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Contractility Measurements on Isolated Papillary Muscles for the Investigation of Cardiac Inotropy in Mice
Published on: September 17, 2015
The beat-to-beat decay of cardiac contractility from highly potentiated levels is bi-exponential
Mark I M Noble1, Per Arlock, Bjorn Wohlfart
1Department of Cardiology, University of Aberdeen, UK. mimnoble@freenetname.co.uk
Insights
Cardiac contractility decay deviates from simple models at high levels. A faster initial decay followed by a slower one, a bi-exponential pattern, was observed in ferret papillary muscle.
Area of Science:
- Cardiology
- Physiology
- Biophysics
Background:
- Cardiac contractility decay is typically modeled using mono-exponential functions.
- This model assumes a fixed fraction of activator calcium ions are recirculated between heartbeats.
- Deviations may occur at very high contractility levels.
Purpose of the Study:
- To investigate the beat-to-beat decay of cardiac contractility following potentiation.
- To determine if contractility decay deviates from mono-exponential models at high levels.
Main Methods:
- Studied beat-by-beat decay of cardiac contractility in isolated ferret papillary muscle.
- Utilized potentiation via prolonged depolarizations to achieve high contractility.
- Employed single sucrose-gap voltage clamp techniques.
- Analyzed decay curves using mono-exponential fitting and analysis of covariance.
Main Results:
- A bi-exponential decay pattern was observed in 9 out of 11 muscles studied.
- The initial decay phase was significantly faster than the subsequent slower phase.
- The slower decay phase, within the physiological range, matched decay after post-extrasystolic potentiation.
Conclusions:
- Cardiac contractility decay at high levels is better described by a bi-exponential model, not mono-exponential.
- This suggests a more complex mechanism for calcium ion handling during potentiation.
- The findings have implications for understanding cardiac function under stress.
Abstract:
In order to determine the mode of beat-to-beat decay of contractility from very high levels, we studied the beat-by-beat decay of cardiac contractility following potentiation. Such decay curves are normally analysed using a mono-exponential decay function, which assumes that a fixed fraction of activator calcium ions is recirculated from one beat to the next. We postulated that there might be deviations from such a mono-exponential expression at high levels of contractility. In single sucrose-gap voltage clamp experiments of isolated ferret papillary muscle, we obtained very high contractility by potentiation due to prolonged depolarisations. We found a bi-exponential decay in 9 of 11 muscles studied, in which the initial decay is much faster than the subsequent slower decay, as judged by residual variance of least-squares exponential fitting and by analysis of covariance using a linear equation (force of beat versus force of previous beat), p = 0.0089. In the slower decay period (physiological range), the decay was identical to that following post-extrasystolic potentiation in the same muscles studied with conventional stimulation.
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