Role of a nonsteroidal anti-inflammatory agent, ibuprofen, in coronary revascularization after acute myocardial infarction.
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.
Clement
R
R
Department of Surgery, University of Connecticut School of Medicine, Farmington.
Das
D K
DK
Engelman
R M
RM
Otani
H
H
Bandhyopadhyay
D
D
Hoory
S
S
Antar
M
M
Rousou
J A
JA
Breyer
R H
RH
Prasad
M R
MR
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D001026:Coronary Artery Bypass; D016861:Cyclooxygenase Inhibitors; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D007052:Ibuprofen / Q000008:administration & dosage*; D009203:Myocardial Infarction / Q000601:surgery*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009504:Neutrophils / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010725:Phosphocreatine / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D013552:Swine; D013929:Thromboxane B2 / Q000378:metabolism
D016861:Cyclooxygenase Inhibitors; D005230:Fatty Acids, Nonesterified; D010725:Phosphocreatine; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D000255:Adenosine Triphosphate; D007052:Ibuprofen