ИСТИНА

Introduction. In adult mammals, including humans and rodents, the heart rhythm is maintained by the primary pacemaker – sinoatrial node (SAN), that is located at the junction of the superior caval vein (CV) and the right atrium. CV contain myocardial tissue that it is present here at all stages of ontogenesis. CV and SAN myocardium shares the same precursors, that have pacemaker properties. It was shown that during early stages of development the level of transcriptional factors that determine electrophysiological phenotype changes in CV myocardium. However, it is not clear how CV myocardium electrophysiological properties change at the same time. Purpose. The aim of this project is to investigate the CV pacemaker properties during the early postnatal ontogenesis. Methods. All the experiments were performed in accordance with the "Principles of laboratory animal care" (NIH Publication no. 85-23 revised 1985). The experiments were carried out on isolated Tyrode perfused preparations of CV with the usage of standard microelectrode technique or CV-atrial preparations with the optical mapping technique. Preparations were dissected from male Wistar rats of different ages (1, 3, 7, 14, 21 and 60 day of postnatal development). Results. Without electrical pacing in 50% of CV preparations of 1-7 days old rats demonstrated a spontaneous activity that appeared in a permanent manner. In 67% of spontaneously active preparations action potentials (AP) had a phase of slow diastolic depolarization resembling pacemaker-like AP. During aging, the AP shape turned to atrial-like, with rapid upstroke phase, and the ability of isolated CV preparations to perform automaticity gradually decreased. There was no spontaneous AP under basal conditions in 60 days old rats’ CV. In optical mapping experiments in CV-atrial preparations almost in all cases we observed an anterograde propagation of excitation and the focus of automaticity initiation was located in the right atrium region. However, in 30% of newborn rats on the 1 day of postnatal development we observed retrograde conduction with the excitation focus in CV myocardium and not in the right atrium region (Fig.1). Conclusion. In this study we demonstrated for the first time that the formation of a leading pacemaker continues during early postnatal life. We also showed that at the early steps of postnatal development CV myocardium can play a role of a normal pacemaker. Probably, the observed processes can be a reflection of changes of the level of transcription factors that determine the electrophysiological phenotype in CV myocardium.