Abstract
[Figure: see text].
Highlights
Arrhythmia burden, monophasic action potentials, and beat-to-beat variability of repolarization were measured in a sheep model using the IKr inhibitor dofetilide to induce QT prolongation and arrhythmia
Perturbations to cellular Ca2+ cycling may contribute to arrhythmias in long QT syndromes by 2 mechanisms: (i) reactivation of L-type Ca2+ channel and (ii) spontaneous Ca2+ release from the sarcoplasmic reticulum (SR).[3,4,5,6]
Using a drug-induced model of QT prolongation and arrhythmia in the sheep, we found that sildenafil dramatically suppressed the occurrence of afterdepolarizations and ventricular arrhythmias in vivo, and these effects were attributable to a PKGdependent effect on Ca2+ waves and reduced SR Ca2+ content
Summary
Arrhythmia burden, monophasic action potentials, and beat-to-beat variability of repolarization were measured in a sheep model using the IKr inhibitor dofetilide to induce QT prolongation and arrhythmia. Ca2+ transients, Ca2+ waves, and SR Ca2+ content were measured in isolated ventricular myocytes. PDE5 inhibition reduced beat-to-beat variability of repolarization and suppressed afterdepolarizations, premature ventricular complexes, and torsade de pointes in vivo. Dofetilide-induced delayed afterdepolarizations and triggered action potentials were suppressed by PDE5 inhibition. A decrease in SR Ca2+ uptake, increased trans-sarcolemmal Ca2+ efflux, and reduced trans-sarcolemmal Ca2+ influx led to a reduction of SR Ca2+ content and Ca2+ wave abolition. These effects were dependent on PKG activation
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.