NCX4016 (NO-aspirin) reduces infarct size and suppresses arrhythmias following myocardial ischaemia/reperfusion in pigs.
1. 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. 2. 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 A(2) from platelets activated ex vivo with A23187 (30 microM), whereas all three interventions markedly attenuated platelet aggregation in response to collagen in whole blood in comparison to controls. 3. 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). 4. 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.
Wainwright
Cherry L
CL
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow G4 0NR, Scotland, UK. c.l.wainwright@strath.ac.uk
Miller
Ashley M
AM
Work
Lorraine M
LM
Del Soldato
Piero
P
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D001241:Aspirin / Q000031:analogs & derivatives / Q000627:therapeutic use*; D003327:Coronary Disease / Q000188:drug therapy; D004730:Endothelium, Vascular / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D010974:Platelet Aggregation / Q000187:drug effects; D013552:Swine; D013929:Thromboxane B2 / Q000096:biosynthesis; D014693:Ventricular Fibrillation / Q000188:drug therapy
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013929:Thromboxane B2; C102148:nitroaspirin; D001241:Aspirin