Nitro-aspirin (NCX4016) reduces brain damage induced by focal cerebral ischemia in the rat

Fredduzzi, Silva; Mariucci, Giuseppina; Tantucci, Michela; Soldato, Piero Del; Ambrosini, Maria Vittoria

doi:10.1016/s0304-3940(01)01672-x

Cited by 36 publications

(23 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In response to our request for further relevant information one author provided unpublished data. This meta-analysis is therefore based on data from 24 full papers published between 1994 and 2004 (Sharkey and Butcher, 1994;Sharkey et al, 1996;Kuroda and Siesjo, 1996;Butcher et al, 1997;Aoyama et al, 1997;Takamatsu et al, 1998Takamatsu et al, , 2001Yoshimoto and Siesjo, 1999;Kuroda et al, 1999;Toung et al, 1999;Bochelen et al, 1999;Miyazawa et al, 2000;Aronowski et al, 2000;Arii et al, 2001;McCarter et al, 2001;Ebisu et al, 2001;Fredduzzi et al, 2001;Maeda et al, 2002;Brecht et al, 2003;Furuichi et al, 2003a, b;Nito et al, 2004;Chung et al, 2004;Shichinohe et al, 2004), four abstracts Toung et al, 1997;Janelidze et al, 1999;McGregor et al, 2001) and one personal communication (J Aronowski); it represents the work of 14 independent groups, and nine of 29 publications came from groups funded directly by the Fujisawa Chemical Company, the manufacturers of FK506. Within the 29 studies, 109 comparisons (see Materials and methods for definition) were identified.…”

Section: Resultsmentioning

confidence: 99%

Systematic Review and Metaanalysis of the Efficacy of FK506 in Experimental Stroke

Macleod

O’Collins

Horky

et al. 2005

J Cereb Blood Flow Metab

161

136

View full text Add to dashboard Cite

FK506 is a candidate drug for acute stroke. For such drugs, any decision to proceed to clinical trial should be based on a full and unbiased assessment of the animal data, and consideration should be given to the limitations of those data. Such an assessment should include not only the efficacy of a drug but also the in vivo characteristics and limits to that efficacy. Here we use systematic review and meta-analysis to assess the evidence for a protective effect of FK506 in animal models of stroke. In all, 29 studies were identified describing procedures involving 1759 animals. The point estimate for the effect of FK506 was a 31.3% (95% confidence interval 27.2% to 35.4%) improvement in outcome. Efficacy was higher with ketamine anaesthesia and temporary ischaemia and was lower in rats, in animals with comorbidities, and where outcome was measured as infarct size alone. Reported study quality was modest by clinical trial standards, and efficacy was lower in high-quality studies. These findings show a substantial efficacy for FK506 in experimental stroke, but raise concerns that our estimate of effect size might be too high because of factors such as study quality and possible publication bias.

show abstract

Section: Resultsmentioning

confidence: 99%

Systematic Review and Metaanalysis of the Efficacy of FK506 in Experimental Stroke

Macleod

O’Collins

Horky

et al. 2005

J Cereb Blood Flow Metab

161

136

View full text Add to dashboard Cite

show abstract

“…58 The compound induced dose-dependent relaxation of both intact and endothelium-denuded epinephrine-precontracted arteries, 59 prevented in vivo pulmonary thromboembolism, 60 and had greater protective activity than did aspirin in a model of focal cerebral ischemia. 61 In a very recent study, NCX-4016 reduced the degree of restenosis after arterial injury in hypercholesterolemic mice, and this effect was associated with reduced VSMC proliferation and macrophage infiltration at the site of arterial injury. 62 Reduction of VSMC proliferation by NCX-4016 appears to parallel the very potent inhibitory properties of authentic NO on rat VSMC proliferation in vitro.…”

Section: Nitroaspirinsmentioning

confidence: 95%

Nitric Oxide Donors and Cardiovascular Agents Modulating the Bioactivity of Nitric Oxide

Ignarro

Napoli

Loscalzo

2002

Circulation Research

424

335

View full text Add to dashboard Cite

Abstract-Nitric oxide (NO) mediates multiple physiological and pathophysiological processes in the cardiovascular system. Pharmacological compounds that release NO have been useful tools for evaluating the pivotal role of NO in cardiovascular physiology and therapeutics. These agents constitute two broad classes of compounds, those that release NO or one of its redox congeners spontaneously and those that require enzymatic metabolism to generate NO. In addition, several commonly used cardiovascular drugs exert their beneficial action, in part, by modulating the NO pathway. Here, we review these classes of agents, summarizing their fundamental chemistry and pharmacology, and provide an overview of their cardiovascular mechanisms of action. ysfunction of the normally protective endothelium is found in several cardiovascular diseases, including atherosclerosis, hypertension, heart failure, coronary heart disease, arterial thrombotic disorders, and stroke. [1][2][3][4][5][6] Endothelial dysfunction leads to nitric oxide (NO) deficiency, 1,6 -11 which has been implicated in the underlying pathobiology of many of these disorders (NO insufficiency states). (For a detailed overview of the role of NO in cardiovascular biology and pathobiology, the reader is referred to Loscalzo and Vita. 3 ) NO insufficiency may reflect an absolute deficit of NO (synthesis), impaired availability of bioactive NO, or enhanced NO inactivation. Whatever its biochemical basis, NO insufficiency limits NO-mediated signal transduction of normal or protective physiological processes. In light of this pathobiology, replacement or augmentation of endogenous NO by exogenously administered NO donors has provided the foundation for a broad field of pharmacotherapeutics in cardiovascular medicine.Organic nitrate and nitrite esters represent a time-honored class of NO-donating agents used in cardiovascular therapeutics since the 19th century. These agents have direct vasoactive effects that have been used to treat ischemic heart disease, heart failure, and hypertension for many years. Treatment with conventional nitrate preparations is limited by their therapeutic half-life, systemic absorption with potentially adverse hemodynamic effects, and drug tolerance. 1,6 To overcome these limitations, novel NO donors that offer selective effects, a prolonged half-life, and a reduced incidence of drug tolerance have been developed. NO donors are pharmacologically active substances that spontaneously release, or are metabolized to, NO or its redox congeners. In the present article, we review our current understanding of NO-donating compounds and of cardiovascular drugs that modulate the bioactivity of endogenously produced NO. NO DonorsBecause of the limited utility of authentic NO gas in many experimental systems and the short half-life of NO in vivo, compounds that have the capacity to release NO have been widely used as therapeutic agents and as pharmacological tools to investigate the role of NO in cardiovascular physiology and pathophysiology. Several NO do...

show abstract

“…The antithrombotic activity of this nitroaspirin has also been demonstrated in vivo in a rodent model of thrombosis . Nitroaspirin also induces dose-dependent relaxation of both intact and endothelium-denuded epinephrine-precontracted arteries (Minuz et al, 1995) and has been shown to possess greater protective activity than aspirin in a model of focal cerebral ischemia (Fredduzzi et al, 2001).…”

Section: Drugs Acting Simultaneously On Nitric Oxide and Cyclooxygmentioning

confidence: 99%

Modulation of Prostaglandin Biosynthesis by Nitric Oxide and Nitric Oxide Donors

Muscoli²,

et al. 2005

View full text Add to dashboard Cite

Nitro-aspirin (NCX4016) reduces brain damage induced by focal cerebral ischemia in the rat

Cited by 36 publications

References 13 publications

Systematic Review and Metaanalysis of the Efficacy of FK506 in Experimental Stroke

Systematic Review and Metaanalysis of the Efficacy of FK506 in Experimental Stroke

Nitric Oxide Donors and Cardiovascular Agents Modulating the Bioactivity of Nitric Oxide

Modulation of Prostaglandin Biosynthesis by Nitric Oxide and Nitric Oxide Donors

Contact Info

Product

Resources

About