Role of a nonsteroidal anti-inflammatory agent, ibuprofen, in coronary revascularization after acute myocardial infarction

Abstract

The efficacy of using a nonsteroidal anti-inflammatory agent such as ibuprofen for the salvage of ischemic and reperfused myocardium was investigated by examining its ability to improve global and regional functions as well as to preserve high-energy phosphate compounds and inhibit creatine kinase release from an isolated in-situ pig heart subjected to 1 h of normothermic regional ischemia followed by 1 h of global hypothermic arrest and 1 h of normothermic reperfusion. Preperfusion of the heart for 15 min prior to ischemic insult with 50 microM ibuprofen failed to mitigate the myocardial reperfusion injury. Ibuprofen, however, functioned as an anti-inflammatory agent, as judged by its ability to inhibit the influx of indium-111-labeled polymorphonuclear leukocytes and chromium-51 (51Cr)-labeled platelets into the ischemic and reperfused heart. It also blocked the cyclooxygenase pathway, as evidenced by the significant reduction of 6-keto-prostaglandin F1 alpha and thromboxane B2 concentrations in the perfusate. Inhibition of cyclooxygenase resulted in increased accumulation of nonesterified fatty acids, particularly arachidonic acid, in the heart. These results suggest that although ibuprofen can inhibit polymorphonuclear leukocyte and platelet influx into the ischemic and reperfused heart, it causes further damage to the already ischemic heart by reducing prostacyclin concentration and increasing free fatty acids in the heart.

Acute Aspirin Treatment Abolishes, whereas Acute Ibuprofen Treatment Enhances Morphine-Induced Cardioprotection: Role of 12-Lipoxygenase

“…Furthermore, studies in isolated rat hearts have also shown that ibuprofen improves functional recovery (Karmazyn, 1986). However, conflicting reports have shown that ibuprofen does not improve functional recovery of isolated feline and pig hearts Clement et al, 1990). Although there is conflicting evidence suggesting that ibuprofen may not improve cardiac functional recovery, our data and those of others suggest that ibuprofen reduces infarct size in different animal models and that the cardioprotective benefits of ibuprofen likely extend to humans (Walinsky et al, 1983).…”

IL-6 and TNFα release in association with neutrophil activation after cardiopulmonary bypass surgery

“…Although the precise mechanism underlying leukocytemediated tissue damage remains unclear, experimental evidence suggests that activated neutrophils may either physically obstruct capillaries limiting reperfusion [6,7] or alternatively, mediate tissue injury through the release of secretory products which are cytotoxic to myocytes [8, 9, 9a]. Alterations in leukocyte adherence contribute to both mechanisms, as adhesion to capillaries not only promotes retention within vessels, but also promotes emigration into extravascular sites [14][15][16], phenomena which are known to occur after reperfusion of the ischaemic myocardium [17][18][19]. Neutrophil adherence also appears to trigger the release of a number of inflammatory mediators which include toxic oxygen radicals [20,21].…”