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.

Pigs were given aspirin (10 mg kg−1; n=6), low dose NCX4016 (18.4 mg kg−1; n=6) or high dose NCX4016 (60 mg kg−1; 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 A2 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.

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−1 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).

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.

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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