Quantification of Beat-To-Beat Variability of Action Potential Durations in Langendorff-Perfused Mouse Hearts

Abstract

Background: Beat-to-beat variability in action potential duration (APD) is an intrinsic property of cardiac tissue and is altered in pro-arrhythmic states. However, it has never been examined in mice.Methods: Left atrial or ventricular monophasic action potentials (MAPs) were recorded from Langendorff-perfused mouse hearts during regular 8 Hz pacing. Time-domain, frequency-domain and non-linear analyses were used to quantify APD variability.Results: Mean atrial APD (90% repolarization) was 23.5 ± 6.3 ms and standard deviation (SD) was 0.9 ± 0.5 ms (n = 6 hearts). Coefficient of variation (CoV) was 4.0 ± 1.9% and root mean square (RMS) of successive differences in APDs was 0.3 ± 0.2 ms. The peaks for low- and high-frequency were 0.7 ± 0.5 and 2.7 ± 0.9 Hz, respectively, with percentage powers of 39.0 ± 20.5 and 59.3 ± 22.9%. Poincaré plots of APDn+1 against APDn revealed ellipsoid shapes. The ratio of the SD along the line-of-identity (SD2) to the SD perpendicular to the line-of-identity (SD1) was 8.28 ± 4.78. Approximate and sample entropy were 0.57 ± 0.12 and 0.57 ± 0.15, respectively. Detrended fluctuation analysis revealed short- and long-term fluctuation slopes of 1.80 ± 0.15 and 0.85 ± 0.29, respectively. When compared to atrial APDs, ventricular APDs were longer (ANOVA, P < 0.05), showed lower mean SD and CoV but similar RMS of successive differences in APDs and showed lower SD2 (P < 0.05). No difference in the remaining parameters was observed.Conclusion: Beat-to-beat variability in APD is observed in mouse hearts during regular pacing. Atrial MAPs showed greater degree of variability than ventricular MAPs. Non-linear techniques offer further insights on short-term and long-term variability and signal complexity.

Arrhythmogenic Mechanisms in Hypokalaemia: Insights From Pre-clinical Models

“…An equation encapsulating this concept was coined in 1979 as heart weight (HW (g) = 6.0 × BM 0.98 ) and P-R interval (PR (ms) = 53 × BM 0.24 ) where BM is body mass in kg ( 83 ). Such differences are reinforced in electrophysiology, where small rodents are found with significantly shorter APD than humans due to lack of a prominent plateau phase found in cardiomyocytes ( 84 – 86 ). Therefore, the rabbit myocardium presents a more representative model of the human heart.…”

Measures of repolarization variability predict ventricular arrhythmogenesis in heptanol-treated Langendorff-perfused mouse hearts

“…For example, it can predict pro-arrhythmic outcomes in patients with non-ischemic heart failure ( Hinterseer et al., 2010 ). Recently, we reported in the mouse species for the first time the use of time-, frequency-, time-frequency and non-linear analyses for quantifying APD variability in the atria and ventricles ( Tse et al., 2018 ). Here, we extend these findings by reporting that higher degrees of repolarization variability and irregularity can predict ventricular arrhythmogenesis.…”

“…APD variability can be affected by different physiological states, such as the extent of intercellular coupling ( Zaniboni et al., 2000 ), redox changes ( Kistamas et al., 2015a ), abnormal calcium dynamics ( Kistamas et al., 2015b ) or time taken for full repolarization ( Abi-Gerges et al., 2010 ). Recently, our team reported the use of both time-domain and non-linear analyses to quantify APD variability for the first time in mouse hearts ( Tse et al., 2018 ). Theoretically, the loss of intercellular coupling can increase this variability ( Magyar et al., 2015 ), which could precipitate arrhythmogenesis.…”

Integration of computer-simulated practical exercises into undergraduate medical pharmacology education at Mulungushi University, Zambia

“…The effects of drugs on the cardiovascular system could be demonstrated in several ways during laboratory classes. Isolated whole organ preparations such as the Langendorff perfusion system have been used to study the effects of drugs on the heart [ 12 ]. Organ baths could also be used to study the contractile or relaxant effects of drugs on the vasculature (e.g., using aortic rings) [ 13 ].…”