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Effects of S-Nitrosoglutathione on Electrophysiological Manifestations of Mechanoelectric Feedback

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Abstract

Electromechanical coupling studies have described the intervention of nitric oxide and S-nitrosylation processes in Ca2+ release induced by stretch, with heterogeneous findings. On the other hand, ion channel function activated by stretch is influenced by nitric oxide, and concentration-dependent biphasic effects upon several cellular functions have been described. The present study uses isolated and perfused rabbit hearts to investigate the changes in mechanoelectric feedback produced by two different concentrations of the nitric oxide carrier S-nitrosoglutathione. Epicardial multielectrodes were used to record myocardial activation at baseline and during and after left ventricular free wall stretch using an intraventricular device. Three experimental series were studied: (a) control (n = 10); (b) S-nitrosoglutathione 10 µM (n = 11); and (c) S-nitrosoglutathione 50 µM (n = 11). The changes in ventricular fibrillation (VF) pattern induced by stretch were analyzed and compared. S-nitrosoglutathione 10 µM did not modify VF at baseline, but attenuated acceleration of the arrhythmia (15.6 ± 1.7 vs. 21.3 ± 3.8 Hz; p < 0.0001) and reduction of percentile 5 of the activation intervals (42 ± 3 vs. 38 ± 4 ms; p < 0.05) induced by stretch. In contrast, at baseline using the 50 µM concentration, percentile 5 was shortened (38 ± 6 vs. 52 ± 10 ms; p < 0.005) and the complexity index increased (1.77 ± 0.18 vs. 1.27 ± 0.13; p < 0.0001). The greatest complexity indices (1.84 ± 0.17; p < 0.05) were obtained during stretch in this series. S-nitrosoglutathione 10 µM attenuates the effects of mechanoelectric feedback, while at a concentration of 50 µM the drug alters the baseline VF pattern and accentuates the increase in complexity of the arrhythmia induced by myocardial stretch.

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Abbreviations

NO:

Nitric oxide

VF:

Ventricular fibrillation

DFr:

Dominant frequency

SpC:

Spectral concentration

P5:

Fifth percentile of the activation intervals during VF

CI:

Ventricular fibrillation complexity index

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Funding

Carlos III Health Institute/FEDER funds (Spanish Ministry of Economy and Competitiveness): Grants FIS PI12/00407, PI15/01408, PIE15/00013, and RETIC “RIC” RD12/0042/0048. Generalitat Valenciana: Grant PROMETEO FASE II 2014/037.

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Authors and Affiliations

  1. Department of Physiotherapy, Universitat de València “Estudi General”, Valencia, Spain

    Luis Such-Miquel & Manuel Zarzoso

  2. Department of Medicine, Universitat de València “Estudi General”, Valencia, Spain

    Irene del Canto & Francisco J. Chorro

  3. Department of Physiology, Universitat de València “Estudi General”, Valencia, Spain

    Laia Brines, Carlos Soler, Germán Parra, Antonio Alberola & Luis Such

  4. Department of Electronic Engineering, Universitat Politècnica de València, Valencia, Spain

    Antonio Guill

  5. Department of Cardiology, Valencia University Clinic Hospital, INCLIVA, Valencia, Spain

    Francisco J. Chorro

  6. CIBER CV, Madrid, Spain

    Luis Such-Miquel, Irene del Canto, Antonio Guill, Antonio Alberola, Luis Such & Francisco J. Chorro

  7. Service of Cardiology, University Clinic Hospital, Avda. Blasco Ibañez 17, 46010, Valencia, Spain

    Francisco J. Chorro

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  1. Luis Such-Miquel
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Correspondence to Francisco J. Chorro.

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Such-Miquel, L., del Canto, I., Zarzoso, M. et al. Effects of S-Nitrosoglutathione on Electrophysiological Manifestations of Mechanoelectric Feedback. Cardiovasc Toxicol 18, 520–529 (2018). https://doi.org/10.1007/s12012-018-9463-1

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