Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Apr 4:9:147.
doi: 10.3389/fphys.2018.00147. eCollection 2018.

Beat-to-Beat Variability of Ventricular Action Potential Duration Oscillates at Low Frequency During Sympathetic Provocation in Humans

Bradley Porter  1 , Stefan van Duijvenboden  2 , Martin J Bishop  1 , Michele Orini  2 , Simon Claridge  1 , Justin Gould  1 , Benjamin J Sieniewicz  1 , Baldeep Sidhu  1 , Reza Razavi  1 , Christopher A Rinaldi  3 , Jaswinder S Gill  3 , Peter Taggart  2
Affiliations

Beat-to-Beat Variability of Ventricular Action Potential Duration Oscillates at Low Frequency During Sympathetic Provocation in Humans

Bradley Porter et al. Front Physiol. .

Abstract

Background: The temporal pattern of ventricular repolarization is of critical importance in arrhythmogenesis. Enhanced beat-to-beat variability (BBV) of ventricular action potential duration (APD) is pro-arrhythmic and is increased during sympathetic provocation. Since sympathetic nerve activity characteristically exhibits burst patterning in the low frequency range, we hypothesized that physiologically enhanced sympathetic activity may not only increase BBV of left ventricular APD but also impose a low frequency oscillation which further increases repolarization instability in humans. Methods and Results: Heart failure patients with cardiac resynchronization therapy defibrillator devices (n = 11) had activation recovery intervals (ARI, surrogate for APD) recorded from left ventricular epicardial electrodes alongside simultaneous non-invasive blood pressure and respiratory recordings. Fixed cycle length was achieved by right ventricular pacing. Recordings took place during resting conditions and following an autonomic stimulus (Valsalva). The variability of ARI and the normalized variability of ARI showed significant increases post Valsalva when compared to control (p = 0.019 and p = 0.032, respectively). The oscillatory behavior was quantified by spectral analysis. Significant increases in low frequency (LF) power (p = 0.002) and normalized LF power (p = 0.019) of ARI were seen following Valsalva. The Valsalva did not induce changes in conduction variability nor the LF oscillatory behavior of conduction. However, increases in the LF power of ARI were accompanied by increases in the LF power of systolic blood pressure (SBP) and the rate of systolic pressure increase (dP/dtmax). Positive correlations were found between LF-SBP and LF-dP/dtmax (rs = 0.933, p < 0.001), LF-ARI and LF-SBP (rs = 0.681, p = 0.001) and between LF-ARI and LF-dP/dtmax (rs = 0.623, p = 0.004). There was a strong positive correlation between the variability of ARI and LF power of ARI (rs = 0.679, p < 0.001). Conclusions: In heart failure patients, physiological sympathetic provocation induced low frequency oscillation (~0.1 Hz) of left ventricular APD with a strong positive correlation between the LF power of APD and the BBV of APD. These findings may be of importance in mechanisms underlying stability/instability of repolarization and arrhythmogenesis in humans.

Keywords: action potential duration variability; activation recovery interval; arrhythmia; oscillations; sympathetic nervous system.

PubMed Disclaimer

Figures

Figure 1
Figure 1
(A) Cardiac resynchronization therapy defibrillator (CRT-D) device programmed to pace from the right ventricular (RV) electrode and record a local unipolar electrogram (UEG) from the left ventricular (LV) electrode. (B) Relationship between the unipolar electrogram and the intracellular ventricular transmembrane potential showing correspondence between activation recovery interval (ARI) and action potential duration (APD). (C) Example UEG recorded from the left ventricular lead and the computed ARI values for the same electrogram trace.
Figure 2
Figure 2
Power spectral analysis of low-frequency (LF, 0.04–0.15 Hz) and high-frequency (HF, 0.15–0.4 Hz) variability. This example shows a clear increase of LF variability of ARI in one patient following the Valsalva. PSD, Power spectrum density; PLF, low frequency power; PHF, high frequency power.
Figure 3
Figure 3
Individual beat-to-beat variability measures of (A) activation recovery intervals (ARIs), (B) systolic blood pressure (SBP) and (C) the maximum rate of systolic pressure increase (dP/dtmax) at rest and following the Valsalva. SD, Standard deviation, nSD, Normalized SD.
Figure 4
Figure 4
Effect of Valsalva on low frequency (LF) power and normalized LF (nLF) power of (A) activation recovery intervals (ARIs), (B) systolic blood pressure (SBP), and (C) the maximum rate of systolic pressure increase (dP/dtmax) at rest and following the Valsalva.
Figure 5
Figure 5
Scatterplot demonstrating the significant correlation between low frequency (LF) power of systolic blood pressure (SBP) and the LF power of the maximum rate of systolic pressure increase (dP/dtmax).
Figure 6
Figure 6
Scatterplot demonstrating the significant correlation between the low frequency (LF) power of activation recovery intervals (ARIs) and the beat-to-beat variability of ARI (SDARI).
See this image and copyright information in PMC

References

    1. Abi-Gerges N., Valentin J.-P., Pollard C. E. (2010). Dog left ventricular midmyocardial myocytes for assessment of drug-induced delayed repolarization: short-term variability and proarrhythmic potential. Br. J. Pharmacol. 159, 77–92. 10.1111/j.1476-5381.2009.00338.x - DOI - PMC - PubMed
    1. Akaike H. (1974). A new look at the statistical model identification. IEEE Trans. Autom. Control 19, 716–723. 10.1109/TAC.1974.1100705 - DOI
    1. Atiga W. L., Calkins H., Lawrence J. H., Tomaselli G. F., Smith J. M., Berger R. D. (1998). Beat-to-beat repolarization lability identifies patients at risk for sudden cardiac death. J. Cardiovasc. Electrophysiol. 9, 899–908. 10.1111/j.1540-8167.1998.tb00130.x - DOI - PubMed
    1. Baumert M., Porta A., Vos M. A., Malik M., Couderc J.-P., Laguna P., et al. (2016). QT interval variability in body surface ECG: measurement, physiological basis, and clinical value: position statement and consensus guidance endorsed by the European heart rhythm association jointly with the ESC Working Group on Cardiac Cellular Electrophysiology. Europace 18, 925–944. 10.1093/europace/euv405 - DOI - PMC - PubMed
    1. Booth R. W., Ryan J. M., Mellett H. C., Swiss E., Neth E. (1962). Hemodynamic changes associated with the Valsalva maneuver in normal men and women. J. Lab. Clin. Med. 59, 275–285.

LinkOut - more resources