Effect of cyclophosphamide on regulation of heart contractions by means of sodium calcium exchanger

Authors

DOI:

https://doi.org/10.18413/rrpharmacology.11.539

Abstract

Introduction: Every year brings in new medications capable to slow or stop proliferation of tumour cells. Unfortunately, in spite of antitumour benefits, new medicines have some side effects that reduce their therapeutic properties.

Materials and Methods: The study was conducted in three series of experiments on 24 whiteWistar rats, both male and female, each weighing 200-250 g. Decapitation of the animal was performed under ether anesthesia with rapid extraction of the heart and perfusion using the Langendorff method. To study NCX in the heart, a perfusion device was used to create a permanent coronary flow. Monitoring the physiological state of the heart when changing the composition of solutions was carried out using a balloon inserted into the left ventricle.Contractions and relaxation of the heart were recorded using an electronic pressure sensor. The parameters were documented and processed using the Zet Lab external module software.

Results and Discussion: In the first series of experiments, the effect of hyposodic solution onthe tone of the left ventricle of the heart stopped by a hyperpotassic medium was studied. The developed technique served as the basis for studying the effect of cyclophosphamide on NCX,accompanied by contraction and relaxation of the heart. Experiments have shown the ability of cyclophosphamide to significantly reduce the rate of the tone increase and the development of contraction force, as well as prolong the relaxation time during NCX.

Conclusion: Cyclophosphamide is able to disrupt the capture of ionized calcium in the cytosolby intracellular Ca-accumulating structures during relaxation of the heart. Unlike controlrecordings, in the presence of cyclophosphamide, repeated relaxations do not occur completely.As a result, each subsequent contraction begins at a higher initial diastole level.

Graphical Abstract

Keywords:

NCX, slow calcium channels, sarcoplasmic reticulum, cyclophosphamide, isolated rat’s heart contractions

References

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Author Contribution

Tatyana A. Berezhnova, Voronezh N.N. Burdenko State Medical University

Doctor Habil. of Medical Sciences, Professor, Head of the Pharmacology Department, Voronezh N.N. Burdenko State Medical University; e-mail: farmdecanat@vrngmu.ru; ORCID IDhttps://orcid.org/0000-0002-8401-3460. Author’s contribution: approval of the version of the manuscript submitted to the journal.

Ivan P. Moshurov, Voronezh N.N.Burdenko State Medical University

Doctor Habil. of Medical Sciences,  Professor, Head of the Oncology Department, Voronezh N.N.Burdenko State Medical University, Honored Doctor of the Russian Federation; e-mail: moshurov@vokod.vrn.ru; ORCID ID https://orcid.org/0000-0003-1333-5638. The author’scontribution: a significant contribution to the analysis of the data obtained.

Yang Baofeng, Co-Chairman of the Russian-Chinese Association of Medical Universities

Member of the Chinese Academy of Engineering Sciences, Professor, Co-Chairman of the Russian-Chinese Association of Medical Universities (RCAMU); e-mail: yangbf@ems.hrbmu.edu.cn; ORCID ID https://orcid.org/0000-0002-0125-1608. The author’scontribution: the revision of the manuscript.

Chaoqian Xu, Harbin Medical University

Vice President of Harbin Medical University, Professor in Pharmacology, College of Pharmacology, Harbin Medical University, Leading State and Provincial Laboratories of BiomedicalPharmaceuticals of China, Research Laboratory of Cardiovascular Medicine; e-mail:  xuchaoqian@ems.hrbmu.edu.cn; ORCID ID https://orcid.org/0009-0001-9528-7985. The author’s contribution:  the revision of the manuscript.

Irina V. Kovalenko, Voronezh N.N.Burdenko State Medical University

Assistant  of the Department of the Pharmacology Department, Voronezh N.N.Burdenko State Medical University; e-mail: kovalenkoirin@gmail.com; ORCID ID https://orcid.org/0000-0002-3094-4307. The author’s contribution: analysis of the obtained data.

Vladimir V. Alabovsky, Voronezh N.N.Burdenko State Medical University

Doctor of Medical Sciences, Professor of the Department of Clinical Laboratory Diagnostics, Voronezh N.N.Burdenko State Medical University; e-mail: v.alabovsky@yandex.ru; ORCID IDhttps://orcid.org/0000-0002-6306-5149. Author’s contribution: a significant contribution to thedevelopment of the research concept.

Alexey A. Vinokurov, Voronezh N.N.Burdenko State Medical University

Candidate of Medical Sciences, Assistant Lecturer of the Department of Clinical Laboratory Diagnostics, Voronezh N.N.Burdenko State Medical University; e-mail: alwin66@rambler.ru; ORCID ID https://orcid.org/0000-0003-0677-4739. Author’s contribution:a significant contribution to the design of the manuscript.

Oleg V. Maslov, Voronezh N.N.Burdenko State Medical University

Candidate of Biological Sciences, Associate Professor of the Department of Clinical Laboratory Diagnostics, Voronezh N.N.Burdenko State Medical University; e-mail: maslov-oleg1205@mail.ru; ORCID ID https://orcid.org/0000-0001-9476-2695. The author’scontribution: a significant contribution to the analysis of the data obtained.

Yana V. Kulintsova, Voronezh N.N.Burdenko State Medical University

Candidate of Medical Sciences, Associate Professor of the Pharmacology Department, Voronezh N.N.Burdenko State Medical University; e-mail: kulintsova@mail.ru; ORCID ID https://orcid.org/0000-0003-4569-4766. The author’s contribution: participation inwriting the draft of the manuscript.

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Published

25-02-2025

How to Cite

Berezhnova TA, Moshurov IP, Baofeng Y, Xu C, Kovalenko IV, Alabovsky VV, Vinokurov AA, Maslov OV, Kulintsova YV (2025) Effect of cyclophosphamide on regulation of heart contractions by means of sodium calcium exchanger. Research Results in Pharmacology 11(1): 1–12. https://doi.org/10.18413/rrpharmacology.11.539

Issue

Vol. 11 No. 1 (2025)

Section

Experimental Pharmacology

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Copyright (c) 2025 Татьяна А. Бережнова, Иван П. Мошуров, Ян Баофен, Чаоцянь Сюй; Ирина В. Коваленко; Владимир В. Алабовский, Алексей А. Винокуров, Олег В. Маслов, Яна В. Кулинцова

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