronic non-communicable diseases. Participants totaled 2193 (aged 15-74 years), randomly selected through complex probabilistic three-stage sampling. Variables examined in relation to smoking included age, sex, skin color, civil status and educational level. RESULTS Approximately 25% of those surveyed were smokers (30.3% of men and 21.0% of women). For men, prevalence was highest in the groups aged 25-34 and 55-64 years; for women, in the group aged 45-54 years. Concerning skin color, smoking rates were higher among black and mestizo persons (29.5%); and concerning civil status, higher among those who were separated, widowed or divorced (30.0%). Smoking prevalence fell with higher educational level; in keeping with that trend, the university-educated group had the lowest prevalence (16.2%). CONCLUSIONS Although one in four Cienfuegos residents aged ≥15 years smoked in 2010-2011, prevalence there is lower than in previous surveys. Knowledge of differences observed in age, sex, skin color, civil status and educational level can be useful for planning future smoking prevention and control actions.
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Fumar/epidemiología , Población Urbana , Adolescente , Adulto , Anciano , Estudios Transversales , Cuba/epidemiología , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: In this study, we used vidagliptin(V) to examine the role of the DDP-IV, incretin system component, in the activation of different molecular inflammatory cytokines, NF-kB and VCAM-1 to generate a microenvironment that supports cardiovascular remodeling. METHODS: Male WKY and SHR were separated into five groups: Control, FFR: WKY rats receiving a 10% (w/v) fructose solution during all 12 weeks, SHR, FFHR: SHR receiving a 10% (w/v) fructose solution during all 12 weeks and FFHR+V: (5 mg/kg per day for 6 weeks) (n = 8 each group). Metabolic variables and systolic blood pressure were measured. The TBRAS, eNOS activity, and NAD(P)H oxidase activity were estimated to evaluate oxidative stress. Cardiac and vascular remodeling were evaluated. To assess the cytokine, NF-kB and VCAM-1 immunostaining techniques were used. RESULTS: The FFHR experimental model presents metabolic syndrome criteria, vascular and cardiac remodeling, vascular inflammation due to increased expression of NF-kB, VCAM-1, and pro-atherogenic cytokines. Chronic treatment with V was able to reverse total or partiality of variables studied. CONCLUSIONS: Data demonstrated an important effect of DDP-IV in reducing vascular inflammation, accompanied by a favorable reduction in metabolic and structural parameters.
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Inhibidores de la Dipeptidil-Peptidasa IV/administración & dosificación , Inflamación/tratamiento farmacológico , Síndrome Metabólico/tratamiento farmacológico , Enfermedades Vasculares/tratamiento farmacológico , Animales , Presión Sanguínea , Fructosa/administración & dosificación , Inflamación/complicaciones , Resistencia a la Insulina/genética , Síndrome Metabólico/complicaciones , Síndrome Metabólico/fisiopatología , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Molécula 1 de Adhesión Celular Vascular/metabolismo , Enfermedades Vasculares/complicaciones , Enfermedades Vasculares/fisiopatología , Remodelación Vascular/efectos de los fármacosRESUMEN
Melatonin reduces reperfusion arrhythmias when administered before coronary occlusion, but in the clinical context of acute coronary syndromes, most of the therapies are administered at the time of reperfusion. Patients frequently have physiological modifications that can reduce the response to therapeutic interventions. This work determined whether acute melatonin administration starting at the moment of reperfusion protects against ventricular arrhythmias in Langendorff-perfused hearts isolated from fructose-fed rats (FFR), a dietary model of metabolic syndrome, and from spontaneous hypertensive rats (SHR). In both experimental models, we confirmed metabolic alterations, a reduction in myocardial total antioxidant capacity and an increase in arterial pressure and NADPH oxidase activity, and in FFR, we also found a decrease in eNOS activity. Melatonin (50 µm) initiated at reperfusion after 15-min regional ischemia reduced the incidence of ventricular fibrillation from 83% to 33% for the WKY strain, from 92% to 25% in FFR, and from 100% to 33% in SHR (P = 0.0361, P = 0.0028, P = 0.0013, respectively, by Fisher's exact test, n = 12 each). Although, ventricular tachycardia incidence was high at the beginning of reperfusion, the severity of the arrhythmias progressively declined in melatonin-treated hearts. Melatonin induced a shortening of the action potential duration at the beginning of reperfusion and in the SHR group also a faster recovery of action potential amplitude. We conclude that melatonin protects against ventricular fibrillation when administered at reperfusion, and these effects are maintained in hearts from rats exposed to major cardiovascular risk factors. These results further support the ongoing translation to clinical trials of this agent.
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Antioxidantes/administración & dosificación , Fructosa/administración & dosificación , Melatonina/administración & dosificación , Reperfusión Miocárdica/efectos adversos , Fibrilación Ventricular/prevención & control , Animales , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Hipertensión/complicaciones , Masculino , Potenciales de la Membrana/efectos de los fármacos , Síndrome Metabólico/complicaciones , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Fibrilación Ventricular/etiologíaRESUMEN
Reperfusion arrhythmias are currently attributed to ionic imbalance and oxidative stress. Tamoxifen is a potent antioxidant that also modulates some ionic transport pathways. In this work, we tried to correlate the electrophysiological effects of 1, 2, and 5 µM of tamoxifen with the incidence and severity of arrhythmias appearing on reperfusion after 10 minutes of coronary occlusion in isolated hearts from female rats. All tamoxifen concentrations inhibited the action potential shortening observed in the control hearts during late ischemia (6-10 minutes), whereas 2 and 5 µM also reduced the resting membrane potential depolarization. The incidence of sustained ventricular tachycardia and/or ventricular fibrillation on reperfusion decreased from 10 of 12 (control group) to 5 of 10 (1 µM, P = 0.1718), 4 of 12 (2 µM, P = 0.0361), and 2 of 10 (5 µM, P = 0.0083). The possible role of chloride currents activated by cell swelling in these effects was explored in hearts submitted to a 10-minute hypotonic challenge, where tamoxifen (5 µM) blocked the action potential shortening and the late resting membrane potential depolarization produced by hypotonicity, mimicking its action in late ischemia. Tamoxifen produced a similar increase of the total antioxidant capacity of myocardial samples at all the concentration tested. In conclusion, our data strongly suggest that the antiarrhythmic action of this agent is mediated by its electrophysiological effect derived from modulation of chloride currents activated by cell swelling.
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Antiarrítmicos/farmacología , Antioxidantes/farmacología , Arritmias Cardíacas/prevención & control , Corazón/efectos de los fármacos , Isquemia Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/prevención & control , Tamoxifeno/farmacología , Animales , Antineoplásicos Hormonales/farmacología , Arritmias Cardíacas/etiología , Canales de Cloruro/antagonistas & inhibidores , Oclusión Coronaria/fisiopatología , Fenómenos Electrofisiológicos/efectos de los fármacos , Femenino , Técnicas In Vitro , Potenciales de la Membrana/efectos de los fármacos , Moduladores del Transporte de Membrana/farmacología , Isquemia Miocárdica/etiología , Daño por Reperfusión Miocárdica/fisiopatología , Presión Osmótica/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Moduladores Selectivos de los Receptores de Estrógeno/farmacologíaRESUMEN
The objective of this work was to demonstrate the role of COX-2 enzyme at the vascular in experimental model of metabolic syndrome. SHR male WKY rats were employed; they were distributed in 8 groups (n = 8 each): control (W); W + L: WKY rats receiving 20 mg/kg of lumiracoxib by intraesophageal administration; SHR; SHR + L: SHR + 20 mg/kg of lumiracoxib by intraesophageal administration; Fructose-Fed Rats (FFR): WKY rats receiving 10% (w/v) fructose solution in drinking water during all 12 weeks; FFR + L: FFR + 20 mg/kg of lumiracoxib by intraesophageal administration; Fructose-Fed Hypertensive Rats (FFHR): SHR receiving 10% (w/v) fructose solution in drinking water during all 12 weeks; and FFHR + L: FFHR + 20 mg/kg of lumiracoxib by intraesophageal administration. Metabolic variables, blood pressure, morphometric variables, and oxidative stress variables were evaluated; also MMP-2 and MMP-9 (collagenases), VCAM-1, and NF- κ B by Westernblot or IFI were evaluated. FFHR presented all variables of metabolic syndrome; there was also an increase in oxidative stress variables; vascular remodeling and left ventricular hypertrophy were evidenced along with a significant increase in the expression of the mentioned proinflammatory molecules and increased activity and expression of collagenase. Lumiracoxib was able to reverse vascular remodeling changes and inflammation, demonstrating the involvement of COX-2 in the pathophysiology of vascular remodeling in this experimental model.
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Ciclooxigenasa 2/metabolismo , Síndrome Metabólico/enzimología , Síndrome Metabólico/fisiopatología , Animales , Presión Sanguínea/fisiología , Ciclooxigenasa 2/genética , Masculino , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , FN-kappa B/uso terapéutico , Ratas , Ratas Wistar , Molécula 1 de Adhesión Celular Vascular/genética , Molécula 1 de Adhesión Celular Vascular/metabolismoRESUMEN
AIM: This study tests the hypothesis postulating that metabolic syndrome induced by chronic administration of fructose to spontaneously hypertensive rats (FFHR) generates impairment in vascular repair by endothelial progenitor cells (EPC). MATERIALS AND METHODS: TO CHARACTERIZE THE VASCULAR ADVERSE ENVIRONMENT PRESENT IN THIS EXPERIMENTAL MODEL WE MEASURED: NAD(P)H oxidase activity, eNOS activity, presence of apoptosis in the arterial wall, all these parameters were most affected in the FFHR group. Also, we found decreased level and proliferative capacity of EPC measured by flow cytometry and colonies forming units assay in cultured cells, respectively, in both groups treated with fructose; FFHR (SHR fructose fed rats) and FFR (WKY fructose fed rats) compared with their controls; SHR and WKY. RESULTS: The fructose-fed groups FFR and SHR also showed an incremented number of apoptotic (annexinV+/7AADdim) EPC measured by flow cytometry that returns to almost normal values after eliminating fructose administration. CONCLUSION: Our findings suggest that increased apoptosis levels of EPC generated in this experimental model could bein part the underlying cause for the impaired vascular repair by in EPC.
RESUMEN
Introducción: el poscondicionamiento isquémico (PCI) es una estrategia protectora contra la injuria por reperfusión con propiedades antiarrítmicas. La hipertrofia cardíaca secundaria a la hipertensión arterial aumenta el riesgo de sufrir arritmias y, además, reduce la respuesta a algunos tratamientos. Objetivo: determinar si el efecto antiarrítmico del PCI se mantiene en corazones hipertróficos. Método: los corazones aislados de ratas Wistar Kyoto (WKY) y de ratas espontáneamente hipertensas (SHR) de la misma edad, fueron perfundidos según la técnica de Langendorff y sometidos a 15 min de isquemia regional. Al momento de la reperfusión se dividieron en: a) WKY, b) WKY-PCI, c) SHR, d) SHR-PCI (n=13 por grupo). El PCI consistió en tres ciclos de 30 s de reperfusión y 30 s de isquemia, al inicio de la reperfusión. Se clasificaron las arritmias ventriculares observadas en el ECG. Se estimó la hipertrofia por el peso cardíaco relativo. Resultados: la hipertensión arterial en las ratas SHR provocó hipertrofia miocárdica. Todos los corazones sufrieron una alta incidencia de fibrilación ventricular al inicio de la reperfusión (SHR 92,3% y WKY 77%, ns). El PCI restituyó el ritmo sinusal en los corazones de las ratas normotensas (WKY-PCI 61,5% vs WKY 23,1%, p=0,0236 por test de ji2) y en los de las SHR (SHR-PCI 69,2% vs SHR 15,4%, p=0,0016 test de ji2). Conclusión: el PCI fue capaz de restituir el ritmo sinusal en la mayoría de los corazones que presentaron arritmias ventriculares de reperfusión y el efecto antiarrítmico se mantuvo en corazones hipertróficos provenientes de ratas SHR.
Introduction: ischemic postconditioning (IPC) is a protective strategy against reperfusion injury with antiarrhythmic properties. Cardiac hypertrophy secondary to hypertension increases the risk of arrhythmias and also reduces the response to some treatments. Objective: to determine whether the antiarrhythmic effect of IPC was maintained in hypertrophic hearts. Methods: isolated rat hearts from Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) of the same age, were perfused according to Langendorff technique and subjected to 15 min regional ischemia. At the moment of reperfusion, hearts were divided into: a) WKY, b) WKY-IPC, c) SHR, d) SHR-IPC (each group, n= 13). The IPC consisted of 3 cycles of 30 s of reperfusion and 30 s of ischemia at the onset of reperfusion. Ventricular arrhythmias were diagnosed using ECG records. Hypertrophy was estimated by relative heart weight. Results: hypertension in SHR induce myocardial hypertrophy. All hearts underwent a high incidence of ventricular fibrillation (SHR 92,3% and WKY 77%, ns). IPC restored sinus rhythm in the hearts of normotensive rats (WKY-PCI 61,5% versus WKY 23,1%, p = 0,0236 by chi2 test) and in those from SHR (SHR-PCI 69% versus SHR 15,4%, p = 0,0016 chi2 test). Conclusion: IPC is able to restore sinus rhythm from most of the hearts that developed reperfusion ventricular arrhythmias and the antiarrhythmic effect remains in hypertrophic hearts from SHR rats.
RESUMEN
BACKGROUND: Imbalance in adipocytokines secretion is related to the development of metabolic syndrome (MS). In addition, moderate consumption of red wine (RW) decreases the risk of cardiovascular disease. The aim of this study was to evaluate the effects of moderate consumption of RW or ethanol (E) on adiponectin and resistin expression, and vascular alterations in fructose-fed rats (FFRs) as an experimental model of MS. METHODS: Thirty-day-old male Wistar rats were assigned to control (C), F (10% fructose in drinking water), F+E (4.5 ml/kg), and F+RW (35 ml/kg of Malbec RW containing 4.5 ml/kg E). E and RW were administered during the last 4 weeks of a 10-week period. RESULTS: RW administration to F rats was able to significantly decrease insulin resistance, mesenteric adipose tissue weight, and systolic blood pressure (SBP) compared to F group. F+E only reduced the SBP (P < 0.05 vs. F). F+RW also reduced aortic NAD(P)H-oxidase activity, NAD(P)H subunits Nox4 expression in mesenteric tissue, plasma thiobarbituric acid reactive substances (TBARS), and recovered plasma total antioxidant activity (TAA) compared to F and F+E groups (P < 0.05). Adiponectin expression decreased, whereas resistin, vascular cell adhesion molecules-1 (VCAM-1), and nuclear factor-κB (NF-κB) expression and vascular remodeling in mesenteric arteries were higher in F than in C group (P < 0.05). Only RW was able to partially reverse the aforementioned alterations. CONCLUSION: In this study, Malbec RW, but not alcohol alone, improved the balance of adipocytokines and attenuated the oxidative stress and vascular inflammation in a model of MS, suggesting that nonalcohol components of RW are responsible for the beneficial effects.