Nuevos antiarrítmicos en la fibrilación auricular

La conveniencia de contar con un acervo farmacológico seguro y eficaz en el tratamiento de la fibrilación auricular ha conducido, por una parte, a una profunda depuración en el amplio grupo de fármacos antiarrítmicos, quedando solamente un número muy restringido de compuestos de comprobada y segura actividad antifibrilatoria. Por otra parte, ha conducido al descubrimiento de nuevos conceptos fisiopatológicos que señalan a su vez novedosos objetivos terapéuticos. En función de estos objetivos se han desarrollado fármacos antiarrítmicos con actividad preferencial y hasta selectiva, sobre canales iónicos propios del miocardio auricular. Entre estos nuevos antiarrítmicos se encuentran la dofetilida, la ibutilida y el compuesto AVE0118. Por otra parte, se marcan nuevas posibilidades provistas por el conocimiento de las cualidades cardioprotectoras-antiarrítmicas del sistema opioidérgico

Niveles urinarios de angiotensina-(1-7) y angiotensina II en pacientes con estenosis aórtica de importante repercusión hemodinámica

Objetivo:Reforzar el conocimiento sobre la fisiopatología de la estenosis aórtica. Métodos: Se compararon los niveles urinarios de angiotensina II y angiotensina-(1-7) entre dos muestras: a) 45 pacientes con estenosis aórtica de importante repercusión hemodinámica, sin hipertensión arterial sistémica y con funciones renal y sistólica ventricular izquierda normales; b) grupo de control con 21 voluntarios sin patología cardiovascular. Hipótesis nula: no habría diferencia entre los niveles urinarios. Resultados:El promedio de la concentración urinaria de angiotensina-(1-7) en pacientes con estenosis aórtica fue 2.102 pmoles/mL y de 5.591 pmoles/mL para el grupo control. La media obtenida en concentración urinaria de angiotensina II fue de 0.704 pmoles/mL en los pacientes con estenosis aórtica y 0.185 pmoles/mL en el grupo control. Utilizando la prueba t de Student determinamos que la diferencia en la concentración urinaria de angiotensina-(1-7) (p = 0.633) y la diferencia en la concentración urinaria de angiotensina II (p = 0.631), fueron estadísticamente significativas. Conclusión:Se documentó una diferencia estadísticamente significativa en los niveles urinarios de angiotensina II y angiotensina-(1-7) dentro del grupo de pacientes con estenosis aórtica de importante repercusión hemodinámica

El extracto acuoso de Viscum album induce la expresión de las sintasas de óxido nítrico inducible y endotelial en corazón aislado y perfundido de cobayo: Evidencia del mecanismo de vasodilatación coronaria

Se evaluó farmacológicamente el efecto de un extracto acuoso de Viscum album en el modelo de corazón aislado y perfundido según Langendorff en corazones de cobayo macho normotensos, registrándose la resistencia vascular coronaria, la presión intraventricular izquierda, la liberación de óxido nítrico en el líquido de perfusión, la producción de guanosín monofosfato cíclico en tejido ventricular y la expresión de las sintasas de óxido nítrico inducible y endotelial por Western Blot, en ausencia y presencia de bloqueantes e inhibidores tales como cloruro de gadolinio 6 µM, Nw-nitro-L-arginina metil éster 100 µM y 1H-[1,2,4]oxadiazolo[4,3 a]quinoxalina-1-ona 10 µM. Se observó que el extracto acuoso de V. album induce un descenso significativo en la resistencia vascular coronaria, la cual cursa con incrementos sustanciales en la producción de óxido nítrico y guanosín monofosfato cíclico. El análisis de la expresión de las sintasas de óxido nítrico indicó que el extracto induce significativamente la expresión de ambas isoformas en corazón de cobayo. Tales efectos fueron inhibidos en presencia de los bloqueantes e inhibidores respectivos. Así, la vasodilatación de este extracto está mediada por la vía óxido nítrico/guanilato ciclasa soluble. Adicionalmente, el extracto ejerce un efecto inotrópico positivo mediado por tiramina por un mecanismo de estimulación β1-adrenérgica

Effect of (-)-epicatechin on the modulation of progression markers of chronic renal damage in a 5/6 nephrectomy experimental model

Aims: To evaluate the effects of (-)-epicatechin (Epi) in the progression of kidney damage. Material and methods: We assessed the effects of Epi [0.01–20 mg/kg of body weight/day] during 14 days, in a 5/6 nephrectomy model in mice. Key findings: Nephrectomy-induced systolic arterial hypertension was significantly reduced in a dose dependent manner with Epi treatment. Increased serum creatinine and urea were reduced almost to normal values. The concentration of tetrahydrobiopterin (BH4), used as subrogate of endothelial dysfunction, decreased in nephrectomyzed animals, Epi treatment increased BH4 levels almost reaching normal values. The expression of angiotensin II receptor (AT1-R) and NADPH oxidase-4 (NOX-4) and 3-nitrotyrosine levels increased with nephrectomy and were reduced with Epi treatment. Renal tissue morphology in the remaining tissue was conserved with Epi treatment in a dose dependent manner. Significance.: Chronic kidney disease (CKD) is an independent cardiovascular risk factor associated with a mortality rate 10 to 20 times higher than that of the general population. High blood pressure, endothelial dysfunction and oxidative stress are important factors determining kidney damage progression. Findings of this study indicate that Epi is able to counteract the deleterious effects of subtotal nephrectomy and the structural and functional changes in the remnant kidney tissue, decreasing the progression of CKD. These results warrant the possibility of implement clinical trials to limit the progression of CKD in humans

Antiarrhythmic and cardioprotective effects of remifentanil in anesthetized dogs

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 pen-tobarbital given intravenously. Ventricular arrhythmia, ventricular fibrillation and death were induced with digoxin (9 ug/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 DM, 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 ug/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

Experimental Colitis Is Attenuated by Cardioprotective Diet Supplementation That Reduces Oxidative Stress, Inflammation, and Mucosal Damage

Inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn’s disease (CD) are multifactorial, relapsing disorders of the gastrointestinal tract. However, the etiology is still poorly understood but involves altered immune responses, epithelial dysfunction, environmental factors, and nutrition. Recently, we have shown that the diet supplement corabion has cardioprotective effects due to reduction of oxidative stress and inflammation. Since oxidative stress and inflammation are also prominent risk factors in IBD, we speculated that corabion also has beneficial effects on experimental colitis. Colitis was induced in male mice by administration of 3.5% (w/v) dextran sulfate sodium (DSS) in drinking water for a period of 3 or 7 days with or without daily gavage feeding of corabion consisting of vitamin C, vitamin E, L-arginine, and eicosapentaenoic and docosahexaenoic acid. We found that corabion administration attenuated DSS-induced colon shortening, tissue damage, and disease activity index during the onset of colitis. Mechanistically, these effects could be explained by reduced neutrophil recruitment, oxidative stress, production of proinflammatory cytokines, and internalization of the junctional proteins ZO-1 and E-cadherin leading to less edema formation. Thus, corabion may be a useful diet supplement for the management of chronic inflammatory intestinal disorders such as IBD

Fenofibrate plus Metformin Produces Cardioprotection in a Type 2 Diabetes and Acute Myocardial Infarction Model

We investigated whether fenofibrate, metformin, and their combination generate cardioprotection in a rat model of type 2 diabetes (T2D) and acute myocardial infarction (AMI). Streptozotocin-induced diabetic- (DB-) rats received 14 days of either vehicle, fenofibrate, metformin, or their combination and immediately after underwent myocardial ischemia/reperfusion (I/R). Fenofibrate plus metformin generated cardioprotection in a DBI/R model, reported as decreased coronary vascular resistance, compared to DBI/R-Vehicle, smaller infarct size, and increased cardiac work. The subchronic treatment with fenofibrate plus metformin increased, compared with DBI/R-Vehicle, total antioxidant capacity, manganese-dependent superoxide dismutase activity (MnSOD), guanosine triphosphate cyclohydrolase I (GTPCH-I) expression, tetrahydrobiopterin : dihydrobiopterin (BH4 : BH2) ratio, endothelial nitric oxide synthase (eNOS) activity, nitric oxide (NO) bioavailability, and decreased inducible NOS (iNOS) activity. These findings suggest that PPARα activation by fenofibrate + metformin, at low doses, generates cardioprotection in a rat model of T2D and AMI and may represent a novel treatment strategy to limit I/R injury in patients with T2D