Isoproterenol and the genesis of reperfusion-induced arrhythmias in isolated rat heart: adrenoceptor or free radical-mediated mechanisms?
In the isolated rat heart, reperfusion-induced arrhythmias were exacerbated by isoproterenol (0.01-1.0 microM). The proarrhythmic action of isoproterenol was primarily the result of a beta 1-receptor-mediated tachycardia rather than via a free radical-mediated process, since it was prevented competitively by the beta 1-receptor antagonist metoprolol, but not by the free radical scavengers mannitol, superoxide dismutase, and catalase. If heart rate was maintained by electrical pacing, the protective action of metoprolol against the isoproterenol-induced arrhythmias was lost. At high concentrations (5 and 50 microM), metoprolol alone produced a bradycardia that was probably not related to beta 1 blockade, and this resulted in some nonspecific antiarrhythmic activity. The data provide evidence that, in this model, heart rate during ischaemia is an important determinant of reperfusion-induced arrhythmias, and that free radical formation from the oxidation of high levels of exogenous isoproterenol present at the time of reperfusion does not contribute in a major way to the detrimental action of isoproterenol.
Tosaki
A
A
Cardiovascular Research, Rayne Institute, St. Thomas' Hospital, London, U.K.
Woodward
B
B
Yamamoto
F
F
Hearse
D J
DJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology*; D002304:Cardiac Pacing, Artificial; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004562:Electrocardiography; D005609:Free Radicals; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D015425:Myocardial Reperfusion; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*; D013237:Stereoisomerism
D000975:Antioxidants; D005609:Free Radicals; D011941:Receptors, Adrenergic; D008790:Metoprolol; D007545:Isoproterenol