title: Nonsteroidal antiinflammatory drugs aggravate acute myocardial ischemia in the perfused rabbit heart: a role for prostacyclin.
abstract: Myocardial ischemia was induced in perfused paced isovolumic left heart preparation of the rabbit by reducing, for a period of 40 min, the flow rate from 20 ml/min to 0.2 ml/min (severe model) and to 1 ml/min (moderate model). The relationship between prostaglandin biosynthesis and cardiac ischemic damage was evaluated in the two experimental models. The results obtained indicate that the total amount of 6-keto-PGF1 alpha generated increases with the severity of the ischemia, particularly during the 20 min of reperfusion (moderate model 81.8 +/- 13.7 ng: severe model 375 +/- 102 ng). The inhibition of the prostaglandin synthesis, prostaglandin-E2, and 6-keto-prostaglandin-F1 alpha (PGE2 and 6-keto-PGF1 alpha levels below the detection limits) by Aspirin (20 micrograms/ml) and Indomethacin (1 microgram/ml) in moderate myocardial ischemia was correlated with greater increments in resting diastolic tension (nearly 100% and 40%, respectively). This phenomenon was also associated to a further decrease on cardiac contractility and increase on coronary perfusion pressure upon reperfusion. On the contrary drugs which stimulated prostaglandin generation in myocardial tissue, such as Defibrotide (400 micrograms/ml), completely protected the organ from ischemia. U-60257 (3 micrograms/ml) and FPL-55712 (2 micrograms/ml), compounds, which respectively inhibits biosynthesis and the effects of leukotrienes, displayed a beneficial activity on this moderate model of ischemia. The present data suggests that the deleterious effect of nonsteroidal antiinflammatory drugs in low flow myocardial ischemia and reperfusion damage may be associated with removal of PGI2 and PGE2 from ischemic myocardium.
authors: Institute of Pharmacological Sciences, University of Milan, Italy.
authors: F
authors: F
authors: Berti
authors: G
authors: G
authors: Rossoni
authors: F
authors: F
authors: Magni
authors: D
authors: D
authors: Caruso
authors: C
authors: C
authors: Omini
authors: L
authors: L
authors: Puglisi
authors: G
authors: G
authors: Galli
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D003327:Coronary Disease / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D011464:Epoprostenol / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D010477:Perfusion; D011453:Prostaglandins / Q000378:metabolism; D011817:Rabbits; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011453:Prostaglandins; D011464:Epoprostenol