Diclofenac Prolongs Repolarization in Ventricular Muscle with Impaired Repolarization Reserve

Background: The aim of the present work was to characterize the electrophysiological effects of the non-steroidal anti- inflammatory drug diclofenac and to study the possible proarrhythmic potency of the drug in ventricular muscle. Methods: Ion currents were recorded using voltage clamp technique in canine single ventricular cells and action potentials were obtained from canine ventricular preparations using microelectrodes. The proarrhythmic potency of the drug was investigated in an anaesthetized rabbit proarrhythmia model. Results: Action potentials were slightly lengthened in ventricular muscle but were shortened in Purkinje fibers by diclofenac (20 mM). The maximum upstroke velocity was decreased in both preparations. Larger repolarization prolongation was observed when repolarization reserve was impaired by previous BaCl 2 application. Diclofenac (3 mg/kg) did not prolong while dofetilide (25 mg/kg) significantly lengthened the QT c interval in anaesthetized rabbits. The addition of diclofenac following reduction of repolarization reserve by dofetilide further prolonged QT c . Diclofenac alone did not induce Torsades de Pointes ventricular tachycardia (TdP) while TdP incidence following dofetilide was 20%. However, the combination of diclofenac and dofetilide significantly increased TdP incidence (62%). In single ventricular cells diclofenac (30 mM) decreased the amplitude of rapid (I Kr ) and slow (I Ks ) delayed rectifier currents thereby attenuating repolarization reserve. L-type calcium current (I Ca ) was slightly diminished, but the transient outward (I to ) and inward rectifier (I K1 ) potassium currents were not influenced. Conclusions: Diclofenac at therapeutic concentrations and even at high dose does not prolong repolarization markedly and does not increase the risk of arrhythmia in normal heart. However, high dose diclofenac treatment may lengthen repolarization and enhance proarrhythmic risk in hearts with reduced repolarization reserve

Evolution, nucleosynthesis and yields of low mass AGB stars

The envelope of thermally pulsing AGB stars undergoing periodic third dredge-up episodes is enriched in both light and heavy elements, the ashes of a complex internal nucleosynthesis involving p, alpha and n captures over hundreds of stable and unstable isotopes. In this paper, new models of low-mass AGB stars (2 Msun), with metallicity ranging between Z=0.0138 (the solar one) and Z=0.0001, are presented. Main features are: i) a full nuclear network (from H to Bi) coupled to the stellar evolution code, ii) a mass loss-period-luminosity relation, based on available data for long period variables, and ii) molecular and atomic opacities for C- and/or N-enhanced mixtures, appropriate for the chemical modifications of the envelope caused by the third dredge up. For each model a detailed description of the physical and chemical evolution is presented; moreover, we present a uniform set of yields, comprehensive of all chemical species (from hydrogen to bismuth). The main nucleosynthesis site is the thin 13C pocket, which forms in the core-envelope transition region after each third dredge up episode. The formation of this 13C pockets is the principal by-product of the introduction of a new algorithm, which shapes the velocity profile of convective elements at the inner border of the convective envelope: both the physical grounds and the calibration of the algorithm are discussed in detail. The final surface compositions of the various models reflect the differences in the initial iron-seed content and in the physical structure of AGB stars belonging to different stellar populations. The agreement with the observed [hs/ls] index observed in intrinsic C stars at different [Fe/H] is generally good.Comment: Accepted for publication on Ap

Lead and s-process elements in stars of various metallicities : AGB predictions and observations

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