Differential effects of purine/xanthine oxidase on the electrophysiologic characteristics of ventricular tissues.
Oxygen free radicals (OFR) exert direct effects on the electrophysiologic properties of a variety of cardiac preparations under well-oxygenated conditions and have been implicated in the genesis of arrhythmias associated with myocardial ischemia and reperfusion. In the present study, we examined the effects of the OFR generating system, purine and xanthine oxidase, on the intracellular electrical activity of canine Purkinje fibers and papillary muscles. Purine and xanthine oxidase generated a concentration-dependent production of superoxide anion. This was accompanied by a time- and concentration-dependent depolarization of the membrane potential and shortening of the action potential duration (APD50 and APD90) in Purkinje fibers. There was no significant effect of any concentration of purine/xanthine oxidase tested on these parameters in the papillary muscles. In addition, we observed a frequency-dependent change in the sensitivity of Purkinje fibers exposed to purine/xanthine oxidase both with respect to the concentration- and time-dependent effects on APD. In the presence of 5.75 mM purine and 25 U/L xanthine oxidase, APD was significantly shortened after 10 min when the Purkinje fiber was stimulated at a basic cycle length (BCL) of 300 ms. At a BCL of 500 ms, APD did not shorten significantly until 40 min. At longer BCL (greater than 800 ms), prolonged periods of exposure were required before any significant change in APD was observed. These results suggest that OFR can alter the electrophysiologic characteristics of cardiac tissues directly and that these effects could potentially exert a proarrhythmic effect, particularly under conditions in which heart rate (HR) is elevated.
Department of Pharmacology and Toxicology, University of Western Ontario, London, Canada.
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Tsushima
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Moffat
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004285:Dogs; D004558:Electric Stimulation; D004594:Electrophysiology; D005260:Female; D005609:Free Radicals; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D011690:Purkinje Fibers / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D014969:Xanthine Oxidase / Q000494:pharmacology*
D005609:Free Radicals; D013481:Superoxides; D014969:Xanthine Oxidase