Reperfusion-induced arrhythmias are not prevented by ibuprofen in isolated rat heart.
Free radicals have been implicated in the genesis of reperfusion-induced arrhythmias and the cyclooxygenase pathway has been suggested as a potential source. We have therefore assessed whether a cyclooxygenase inhibitor, ibuprofen, is able to reduce reperfusion-induced injury in the isolated perfused rat heart. A duration of 10 min of regional ischemia, which resulted in a high (83%) incidence of ventricular fibrillation, was selected and hearts (n = 12/group) were perfused with ibuprofen (2, 20, or 30 mg/L) throughout the experiment. Ibuprofen did not affect heart rate, although it did produce a dose-dependent increase in coronary flow. However, at all doses studied, ibuprofen had no effect upon the time to onset, incidence, or duration of arrhythmias. In subsequent studies with 30 min of regional ischemia, ibuprofen (30 mg/L) again caused vasodilatation but without effect upon heart rate or severity of arrhythmias. In conclusion, we were unable to obtain evidence in support of the concept that cyclooxygenase activity or cyclooxygenase-derived free radicals are involved in the genesis of ischemia- and reperfusion-induced arrhythmias.
Bernier
M
M
Rayne Institute, St. Thomas' Hospital, London, U.K.
Alyea
E P
EP
Hearse
D J
DJ
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000209:etiology; D003326:Coronary Circulation / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors; D005609:Free Radicals; D006339:Heart Rate / Q000187:drug effects; D007052:Ibuprofen / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000188:drug therapy*; D051381:Rats; D011919:Rats, Inbred Strains; D015424:Reperfusion
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D005609:Free Radicals; D016718:Arachidonic Acid; D007052:Ibuprofen; D007213:Indomethacin