Role of ivabradine in management of stable angina in patients with different clinical profiles

In chronic stable angina, elevated heart rate contributes to the development of symptoms and signs of myocardial ischaemia by increasing myocardial oxygen demand and reducing diastolic perfusion time. Accordingly, heart rate reduction is a well-known strategy for improving both symptoms of myocardial ischaemia and quality of life (QOL). The heart rate-reducing agent ivabradine, a direct and selective inhibitor of the I f current, decreases myocardial oxygen consumption while increasing diastolic time, without affecting myocardial contractility or coronary vasomotor tone. Ivabradine is indicated for treatment of stable angina and chronic heart failure (HF). This review examines available evidence regarding the efficacy and safety of ivabradine in stable angina, when used as monotherapy or in combination with beta-blockers, in particular angina subgroups and in patients with stable angina with left ventricular systolic dysfunction (LVSD) or HF. Trials involving more than 45 000 patients receiving treatment with ivabradine have shown that this agent has antianginal and anti-ischaemic effects, regardless of age, sex, severity of angina, revascularisation status or comorbidities. This heart rate-lowering agent might also improve prognosis, reduce hospitalisation rates and improve QOL in angina patients with chronic HF and LVSD

Deliberative and epistemic approaches to democracy

Deliberative and epistemic approaches to democracy are two important dimensions of contemporary democratic theory. This chapter studies these dimensions in the emerging ecosystem of civic and political participation tools, and appraises their collective value in a new distinct concept: linked democracy. Linked democracy is the distributed, technology-supported collective decision-making process, where data, information and knowledge are connected and shared by citizens online. Innovation and learning are two key elements of Athenian democracies which can be facilitated by the new digital technologies, and a cross-disciplinary research involving computational scientists and democratic theorists can lead to new theoretical insights of democracy

British press attitudes towards the EU's global presence:from the Russian-Georgian War to the 2009 Copenhagen Summit

This article surveys the way in which British print media have presented the European Union (EU)'s global presence in the international arena by analysing two case studies which reflect two very distinctive areas of EU foreign policy: global climate change policy and the policy towards Russia. It employs frame analysis, allowing for the identification of the way in which the discourse of the press was categorized around a series of central opinions and ideas. Frames underscore the connections made by journalists between different events, policies or phenomena and their possible interpretations. The analysis highlights that acting through the common framework of the EU rather than unilaterally was a strategy preferred by the British press. These findings are in stark contrast with the deep Euroscepticism which characterizes press attitudes towards most policy areas, and is often considered to be rooted in the British political culture, media system, public opinion or the longstanding tradition of viewing the European continent as the other

Neuronal nitric oxide synthase is expressed in rat vascular smooth muscle cells: Activation by angiotensin II in hypertension

The nitric oxide synthase (NOS) inhibitor nitro-L-arginine augmented the contractions to angiotensin (Ang) II in carotid artery rings without endothelium from spontaneously hypertensive rats (SHR) but not normotensive Wistar-Kyoto rats, suggesting the possibility of nonendothelial NOS activity in SHR arteries. In SHR artery without endothelium, the potentiation of Ang II contraction by nitro-L-arginine was prevented by L-arginine, but not by D- arginine, and was observed also in the presence of oxyhemoglobin, monomethyl- L-arginine, and 7-nitroindazole, but not in the presence of aminoguanidine. In further support of NOS activation by Ang II in nonendothelial cells, Ang II but not acetylcholine stimulated cGMP levels by 2-fold in SHR arteries without endothelium; nitro-L-arginine decreased both basal and Ang II- stimulated cGMP levels. When NOS activity in SHR arteries was measured, no calcium-independent L-citrulline formation was detectable, while up to 47% of the total calcium-dependent NOS activity was present in nonendothelial cells. Expression of neuronal NOS was revealed in the media of SHR arteries by immunohistochemistry, Western blot, and reverse transcriptase-polymerase chain reaction. Expression of this NOS isoform was greater in SHR than in Wistar-Kyoto rat preparations. Finally, endothelial NOS was observed in the endothelium, but no detectable levels of inducible NOS were found in these tissues. These results demonstrate the expression of neuronal NOS in rat vascular smooth muscle cells and its activation on stimulation by Ang II in spontaneously hypertensive, but not normotensive, animals.link_to_subscribed_fulltex