Effect Of Verapamil On a Speed Of The Excitation Wave Conduction In The Isolated Rat Heart Myocardium

Abstract

Event Abstract Back to Event Effect Of Verapamil On a Speed Of The Excitation Wave Conduction In The Isolated Rat Heart Myocardium Elena Kharkovskaia1*, Natalya Zhidkova2, Evgeniya Arkhipova3, Natalia Shchelchkova4, G. V. Osipov1 and Irina Mukhina1, 4 1 Lobachevsky State University, Russia 2 Lobachevsky State University, Russia 3 Nizhny Novgorod State Medical Academy, Russia 4 Nizhny Novgorod State Medical Academy, Russia Motivation Calcium antagonists are widely used in the treatment and prevention of heart diseases. Verapamil is a blocker of the slow L-type calcium channel. The action of verapamil in the heart accompanied by negative inotropic and chronotropic effects, since the restriction of entry of calcium ions leads to a quantifiable reduction in the formation of actin-myosin bonds in the working cardiomyocytes and to inhibition of spontaneous depolarization in the atypical cardiomyocytes of the conduction system. The concentration of calcium ions also affect the speed of propagation of a wave of electrical excitation due to the regulation of connexons, which is placed in the intercalated discs of cardiomyocytes. The aim of the study was to examine the effect of verapamil on the speed of propagation of the excitation wave in the ventricular myocardium of isolated rat heart with using FlexMEA72 (Multichannel Systems). Additionally, a comparison between speed values obtained under the influence of verapamil in normal conditions and under the influence of verapamil in the condition of hypoxia was carried out. Material and Methods Isolated hearts of outbred white rats were perfused by the Langendorff method. After 10 minutes of perfusion with Krebs-Henseleit solution (NaCl 118, KCl 4,7, CaCl2 2, MgSO4 1,2, KH2PO4 1,2, NaHCO3 20, glucose 10 mkmol/L) in an experimental group perfusion was held with addition of verapamil with a concentration of 7 mkmol / L. The condition of hypoxia was simulated by stopping delivery of carbogen to perfusion solution. The presence of hypoxia in the myocardium was verified by biochemical analysis evaluating the ratio of lactate/pyruvate. For registration of the electrical activity of the myocardium multi-electrode mapping setting with flexible matrices FlexMEA72 (Multichannel Systems) was used. The data were analyzed in the Cardio2D+ Software. Heart rate measured by the number of heart beats per minute. The speed of propagation of the wave excitation of the heart was calculated based on the difference between the values of time of occurrence of electrical potentials recorded by the electrodes of the matrix. Comparison of the average values of obtained parameters at different stages of the experiment, as well as a comparison of these values in the control and experimental groups, was performed by Student t-test for dependent samples. Differences were considered significant at a significance level of p <0.05. Results As a result of the study it was found that during the perfusion of the isolated rat heart with a solution containing verapamil heart rate decreased to 1.52 times compare with the control group. The velocity of propagation of excitation between the electrodes of the matrix was not changed. In hypoxic conditions with verapamil treatment velocity value increased to 1.8 times. Without verapamil hypoxia caused the velocity reducing to 1.4 times. Discussion The study was designed to investigate the effect of verapamil on the speed of propagation of electrical excitation in the myocardium under the normal conditions and under hypoxia and influence of verapamil simultaneously. To achieve this goal the Flexible microelectrode array «FlexMEA72» (Multichannel Systems) were used. Spatial and temporal resolution of arrays allowed to register the electrical excitation wave passing through the myocardium of the left ventricle and to evaluate its speed. The obtained results made it possible to estimate the effect of verapamil on the condition of cardiac tissue, based on the change in its conductivity during treatment with the drug. It was found that verapamil reduces heart rate, but the speed of excitation spreading in the myocardium remains unchanged. In case of hypoxia conductive velocity value decreased because of disruption of normal metabolism in cardiomyocytes. In the presence of verapamil effect of hypoxia expressed in increase of the speed of electrical wave propagation. Calcium influx leads to activation of myofibrillar adenosine triphosphatase which converts phosphate bound energy into mechanical work: thus calcium influx is an important determinant of myocardial oxygen consumption. Verapamil therefore, by limiting calcium influx, reduce calcium-dependent splitting of adenosine triphosphate, which in turn reduces myocardial oxygen demand and in this way can influence on the velocity by regulation of calcium concentration. Moreover, verapamil by helping to reduce energy consumption in the cells of the myocardium in some way produce increasing of conductive velocity, possibly by activating certain mechanisms aimed at restoring normal electrical conductivity. Conclusion Perfusion with a solution containing verapamil influenced on the calcium dynamics in myocardium of the isolated rat hearts that was expressed in a negative chronotropic effect. But this influence did not cause changes in the speed of propagation of the wave of excitation along the surface of the myocardium in normal conditions. It features the existence of specific mechanisms to prevent a change in the conductivity of the myocardium, causing the termination of calcium channels of L-type. But the presence of verapamil caused a negative chronotropic effect, indicating thereby suppression of sinus node activity. On the other hand, it was found that in the presence of verapamil in the perfusion solution hypoxia enhances electrical conductivity of the myocardium of the isolated heart. Thus, through the use of flexible multi-electrode arrays restoring effect of verapamil on the state of the myocardium during hypoxia was shown. Acknowledgements This research was supported by the Russian Science Foundation (Contract #14-12-00811). Keywords: Verapamil, L-type calcium channel, Isolated rat heart, excitation wave propagation, FlexMEA72, the conduction system Conference: MEA Meeting 2016 | 10th International Meeting on Substrate-Integrated Electrode Arrays, Reutlingen, Germany, 28 Jun - 1 Jul, 2016. Presentation Type: oral Topic: MEA Meeting 2016 Citation: Kharkovskaia E, Zhidkova N, Arkhipova E, Shchelchkova N, Osipov GV and Mukhina I (2016). Effect Of Verapamil On a Speed Of The Excitation Wave Conduction In The Isolated Rat Heart Myocardium. Front. Neurosci. Conference Abstract: MEA Meeting 2016 | 10th International Meeting on Substrate-Integrated Electrode Arrays. doi: 10.3389/conf.fnins.2016.93.00023 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 22 Jun 2016; Published Online: 24 Jun 2016. * Correspondence: Dr. Elena Kharkovskaia, Lobachevsky State University, Nizhni Novgorod, Russia, elharkov@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Elena Kharkovskaia Natalya Zhidkova Evgeniya Arkhipova Natalia Shchelchkova G. V Osipov Irina Mukhina Google Elena Kharkovskaia Natalya Zhidkova Evgeniya Arkhipova Natalia Shchelchkova G. V Osipov Irina Mukhina Google Scholar Elena Kharkovskaia Natalya Zhidkova Evgeniya Arkhipova Natalia Shchelchkova G. V Osipov Irina Mukhina PubMed Elena Kharkovskaia Natalya Zhidkova Evgeniya Arkhipova Natalia Shchelchkova G. V Osipov Irina Mukhina Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. 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