Ivabradine in acute heart failure: Effects on heart rate and hemodynamic parameters in a randomized and controlled swine trial.

BACKGROUND: Acute heart failure patients could benefit from heart rate reduction, as myocardial consumption and oxidative stress are related to tachycardia. Ivabradine could have a clinical role attenuating catecholamine-induced tachycardia. The aim of this study was to evaluate hemodynamic effects of ivabradine in a swine model of acute heart failure. METHODS: Myocardial infarction was induced by 45 min left anterior descending artery balloon occlusion in 18 anesthetized pigs. An infusion of dobutamine and noradrenaline was maintained aiming to preserve adequate hemodynamic support, accompanied by fluid administration to obtain a pulmonary wedged pressure ≥ 18 mmHg. After reperfusion, rhythm and hemodynamic stabilization, the animals were randomized to 0.3 mg/kg ivabradine intravenously (n = 9) or placebo (n = 9). Hemodynamic parameters were observed over a 60 min period. RESULTS: Ivabradine was associated with a significant reduction in heart rate (88.4 ± 12.0 bpm vs. 122.7 ± 17.3 bpm after 15 min of ivabradine/placebo infusion, p < 0.01) and an increase in stroke volume (68.8 ± 13.7 mL vs. 52.4 ± 11.5 mL after 15 min, p = 0.01). There were no significant differences in systemic or pulmonary arterial pressure, or significant changes in pulmonary capillary pressure. However, after 15 min, cardiac output was significantly reduced with ivabradine (-5.2% vs. +15.0% variation in ivabradine/placebo group, p = 0.03), and central venous pressure increased (+4.2% vs. -19.7% variation, p < 0.01). CONCLUSIONS: Ivabradine reduces heart rate and increases stroke volume without modifying systemic or left filling pressures in a swine model of acute heart failure. However, an excessive heart rate reduction could lead to a decrease in cardiac output and an increase in right filling pressures. Future studies with specific heart rate targets are needed.

Biological evaluation of angular disubstituted naphthoimidazoles as anti-inflammatory agents.

A series of naphthoimidazoles derivatives (3a-3f) were tested for potential anti-inflammatory activity on lipopolysaccharide (LPS)-treated macrophages. Naphthoimidazole 3e exhibited significant inhibitory effects on nitric oxide (NO) production (IC50 <10µM) and decreased the expression of nitric oxide synthase-2 (NOS-2) and cycloxygenase-2 (COX-2) enzymes. It also inhibited the activation of transcription factor NF-κB. Naphthoimidazole 3e might represent a starting point for the synthesis of new anti-inflammatory naphthoimidazoles derivatives.

A labdane diterpene exerts ex vivo and in vivo cardioprotection against post-ischemic injury: involvement of AKT-dependent mechanisms.

Therapeutic approaches to protect the heart from ischemia/reperfusion (I/R) injury are an area of intense research, as myocardial infarction is a major cause of mortality and morbidity. Diterpenes are bioactive natural products with great therapeutic potential. In the present study, we have investigated the in vivo cardioprotective effects of a labdane diterpene (DT1) against cardiac I/R injury and the molecular mechanisms involved. DT1 attenuates post-ischemic injury via an AKT-dependent activation of HIF-1α, survival pathways and inhibition of NF-κB signaling. Myocardial infarction (MI) was induced in Wistar rats occluding the left coronary artery (LCA) for 30min followed by 72h reperfusion. DT1 (5mg/kg) was intravenously administered at reperfusion. In addition, we investigated the mechanisms of cardioprotection in the Langendorff-perfused model. Cardioprotection was observed when DT1 was administered after myocardial injury. The molecular mechanisms involved the activation of the survival pathway PDK-1, AKT and AMPK, a reduced phosphorylation of PKD1/2 and sustained HIF-1α activity, leading to increased expression of anti-apoptotic proteins and decreased caspase-3 activation. Pharmacological inhibition of AKT following MI and prior to DT1 challenge significantly decreased the cardioprotection afforded by DT1 therapy at reperfusion. Cardiac function after MI was significantly improved after DT1-treatment, as evidenced by hemodynamic recovery and decreased myocardial infarct size. These findings demonstrate an efficient in vivo cardioprotection by diterpene DT1 against I/R when administered at reperfusion, opening new therapeutic strategies as adjunctive therapy for the pharmacological management of I/R injury.

Evaluación de la actividad antioxidante de suplementos dietéticos utilizados para mejorar la fertilidad masculina / Assessment of the antioxidant activity of commercial dietary supplements used to improve male fertility

Objetivo: Evaluar la actividad antioxidante de cinco suplementos dietéticos comerciales (AndroMÁS®, Androferti®, Aquilea Fértil®, GestaDha®, Seidiferty®) utilizados para mejorar la fertilidad masculina. Material y Métodos: La actividad antioxidante se determinó mediante dos técnicas estandarizadas en la literatura para suplementos dietéticos: ensayo ORAC (Oxygen Radical Absorbance Capacity) y el ensayo de captación de radical DPPH (diphenylpicryl-hydrazyl). Se analizaron dos lotes de cada suplemento (n=5/lote). Resultados: Los suplementos AndroMÁS y Seidiferty mostraron actividad antioxidante significativa (p<0,05) en el ensayo ORAC con índices ORAC de 0,25 y 0,24 μmol Trolox/mg suplemento, respectivamente, valores comprendidos en el rango descrito en la literatura para suplementos dietéticos antioxidantes (0,0018-3,18 μmol Trolox/mg suplemento). AndroMÁS, Androferti y Seidifertymostraron una significativa actividad captadora de radical DPPH (p<0,05) con valores de inhibición de 97,2 %, 93,0 % y 60,5 %, respectivamente a una concentración de 0,5 mg/ml. Conclusiones: Este estudio sugiere que las propiedades antioxidantes mostradas por AndroMÁS y Seidiferty pueden contribuir a la eficacia terapéutica demostrada en infertilidad masculina (AU)

Objective: To evaluate the antioxidant activity of five commercially available dietary supplements (AndroMÁS ®, Androferti®, Aquilea Fértil®, GestaDha®, Seidiferty®) used to improve male fertility. Material and Methods: Antioxidant activities were determined using two analytical methods standardized in the literature for dietary supplements namely Oxygen Radical Absorbance Capacity (ORAC) and diphenylpicryl-hydrazyl (DPPH) scavenging radical assays. Two batches of each supplement were analyzed. Results: AndroMÁS and Seidiferty showed significant antioxidant properties (p<0.05) as measured by the ORAC assay, with ORAC values of 0.25 and 0.24 μmol Trolox/mg supplement, within the range reported in the literature for dietary antioxidant supplements (0.018- 3.18 μmol of Trolox equivalent/mg of supplement). The DPPH radical scavenging activity was highest in AndroMÁS, Androferti and Seidiferty (97.2%, 93.0% and 60.5%, respectively) at a concentration of 0.5 mg/ml. Conclusions: This study suggests that the antioxidant properties showed by AndroMÁS and Seidiferty could contribute to the therapeutic efficacy on male infertility (AU)