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Lidocaine interactions with exogenous and endogenous adenosine in the isolated rat heart
1Department of Pharmacology and Toxicology, University of Trondheim, Norway.
Abstract:
We examined whether pretreatment with lidocaine could influence the cardiac kinetics of adenosine and thereby strengthen the physiologic responses of the nucleoside, either exogenously administered or endogenously produced. Isolated rat hearts perfused with lidocaine, 0.05 microM to 500 microM, were subjected to 6 min. of adenosine infusion followed by 30 min. of perfusion. The hearts were then subjected to 6 min. of total global ischaemia and then perfused for 30 min. Effects on cardiac kinetics and physiologic responses of adenosine were based on a comparison of uptake or release of adenosine in effluate (kinetics), and the effects of adenosine on aortic pressure and left ventricular developed pressure (physiologic responses), to a lidocaine-free control group. A low concentration of lidocaine, 0.05 microM, increased the uptake of exogenously administered adenosine. A high concentration of lidocaine, 50 and 500 microM was associated with a reduced release of endogenously produced adenosine. However, these effects on cardiac kinetics of adenosine were not associated with any increase of the physiologic responses to the nucleoside. The results failed to support the hypothesis that lidocaine increases the physiologic responses of adenosine in the isolated rat heart by a kinetic interaction.
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