Beating Rate Variability of Isolated Mammal Sinoatrial Node Tissue: Insight Into Its Contribution to Heart Rate Variability

Abstract

BackgroundBecause of the complexity of the interaction between the internal pacemaker mechanisms, cell interconnected signals, and interaction with other body systems, study of the role of individual systems must be performed under in vivo and in situ conditions. The in situ approach is valuable when exploring the mechanisms that govern the beating rate and rhythm of the sinoatrial node (SAN), the heart’s primary pacemaker. SAN beating rate changes on a beat-to-beat basis. However, to date, there are no standard methods and tools for beating rate variability (BRV) analysis from electrograms (EGMs) collected from different mammals, and there is no centralized public database with such recordings.MethodsWe used EGM recordings obtained from control SAN tissues of rabbits (n = 9) and mice (n = 30) and from mouse SAN tissues (n = 6) that were exposed to drug intervention. The data were harnessed to develop a beat detector to derive the beat-to-beat interval time series from EGM recordings. We adapted BRV measures from heart rate variability and reported their range for rabbit and mouse.ResultsThe beat detector algorithm performed with 99% accuracy, sensitivity, and positive predictive value on the test (mouse) and validation (rabbit and mouse) sets. Differences in the frequency band cutoff were found between BRV of SAN tissue vs. heart rate variability (HRV) of in vivo recordings. A significant reduction in power spectrum density existed in the high frequency band, and a relative increase was seen in the low and very low frequency bands. In isolated SAN, the larger animal had a slower beating rate but with lower BRV, which contrasted the phenomena reported for in vivo analysis. Thus, the non-linear inverse relationship between the average HR and HRV is not maintained under in situ conditions. The beat detector, BRV measures, and databases were contributed to the open-source PhysioZoo software (available at: https://physiozoo.com/).ConclusionOur approach will enable standardization and reproducibility of BRV analysis in mammals. Different trends were found between beating rate and BRV or HRV in isolated SAN tissue vs. recordings collected under in vivo conditions, respectively, implying a complex interaction between the SAN and the autonomic nervous system in determining HRV in vivo.

Opening the Schrödinger Box: Short- and Long-Range Mammalian Heart Rate Variability

“…Thus, for mice, extrinsic mechanisms shift the power from LF to VLF under ABK conditions. In isolated SAN from rabbit ( Shemla et al, 2021 ) (as shown in Figure 2F ) or isolated heart ( Frey et al, 1996 ), the majority of PSD was in the VLF regime. Thus, for rabbits, the extrinsic contribution is minor compared to intrinsic pacemaker mechanisms.…”

“…Finally, to estimate the relative contribution of the extrinsic vs. intrinsic pacemaker mechanisms to the heartbeat interval of each mammal, we compared the ABK data to published results on isolated tissue ( Shemla et al, 2021 ) or isolated heart ( Frey et al, 1996 ). As shown in Figure 2E , in the isolated sinoatrial node (SAN) from mice (including only the intrinsic pacemaker mechanisms), the majority of PSD was in the LF regime, and the remaining power was in the VLF ( Shemla et al, 2021 ). Thus, for mice, extrinsic mechanisms shift the power from LF to VLF under ABK conditions.…”

Morphometric parameters of the heart of domestic sheep Ovis aries L., 1758

“…From the point of view of mechanics, according to studies (Shemla et al, 2021;Weiser-Bitoun et al, 2021), the heart can be considered as a mechanism consisting of two discharge pumps formed into a closed system of tubes through which fluid (blood) circulates. In this case, the pumps create a directed blood flow in the appropriate direction.…”

Anatomical and morphological features of the heart of a domestic dog (Canis Lupus Familiaris L., 1758)

“…З погляду механіки, згідно досліджень (Shemla et al, 2021;Weiser-Bitoun et al, 2021), серце можна розглядати як механізм, що складається з двох нагнітальних насосів, сформованих у замкнуту систему трубок, якими циркулює рідина (кров). У цьому випадку насоси служать для створення спрямованого потоку крові у відповідному напрямку.…”