The effect of ibuprofen on accumulation of indium-111-labeled platelets and leukocytes in experimental myocardial infarction.

Abstract

SUMMARY To assess the ability of ibuprofen to influence the extent of platelet aggregation and leukocyte infiltration during acute myocardial infarction, autologous indium-111 ("IIn)-labeled platelets or leukocytes were injected before 60 minutes of left circumflex coronary artery (LCx) occlusion, followed by 24 hours of reperfusion in the canine heart. Myocardial infarct size, as a percent of the area at risk, was reduced in the ibuprofen-treated group (12.5 mg/kg i.v. every 4 hours beginning 30 minutes before LCx occlusion) by 40%, from 48 4% in control animals to 29 4% in ibuprofen-treated dogs (p = 0.005).Quantification of the platelet-associated "l'In radioactivity in irreversibly injured myocardium indicated that ibuprofen did not alter the accumulation of platelets in infarcted myocardium. In contrast, leukocyte accumulation in infarcted tissue was reduced significantly. In tissue samples with 0.414.60 gram infarct, the in'farcted/normal ratio of leukocyte radioactivity was 12 ± 2 in control dogs and 4 + 1 in ibuprofentreated dogs, which represents a 67% reduction in leukocyte accumulation in ibuprofen-treated compared with control dogs. Similar reductions were found in other gram-infarct-weight categories. Although both platelets and leukocytes accumulate in infarcted canine myocardium, ibuprofen may exert its beneficial effect on ischemic myocardium by suppressing the inflammatory response associated with myocardial ischemia and infarction.THE GOAL of much cardiovascular research has been to develop pharmacologic means of managing patients before or soon after an acute ischemic insult to minimize the extent of irreversible myocardial injury and subsequent loss of ventricular function. Several agents are effective in reducing the extent of myocardial infarction resulting from experimentally induced acute myocardial ischemia in a variety of animal models.1 One such agent, ibuprofen, is a nonsteroidal antiinflammatory compound that has been reported to exert cardioprotective effects by significantly reducing the extent of irreversible myocardial injury to experimental ischemia in the dog,2'3 the cat,4 and the rat.5 Ibuprofen renders its cardioprotective effects administered orally,3 intravenously2 or intramuscularly.5Several independent investigators have demonstrated protective effects in a variety of experimental models of myocardial ischemia and infarction, but little is known about ibuprofen's mechanism of action. Apparently, the beneficial effects of ibuprofen do not derive from alteration of the balance of myocardial oxygen supply and demand in a favorable manner. Intravenous ibuprofen reportedly has negligible hemodynamic effects2' 6 and almost no effect on the calculated ratepressure product, an accepted approximation of myocardial oxygen consumption,7 during myocardial ischemia in the dog.6 Moreover, in the nonischemic, isolated, blood-perfused cat heart, an animal model that permits careful control of hemodynamic variables, ibuprofen did not alter myocardial oxygen consumption as measured by art...

Antibody to CD-18 exerts endothelial and cardiac protective effects in myocardial ischemia and reperfusion.

“…Additional support for the concept of neutrophil-mediated myocardial injury has been obtained in neutropenic or neutrophil blocked animals during myocardial ischemia and reperfusion (6). Other experiments show that inhibitors of 5-lipoxygenase metabolism (19), prostacyclin, or its analogues (20,21), or agents that inhibit the activation of neutrophils (21) are also effective in reducing experimental myocardial injury during reperfusion by reducing the extent of neutrophil accumulation within the previously ischemic myocardium. It is proposed that neutrophil adherence to endothelial cells is a prerequisite for deleterious effects of these leukocytes on endothelium and myocardium (22,23).…”

Interaction of Cardiovascular Risk Factors with Myocardial Ischemia/Reperfusion Injury, Preconditioning, and Postconditioning

“…Several pathological mechanisms associated with reperfusion, including ROS generation, intracellular calcium overload, and the recruitment of inflammatory cells, became the foci of basic studies in which agents were administered as adjuncts to reperfusion. Examples include the application at reperfusion of SOD (Jolly et al, 1984;Uraizee et al, 1987;Przyklenk and Kloner, 1989;Downey et al, 1991), adenosine and adenosine receptor agonists (for a comprehensive account of the early experimental literature, see Baxter et al, 2000), nonsteroidal antiinflammatory drugs (Romson et al, 1982;Mullane et al, 1984;Allan et al, 1985;Reimer et al, 1985;Crawford et al, 1988), and antineutrophil antisera (for a review, see Baxter, 2002a). The resulting literature for nearly two decades was characterized by no clear sense of experimental reproducibility or consistency of interpretation with regard to pharmacological infarct limitation.…”

Myocardial protection with preconditioning.

“…The experiments that form the basis of this report 13.0 and 20.0 kg, were anesthetized with an intravenous injection of diallyl barbituric acid and urethane (0.6 ml/kg). The animals were intubated with a cuffed endotracheal tube and ventilated with room air on a Harvard respirator (Harvard Apparatus, South Natick, Mass.)…”