Investigation of the effect of nitrite in the management and treatment of myocardial infarction.

Abstract

Coronary heart disease is the commonest cause of death in the UK, in the main as a consequence of acute myocardial infarction (AMI)) causing 1 in 5 and 1 in 7 deaths in men and women respectively – a total of around 88,000 deaths per year. Presently, timely and effective reperfusion with primary percutaneous coronary intervention (PCI) for AMI remains the most effective treatment strategy for limiting infarct size, preserving left ventricular ejection fraction and improving clinical outcomes. However, the process of reperfusion (known as myocardial ischaemia-reperfusion (I/R) injury) can itself induce cardiomyocyte death, for which there is currently no effective therapy. A potential solution to the problem of I/R injury may exist in the form of inorganic nitrite (NO2-). Over the last decade evidence has accumulated supporting the view that nitrite, which is abundant in blood and tissues, represents a significant stable intravascular endocrine reservoir and tissue storage form of nitric oxide (NO) that exerts a number of beneficial effects. Endogenous NO generation maintains vascular tone, inhibits vascular smooth muscle contraction/growth, platelet aggregation, and leukocyte adhesion to the endothelium. However, during ischaemia the ability of the predominant isoform that underlies this NO synthesis i.e. endothelial NO synthase (eNOS) is severely attenuated as a result of inadequate delivery of oxygen and co-factors. It is clear that identification of strategies that look to restore or replace diminished NO have therapeutic potential. 6 Extensive preclinical evidence exists to suggest that nitrite (as a source of NO) is an effective therapeutic strategy for preventing myocardial I/R injury. In this project using a randomised clinical trial it was shown whether sodium nitrite reduces I/R injury and subsequent infarct size in patients undergoing primary PCI for AMI, and the mechanisms by which this may have occurred. Additionally the potential long-term benefits of nitrite supplementation post PCI were examined in-vitro models of I/R injury.