Protocol: does sodium nitrite administration reduce ischaemia-reperfusion injury in patients presenting with acute ST segment elevation myocardial infarction? Nitrites in acute myocardial infarction (NIAMI)

Journal of Translational Medicine

Michael P Frenneaux¹  Dana Dawson¹  Juan-Carlos Kaski⁶  Nicholas Boon⁷  Melanie Madhani²  John D Horowitz⁴  David Hildick-Smith⁸  Satnam Singh¹  Konstantin Schwarz¹  Pitt Lim⁵  Nicholas Bunce⁵  Sofia A Papadopoulo⁶  Seonaidh C Cotton³  Graeme Maclennon³  Baljit Jagpal¹  Christopher J Neil¹  Margaret Bruce¹  Nishat Siddiqi¹ 

[1] Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK;Centre for Cardiovascular Sciences College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK;Centre for Healthcare Randomised Trials (CHaRT) Health Services Research Unit, University of Aberdeen, Health Sciences Building, Foresterhill, Aberdeen AB25 2ZD, UK;Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, 28 Woodville Road, Woodville South SA 5011, Australia;Cardiology Department Atkinson Morley Wing, St Georges Healthcare NHS Trust, Blackshaw Road, London SW17 0Q, UK;Cardiovascular Sciences Research Centre, Cranmer Terrace, London SW17 0RE, UK;Centre for Cardiovascular Science, The University of Edinburgh, Chancellor's Building, 49 Little France Crescent, EdinburghEH16 4SU, UK;Brighton and Sussex University Hospitals, Cardiology Research Unit, 1 Abbey Road, Brighton BN2 1ES, UK

关键词: Cardioprotection;    Primary percutaneous coronary intervention;    Sodium nitrite;    Myocardial infarction;    Ischaemia-reperfusion-injury;   

Others  :  827570
DOI  :  10.1186/1479-5876-11-116

 received in 2013-04-28, accepted in 2013-05-01,  发布年份 2013

【 摘 要 】

Background

Whilst advances in reperfusion therapies have reduced early mortality from acute myocardial infarction, heart failure remains a common complication, and may develop very early or long after the acute event. Reperfusion itself leads to further tissue damage, a process described as ischaemia-reperfusion-injury (IRI), which contributes up to 50% of the final infarct size. In experimental models nitrite administration potently protects against IRI in several organs, including the heart. In the current study we investigate whether intravenous sodium nitrite administration immediately prior to percutaneous coronary intervention (PCI) in patients with acute ST segment elevation myocardial infarction will reduce myocardial infarct size. This is a phase II, randomised, placebo-controlled, double-blinded and multicentre trial.

Methods and outcomes

The aim of this trial is to determine whether a 5 minute systemic injection of sodium nitrite, administered immediately before opening of the infarct related artery, results in significant reduction of IRI in patients with first acute ST elevation myocardial infarction (MI). The primary clinical end point is the difference in infarct size between sodium nitrite and placebo groups measured using cardiovascular magnetic resonance imaging (CMR) performed at 6–8 days following the AMI and corrected for area at risk (AAR) using the endocardial surface area technique. Secondary end points include (i) plasma creatine kinase and Troponin I measured in blood samples taken pre-injection of the study medication and over the following 72 hours; (ii) infarct size at six months; (iii) Infarct size corrected for AAR measured at 6–8 days using T2 weighted triple inversion recovery (T2-W SPAIR or STIR) CMR imaging; (iv) Left ventricular (LV) ejection fraction measured by CMR at 6–8 days and six months following injection of the study medication; and (v) LV end systolic volume index at 6–8 days and six months.

Funding, ethics and regulatory approvals

This study is funded by a grant from the UK Medical Research Council. This protocol is approved by the Scotland A Research Ethics Committee and has also received clinical trial authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA) (EudraCT number: 2010-023571-26).

Trial registration

ClinicalTrials.gov: NCT01388504 and Current Controlled Trials: ISRCTN57596739

【 授权许可】

   
2013 Siddiqi et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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