Exploring The Electrophysiological Consequences Of Reactive Oxygen Species On Rat Papillary Muscle: Insights Into Calcium Channels And High-Energy Phosphates
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Abstract
Purpose: Oxidative stress can affect myocardial contractility. The mechanism mediating the functional change at pathophysiological concentrations of reactive oxygen species (ROS) is not well defined. Two major factors influencing myocardial contractility are – calcium (Ca) transients and availability of high-energy phosphates. Inotropic response to physiologically relevant concentrations of ROS and the role of Ca channels and availability of energy metabolites in the mediation of ROS induced inotropic changes were studied in rat heart preparations.
Procedures: Reactive oxygen species were enzymatically generated using hypoxanthine (0.5mM) and xanthine oxidase (0.02 U/ml). Changes in isometric contraction in response to ROS and the role of ion channels were studied in left ventricular papillary muscle. Effect of oxidative stress on tissue injury and energy metabolites were assessed in Langendorff perfused heart.
Findings: A negative inotropic response was seen on exposure to the free radical generator. Superoxide anions appear to modify voltage gated Ca channels and sarcoplasmic reticular Ca uptake and release. Creatine phosphate and ATP levels were significantly reduced.
Conclusion:The negative inotropic response to reactive oxygen species can be the co-ordinated response to decrease in Ca transients associated with a decrease in the energy available for contraction
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