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Br J Pharmacol ; 1 :Sep. The aim of this study was to analyse the effects of eliprodil, a can type 2 diabetes cause tachycardia drug with neuroprotective properties, on the cardiac repolarisation under in vitro circumstances, under normal conditions and after the attenuation of the 'repolarisation reserve' by blocking the inward rectifier potassium current I K1 current with BaCl 2.
In canine right ventricular papillary muscle by applying the conventional microelectrode technique, under normal conditions, eliprodil 1 microm produced a moderate reverse rate-dependent prolongation of the action potential duration 7. This effect was augmented in preparations where I K1 was previously blocked by BaCl 2 10 microm.
BaCl 2 alone lengthened APD in a reverse frequency-dependent manner 7. When eliprodil 1 microm was administered to these preparations, the drug induced a marked further lengthening relative to the APD values measured after the administration of BaCl 2 In the normal Langendorff-perfused rabbit heart, eliprodil 1 microm produced a significant QT c prolongation at 1 Hz stimulation frequency After the attenuation of the 'repolarisation reserve' by the I K1 blocker BaCl 2 10 micromthe eliprodil-evoked QT c prolongation was greatly enhanced In two out of six Langendorff preparations, this QT c lengthening degenerated into torsade de pointes ventricular tachycardia.
Eliprodil significantly decreased the amplitude of rapid component of the delayed rectifier potassium current I Krbut slow component I Kstransient outward current I to and I K1 were not considerably affected by the drug when measured in dog ventricular myocytes by applying the whole-cell configuration of the patch-clamp technique.
The results indicate that eliprodil, under normal conditions, moderately lengthens cardiac repolarisation by inhibition of I Kr. However, after the attenuation of the normal 'repolarisation reserve', this drug can induce marked QT interval prolongation, which may result in proarrhythmic action.
