23 research outputs found
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
Peer reviewe
a primary source of neutron for the s-process and a major neutron poison in CEMP AGB stars
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