Date of Award


Degree Type


Degree Name

Doctor of Philosophy


Reactive oxygen species have been implicated in the development of a variety pathological conditions, including myocardial ischemia and reperfusion injury. The present study examined the effects of reactive oxygen species on the functional and electrophysiological responses of cardiac tissues.;Purine/xanthine oxidase and hydrogen peroxide (H{dollar}\sb2{dollar}O{dollar}\sb2{dollar}) caused a concentration-dependent decline in contractile force with a concomitant rise in resting tension in isolated guinea pig hearts. These observations indicate that exogenous reactive oxygen species can cause direct myocardial dysfunction in a concentration-dependent manner.;In addition, purine/xanthine oxidase significantly depressed recovery of contractile function, enhanced resting tension and prolonged the duration of reperfusion arrhythmias. In contrast, hearts reperfused with a subtoxic concentration of H{dollar}\sb2{dollar}O{dollar}\sb2{dollar} recovered better than control hearts. These results suggest that reactive oxygen species can either exacerbate or ameliorate the response of hearts to ischemia/reperfusion dependent on the type of reactive oxygen species present.;Purine/xanthine oxidase and H{dollar}\sb2{dollar}O{dollar}\sb2{dollar} elicited a time- and concentration-dependent depolarization of the membrane potential in canine Purkinje fibres. Purine/xanthine oxidase shortened the action potential duration (APD) in canine Purkinje fibres. There was a frequency-dependent change in the sensitivity of APD to purine/xanthine oxidase. Hydrogen peroxide exerted a biphasic effect on APD of the Purkinje fibres, with an initial prolongation followed by a shortening. H{dollar}\sb2{dollar}O{dollar}\sb2{dollar}was arrhythmogenic in the Purkinje fibres. There was little or no effect of purine/xanthine oxidase or H{dollar}\sb2{dollar}O{dollar}\sb2{dollar} on the papillary muscles. This study demonstrates direct and differential effects of reactive oxygen species on the electrophysiological characteristics of canine Purkinje fibres and papillary muscles. In postischemic canine Purkinje fibres, the presence of a subtoxic concentration of H{dollar}\sb2{dollar}O{dollar}\sb2{dollar} resulted in a marked depolarization of the membrane potential and the loss of excitability.;In conclusion, reactive oxygen species can have deleterious effects on cardiac tissues in the presence and absence of ischemia and reperfusion. Generation of reactive oxygen species in the postischemic myocardium may be an important factor contributing to contractile dysfunction and genesis of severe arrhythmias.



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