[Effect of different doses of aspirin on preconditioning against stunning in conscious sheep].
Non-steroid antiinflammatory drugs, inhibitors of cyclooxigenase (COX), have been postulated to have deletereous effects on the heart. Recently, COX-2 inhibitors have also been found to block late preconditioning (LP) protection. Aspirin is the most widely clinically used non-steroid antiinflammatory drug; yet its effect on LP in big mammals has not been determined. It inhibits the two cyclooxigenase isoenzymes (COX-1 and COX-2), at high doses being used as an antiinflammatory drug and at low doses as an antithrombotic agent. The goal of this study was thus, to analyse the effect of different aspirin doses on LP protection against stunning and arrhythmias in a conscious sheep model. The animals were divided in 5 groups: control (C): 12 min ischemia (I)-2 hr reperfusion (R); LP: 6 periods of 5 min I-5 min R, 24 hr before 12 min I, and three groups same as LP, but with 1.5 (LPA1.5), 8 (LPA8) and 20 (LPA20) mg/kg aspirin respectively, administered 10 min before the first preconditioning I. Results showed that the antiinflammatory dose of aspirin (20 mg/kg) was able to inhibit LP against stunning (C vs LPA20, NS), whereas low (1.5 mg/kg) and intermediate (8 mg/kg) doses did not interfere with the protection (C vs LP, LPA1.5 and LPA8, p < 0.01). Moreover, no dose altered the protection against arrhythmias.


CONCLUSIONS
Antithrombotic aspirin doses would not inhibit LP protection against stunning, whereas high antiinflammatory doses would be potentially deletereous. Since high doses of aspirin blocked LP when administered before the triggering episodes, our results show that the COX pathway might be involved as a trigger of LP against stunning.
Lascano
Elena C
EC
Departamento de Fisiología, Farmacología y Bioquímica, Universidad Favaloro, Solís 453, 1078 Buenos Aires, Argentina. lascano@favaloro.edu.ar
Del Valle
Héctor F
HF
Negroni
Jorge A
JA
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D001145:Arrhythmias, Cardiac / Q000503:physiopathology / Q000517:prevention & control; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D008297:Male; D017682:Myocardial Stunning / Q000503:physiopathology / Q000517:prevention & control*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D012756:Sheep
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010975:Platelet Aggregation Inhibitors; D001241:Aspirin