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The present study first investigated the mechanisms of vasorelaxation induced by ellagic acid (EA), which is one of the major compounds extracted from the pomegranate in the rat thoracic aorta. Male Wistar rats aged 10 to12 weeks weighing 250-350 g were used for the present study. The animals were killed by decapitation, and thoracic aortas were immediately excised and placed in Krebs solutions, cleaned, and freed from surrounding connective tissue. The isolated arteries were cut into rings (4- to 5-mm long) and placed in 20-mL tissue chambers filled with Krebs solution. Initially, the aortic rings were equilibrated for 60 min until a resting tension of 1.0 gr. After the equilibration period, aortic rings were firstly contracted with phenylephrine to increase tone. Once a stable contraction was achieved, EA (10−8 to 10−4 M) was added cumulatively on aortic rings with or without endothelium into organ bath. To characterize the mechanisms involved in EA-induced vasorelaxant effect, the aortic rings were incubated with each inhibitor added to the bath for 30 min before phenylephrine was added to increase tone. The results of the present study have demonstrated in the rat thoracic aorta that EA causes vasorelaxations, which are partly modulated via endothelium-dependent mechanisms and through inhibition of calcium influx. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Objective: We investigated the role of potassium channels in vasodilatory effect of levosimendan in human internal thoracic arteries. Methods: Samples of redundant internal thoracic arteries obtained from patients undergoing a coronary artery bypass graft surgery were cut into 3mm wide rings and suspended in 20ml organ baths. Isometric tension was continuously measured with an isometric force transducer connected to a computer-based data acquisition system. Results: Levosimendan (10−8–10−5 M) or cromakalim (10−8–10−5 M) produced concentration-dependent relaxation responses in human internal thoracic arteries precontracted by 10−6 M phenylephrine. The relaxant responses to levosimendan did not differ significantly between endothelium-intact and endothelium-denuded preparations. Incubation of human internal thoracic artery rings with adenosine 3′,5′-triphosphate (ATP)-dependent potassium channel blocker glibenclamide (10−6 M) for 30min significantly inhibited the relaxant responses to both levosimendan and cromakalim. The Ca2+-activated potassium channel blocker iberiotoxin (10−7 M) also caused a significant but smaller inhibition on relaxant responses to levosimendan. Incubation of the rings with the voltage-dependent potassium channel blocker 4-aminopyridine (5mM) for 10min did not cause significant alterations in relaxant responses to levosimendan. Conclusions: The findings of this study suggested that levosimendan-induced relaxation responses in human internal thoracic arteries were depended on the activation of ATP-dependent and Ca2+-activated potassium channels. [Copyright &y& Elsevier]

Background: Dobutamina Studio Italiano Multicentrico (Do.S.I.M.) is a prospective, randomized, multicenter interuniversity Italian study aimed at assessing the effects of dobutamine on spontaneous variability of ventricular arrhythmias in sinus rhythm NYHA class III-IV patients with congestive heart failure (CHF)., Methods: Out of 74 pre-hoc estimated CHF patients, 68 (92%) were randomized electively to either being washed out of all active drugs except diuretics (group A) or to continue with the standard regimen including digitalis, diuretics and ACE-inhibitors (group B, standard therapy). In 63 patients, complete Holter data were obtained and are reported here. After 72 hours, in both groups, 48-hour Holter monitoring (Holter 1) was performed. The spontaneous variability of ventricular arrhythmias was assessed by calculating the natural logarithm of the sum of hourly incidences (during 48 consecutive hours) of index events such as the mean heart rate or the various forms of total and either sustained or non-sustained ventricular arrhythmias. The results were then grouped for the first and second 24-hour Holter periods. All patients were submitted to 10 microg/kg/min infusion of dobutamine for 72 hours and 48-hour Holter monitoring (Holter 2) was repeated 24 hours before the end of dobutamine infusion. The incidence of arrhythmia and the distribution of laboratory and echocardiographic variables was also studied in group A and B patients. The data of the two groups along with the intrapatient +/- 95% confidence intervals were pooled, both on and off dobutamine., Results: There was no significant difference between Holter 1 and Holter 2 in the rates of index events in 63 patients with regard to pro-arrhythmic effects. Pro-arrhythmic effects were seen during dobutamine infusion in 21% of cases, an effect which subsided (to 5%) when dobutamine was discontinued. Interestingly, the positive inotropic effects of dobutamine (based on ejection fraction changes) were parallel (22%) to the pro-arrhythmic changes, although they persisted long after dobutamine discontinuation (18%). The pro-arrhythmic effects of dobutamine, both during (5%) as well as after (1%) drug infusion, were unrelated to heart rate changes. The prevalence and incidence of non-sustained ventricular tachycardia due to dobutamine were 47 and 29% respectively., Conclusions: In sinus rhythm patients with severe CHF, dobutamine had chronotropic effects and increased a depressed ejection fraction without significantly increasing arrhythmogenicity.