Coronary and systemic hemodynamic effects of the new sino-atrial inhibitor, S16257, In resting and exercised conscious dogs

Simon, Lourenço; Ghaleh, Bijan; Puybasset, Louis; Giudicelli, J.; Berdeaux, Alain

doi:10.1016/1043-6618(95)86372-9

Cited by 62 publications

(104 citation statements)

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“…This is consistent with the lack of negative inotropic effect of this drug reported in other animal species as well as in humans (Simon et al, 1995;Thollon et al, 1997;Monnet et al, 2001;Colin et al, 2002). Further, this study has provided evidence that ivabradine reduces HR well under conditions where HR is elevated by sympathoadrenergic activation.…”

Section: X-j Du Et Alsupporting

confidence: 91%

“…Despite a marked HR-lowering activity of ivabradine, studies in other species have shown that this drug does not have any negative inotropic effect (Gardiner et al, 1995;Simon et al, 1995;Colin et al, 2002). In the present study, this was found to be the case in the mouse, as estimated from an unchanged FS and wall thickening under various conditions.…”

Section: X-j Du Et Alcontrasting

confidence: 72%

“…Previous studies have established the selective HR-reducing activity of ivabradine devoid of negative inotropic effect in various species, including the rat, pig, dog and human, when given intravenously (Thollon et al, 1994;Simon et al, 1995;Monnet et al, 2001;Colin et al, 2002;Camm & Lau, 2003) or orally (Borer et al, 2003). Antianginal and anti-ischaemic effects of ivabradine have been demonstrated in patients with stable angina (Borer et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…Antianginal and anti-ischaemic effects of ivabradine have been demonstrated in patients with stable angina (Borer et al, 2003). Although ivabradine is able to reduce HR under conditions of exercise (Simon et al, 1995;Monnet et al, 2001;Colin et al, 2002;Borer et al, 2003), there has been limited information on the efficacy of ivabradine in HR reduction under other conditions of enhanced sympathoadrenergic activity, a situation commonly seen under diseased conditions. In this study, we have investigated the effects of oral ivabradine on HR in the mouse with enhanced sympathoadrenergic activity due to (1) stress-evoked sympathetic activation, (2) cardiac specific overexpression of b 2 AR and (3) b-agonist stimulation.…”

Section: Introductionmentioning

confidence: 99%

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I_f channel inhibitor ivabradine lowers heart rate in mice with enhanced sympathoadrenergic activities

Gao

et al. 2004

British J Pharmacology

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1 Ivabradine selectively reduces heart rate (HR) by inhibiting the cardiac pacemaker I f current, thus prolonging the duration of spontaneous depolarization in the sinus node. The activity of ivabradine under conditions of enhanced sympathoadrenergic activity has been addressed by investigating the effects of repeated oral administration in mice with sympathoadrenergic activation due to either stress, cardiac-restricted overexpression of b 2 -adrenergic receptors (b 2 AR), or b-agonist administration. HR and left ventricular fractional shortening (FS) were determined by echocardiography.2 Initial experiments showed that the conscious restrained state was associated with stress-mediated sympathetic activation, while sympathetic withdrawal occurred under anaesthetized conditions. In wild-type mice, ivabradine reduced HR under both conscious and anaesthetized states, with a similar degree in absolute reduction under both states. FS was unchanged by the treatment. 3 Ivabradine was similarly effective in reducing HR in the b 2 AR transgenic mice. Further, ivabradine at 10 mg kg À1 day À1 reduced the maximal HR increase in response to the b-agonist isoproterenol, without modifying the response of contractile parameters. 4 These data indicate that oral administration of ivabradine in mice reduces HR while ventricular performance is maintained. This specific HR-reducing action of ivabradine is well preserved under conditions that are associated with significant activation of the sympathoadrenergic system.

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Section: X-j Du Et Alsupporting

confidence: 91%

Section: X-j Du Et Alcontrasting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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I_f channel inhibitor ivabradine lowers heart rate in mice with enhanced sympathoadrenergic activities

Gao

et al. 2004

British J Pharmacology

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“…reduction in heart rate is similar to that with β-blockers, but with maintenance of coronary dilatation during exercise 46 . In addition, ivabradine increases coronary flow reserve and collateral perfusion, promoting the development of coronary collaterals and maintaining endothelial function in patients with chronic stable angina 47,48 .…”

Section: Key Points For Nicorandilsupporting

confidence: 52%

A 'diamond' approach to personalized treatment of angina

et al. 2017

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Chronic stable angina pectoris is the most prevalent symptomatic manifestation of ischaemic heart disease, and its management is a priority (BOX 1). Current clinical guidelines recommend antianginal therapy to control symptoms, before considering coronary artery revasculariza tion [1][2][3][4] . However, revascularization by either percutaneous coronary angioplasty or CABG surgery is indicated in patients who have significant artery steno sis (50% left main narrowing or proximal three-vessel disease) to reduce myocardial ischaemia and its adverse clinical manifestation. Antianginal agents are approved by documenting that they improve total exercise duration, together with a reduction in daily frequency of chronic stable angina compared with placebo and/or equivalence to an active comparator. Cardiovascular outcomes, although highly advocated, are not a pre requisite for regulatory approval. None of the antianginal drugs has been proved to reduce cardiovascular mortality or the rate of myocardial infarction. When patients are optimally treated, mortality for chronic stable angina is low, which might explain why all trials designed to improve prognosis have been negative. Guidelines recom mend a first-choice and a second-choice approach, based more on tradition and expert opinion, rather than evidence. This categorical approach has been questioned in the past couple of years 5-8 . Newer antianginal drugs, which are classified as second choice, have more evidence-based clinical data that are more contemporary to support their use than is available for the traditional first-choice drugs. Equally, the often-needed combin ation of double or triple therapy is based on expert opinion and not related to the underlying pathophysio logy. What constitutes optimal antianginal treatment, therefore, varies considerably between countries, and the majority of doctors treat their patients according to their own preconceptions.A group of experts with experience and interest in chronic stable angina met at the University of Ferrara, Italy, to discuss an individualized approach to medical treatment of chronic stable angina, on the basis E X P E RT C O N S E N S U S D O C U M E N TA 'diamond' approach to personalized treatment of angina Abstract | In clinical guidelines, drugs for symptomatic angina are classified as being first choice (β-blockers, calcium-channel blockers, short-acting nitrates) or second choice (ivabradine, nicorandil, ranolazine, trimetazidine), with the recommendation to reserve second-choice medications for patients who have contraindications to first-choice agents, do not tolerate them, or remain symptomatic. No direct comparisons between first-choice and second-choice treatments have demonstrated the superiority of one group of drugs over the other. Meta-analyses show that all antianginal drugs have similar efficacy in reducing symptoms, but provide no evidence for improvement in survival. The newer, second-choice drugs have more evidence-based clinical data that are more contemporary than is available for tr...

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Linked biaromatic compounds as cardioprotective agents

Mokrov

2021

Archiv der Pharmazie

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Cardiovascular diseases (CVDs) are widespread in the modern world, and their number is constantly growing. For a long time, CVDs have been the leading cause of morbidity and mortality worldwide. Drugs for the treatment of CVD have been developed almost since the beginning of the 20th century, and a large number of effective cardioprotective agents of various classes have been created. Nevertheless, the need for the design and development of new safe drugs for the treatment of CVD remains. Literature data indicate that a huge number of cardioprotective agents of various generations and mechanisms correspond to a single generalized pharmacophore model containing two aromatic nuclei linked by a linear linker. In this regard, we put forward a concept for the design of a new generation of cardioprotective agents with a multitarget mechanism of action within the indicated pharmacophore model. This review is devoted to a generalization of the currently known compounds with cardioprotective properties and corresponding to the pharmacophore model of biaromatic compounds linked by a linear linker. Particular attention is paid to the history of the creation of these drugs, approaches to their design, and analysis of the structure-action relationship within each class.

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Coronary and systemic hemodynamic effects of the new sino-atrial inhibitor, S16257, In resting and exercised conscious dogs

Cited by 62 publications

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I_f channel inhibitor ivabradine lowers heart rate in mice with enhanced sympathoadrenergic activities

I_f channel inhibitor ivabradine lowers heart rate in mice with enhanced sympathoadrenergic activities

A 'diamond' approach to personalized treatment of angina

Linked biaromatic compounds as cardioprotective agents

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Coronary and systemic hemodynamic effects of the new sino-atrial inhibitor, S16257, In resting and exercised conscious dogs

Cited by 62 publications

References 0 publications

If channel inhibitor ivabradine lowers heart rate in mice with enhanced sympathoadrenergic activities

If channel inhibitor ivabradine lowers heart rate in mice with enhanced sympathoadrenergic activities

A 'diamond' approach to personalized treatment of angina

Linked biaromatic compounds as cardioprotective agents

Contact Info

Product

Resources

About

I_f channel inhibitor ivabradine lowers heart rate in mice with enhanced sympathoadrenergic activities

I_f channel inhibitor ivabradine lowers heart rate in mice with enhanced sympathoadrenergic activities