The study was designed to investigate the effect of verapamil on the speed of propagation of electrical excitation in the myocardium. As a result, it was found that verapamil reduces heart rate, the speed of excitation in the myocardium remains unchanged. The results obtained allow us to estimate the effect of verapamil on the condition of cardiac tissue, based on the change in its conductivity during treatment with the drug.
INTRODUCTION
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 diastolic depolarization in the atypical cardiomyocytes of the conduction system [1]. 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 [2]. 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.
MATERIALS 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 mol / L. For registration of the electrical activity of the myocardium multi-electrode mapping setting with flexible matrices was used. 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 detection electrode of the matrix was not changed (Fig.1).
Fig. 1. Changes in heart rate and speed of propagation of the excitation wave in the isolated rat heart under the influence of verapamil
CONCLUSIONS
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, which indicates the existence of specific mechanisms to prevent a change in the conductivity of the myocardium, causing the termination of calcium channels of L-type. The work was supported by the Russian Science Foundation (Project No. 14-12-00811).
| Attachment | Size |
|---|---|
 10.20388omp2015.00s1.009.pdf | 247.44 KB |
Echizen H., Eichelbaum M. Clinical pharmacokinetics of verapamil, nifedipine and diltiazem // Clin. Pharmacokinetics. 1986. Vol. 11, pp. 425-449;
Thimm J., Mechler F., Lin H., Rhee S., Lal R. Calcium-dependent Open/Closed Conformations and Interfacial Energy Maps of Reconstituted Hemichannels // The journal of biological chemistry. 2005. Vol. 280, No. 11, pp. 10646–1065.
