<abstract xmlns="http://www.w3.org/1999/xhtml">

<sec><h3>Objective</h3><p>The sodium/calcium exchanger (NCX) and the L-type Ca<sup>2+</sup>-channel (LTCC) are nowadays considered the major transmembrane transport mechanisms that control Ca<sup>2+</sup> homeostasis. In pathophysiological conditions the altered function of these currents may influence the Ca<sup>2+</sup> homeostasis and cardiac contractility and thereby, may enhance the development of severe tachyarrhythmias. The blockade of NCX current has been proposed as possible approach in the prevention and/or suppression of arrhythmias; however, this mechanism is not always favourable because the inhibition of both modes of NCX may induce Ca<sup>2+</sup>-overload. The decrease of the Ca<sup>2+</sup> level by partial LTCC inhibition may be beneficial in increasing the antiarrhythmic efficacy. Therefore, the aim of our study was to investigate the antiarrhythmic effects of combined NCX and LTCC blockade in the <italic>ex vivo</italic> guinea pig arrhythmia model.</p></sec>
<sec><h3>Methods</h3><p>We have performed Langendorff experiments in isolated guinea pig hearts. We have recorded electrocardiograms (ECG) and left ventricle pressure. We have applied 1 μM ORM-10962 (ORM), a compound that block NCX current and 30 nM nisoldipine for the inhibition of LTCC. Arrhythmias have been provoked by decreasing the activity of the sodium/potassium pump with 5 μM ouabain.</p></sec>
<sec><h3>Results</h3><p>We found that neither LTCC nor NCX blockade alone increased, while the combined inhibition of the two currents significantly delayed (p&lt;0.05) the mean time of appearance of ouabain-induced ventricular fibrillation. The heart frequency was affected by none of the drugs, only the left ventricular pressure (end-systolic and diastolic difference) was significantly elevated by ORM (p&lt;0.001).</p></sec>
<sec><h3>Conclusion</h3><p>In the Langendorff-perfused guinea pig heart, specific, combined NCX and LTCC blockade may be favourable than the inhibition of NCX or LTCC alone. However, further investigations are necessary to identify the pathological settings in which this combined cardiac drug therapy may be a potential new approach.</p></sec>
</abstract>

ObjectiveThe sodium/calcium exchanger (NCX) and the L-type Ca2+-channel (LTCC) are nowadays considered the major transmembrane transport mechanisms that control Ca2+ homeostasis. In pathophysiological conditions the altered function of these currents may influence the Ca2+ homeostasis and cardiac contractility and thereby, may enhance the development of severe tachyarrhythmias. The blockade of NCX current has been proposed as possible approach in the prevention and/or suppression of arrhythmias; however, this mechanism is not always favourable because the inhibition of both modes of NCX may induce Ca2+-overload. The decrease of the Ca2+ level by partial LTCC inhibition may be beneficial in increasing the antiarrhythmic efficacy. Therefore, the aim of our study was to investigate the antiarrhythmic effects of combined NCX and LTCC blockade in the ex vivo guinea pig arrhythmia model.
MethodsWe have performed Langendorff experiments in isolated guinea pig hearts. We have recorded electrocardiograms (ECG) and left ventricle pressure. We have applied 1 μM ORM-10962 (ORM), a compound that block NCX current and 30 nM nisoldipine for the inhibition of LTCC. Arrhythmias have been provoked by decreasing the activity of the sodium/potassium pump with 5 μM ouabain.
ResultsWe found that neither LTCC nor NCX blockade alone increased, while the combined inhibition of the two currents significantly delayed (p<0.05) the mean time of appearance of ouabain-induced ventricular fibrillation. The heart frequency was affected by none of the drugs, only the left ventricular pressure (end-systolic and diastolic difference) was significantly elevated by ORM (p<0.001).
ConclusionIn the Langendorff-perfused guinea pig heart, specific, combined NCX and LTCC blockade may be favourable than the inhibition of NCX or LTCC alone. However, further investigations are necessary to identify the pathological settings in which this combined cardiac drug therapy may be a potential new approach.

The Investigation of Combined Na<sup>+</sup>/Ca<sup>2+</sup> Exchanger and the L-type Ca<sup>2+</sup>- Channel Inhibition in Langendorff-Perfused Isolated Guinea Pig Hearts

Department of Pharmacology and Pharmacotherapy

ELKH-SZTE Research Group for Cardiovascular Pharmacology, Eötvös Loránd Research Network

Department of Pharmacology and Pharmacotherapy, Interdisciplinary Excellence Centre

Romanian Journal of Cardiology

This work is licensed under the Creative Commons Attribution 4.0 International License.

The Investigation of Combined Na/Ca Exchanger and the L-type Ca- Channel Inhibition in Langendorff-Perfused Isolated Guinea Pig Hearts

ObjectiveThe sodium/calcium exchanger (NCX) and the L-type Ca2+-channel (LTCC) are nowadays considered the major transmembrane transport mechanisms that...

The Investigation of Combined Na⁺/Ca²⁺ Exchanger and the L-type Ca²⁺- Channel Inhibition in Langendorff-Perfused Isolated Guinea Pig Hearts

Article Category: Original Article

Publicado en línea: 05 may 2022

Páginas: 537 - 545

DOI: https://doi.org/10.47803/rjc.2021.31.3.537

Palabras clave
Langendorff-perfused hearts, guinea pig, NCX current, L-type calcium current, antiarrhythmic effect

© 2021 János Prorok et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

The Investigation of Combined Na+/Ca2+ Exchanger and the L-type Ca2+- Channel Inhibition in Langendorff-Perfused Isolated Guinea Pig Hearts

Article Category: Original Article

Publicado en línea: 05 may 2022

Páginas: 537 - 545

DOI: https://doi.org/10.47803/rjc.2021.31.3.537

Palabras claveLangendorff-perfused hearts, guinea pig, NCX current, L-type calcium current, antiarrhythmic effect

© 2021 János Prorok et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

The Investigation of Combined Na⁺/Ca²⁺ Exchanger and the L-type Ca²⁺- Channel Inhibition in Langendorff-Perfused Isolated Guinea Pig Hearts

Palabras clave
Langendorff-perfused hearts, guinea pig, NCX current, L-type calcium current, antiarrhythmic effect