NCX4016 (NO-aspirin) reduces infarct size and suppresses arrhythmias following myocardial ischaemia/reperfusion in pigs

Wainwright, C.L., Miller, A.M., Work, L.M. and Del Soldato, P. (2002) NCX4016 (NO-aspirin) reduces infarct size and suppresses arrhythmias following myocardial ischaemia/reperfusion in pigs. British Journal of Pharmacology, 135(8), pp. 1882-1888. (doi: 10.1038/sj.bjp.0704646)

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Publisher's URL: http://dx.doi.org/10.1038/sj.bjp.0704646

Abstract

The effect of the nitro-derivative of aspirin, NCX4016, was assessed on ischaemic ventricular arrhythmias and myocardial infarct size in anaesthetized pigs in comparison to native aspirin.<p></p> Pigs were given aspirin (10 mg kg<sup>−1</sup>; n=6), low dose NCX4016 (18.4 mg kg<sup>−1</sup>; n=6) or high dose NCX4016 (60 mg kg<sup>−1</sup>; n=7) orally for 5 days prior to coronary occlusion and reperfusion. None of the interventions had any effect on baseline haemodynamics prior to coronary occlusion in comparison to control pigs (n=9). Aspirin and high dose NCX4016 both prevented the generation of thromboxane A<sub>2</sub> from platelets activated ex vivo with A23187 (30 μM), whereas all three interventions markedly attenuated platelet aggregation in response to collagen in whole blood in comparison to controls.<p></p> None of the drug interventions had any effect on the incidence of ventricular fibrillation (VF) during myocardial ischaemia (100% in all groups). However, 60 mg kg<sup>−1</sup> NCX4016 significantly attenuated the total number of premature ventricular beats (PVB's) (62±16 vs 273±40 in control pigs; P<0.05) during the first 30 min of occlusion. The higher dose of NCX4016 also significantly reduced myocardial infarct size (22.6±3.7% of area at risk vs 53.0±2.8% of area at risk in control pigs; P<0.05).<p></p> These results suggest that the nitro-derivative of aspirin, NCX4016, is an effective antiplatelet agent, which unlike aspirin also reduces the extent of myocardial injury following ischaemia and reperfusion.<p></p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Miller, Dr Ashley and Work, Dr Lorraine
Authors: Wainwright, C.L., Miller, A.M., Work, L.M., and Del Soldato, P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:British Journal of Pharmacology
Journal Abbr.:BJP
ISSN:0007-1188
ISSN (Online):1476-5381
Published Online:02 February 2009

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