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Published on: September 17, 2015
Large-Scale Contractility Measurements Reveal Large Atrioventricular and Subtle Interventricular Differences in
Edgar E Nollet1, Emmy M Manders2, Max Goebel1
1Department of Physiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands.
Insights
Heart chamber cells have different contractile properties. Atrial cells are less contractile than ventricular cells, but differences between right and left ventricles are small, only partly explaining organ-level function.
Area of Science:
- Cardiovascular Physiology
- Cellular Mechanics
- Cardiac Electrophysiology
Background:
- Heart chambers (atria, ventricles) have distinct hemodynamic roles influencing their structure and function.
- The atria are elastic for venous filling, while ventricles generate high pressures for circulation.
- Differences in cardiomyocyte contractility may explain chamber-specific functions, but this is not fully understood.
Purpose of the Study:
- To investigate contractile property differences among cardiomyocytes from rat atria, right ventricle (RV), left ventricle (LV), and interventricular septum (IVS).
- To determine if cardiomyocyte-level differences explain the functional distinctions between heart chambers.
Main Methods:
- Isolation of cardiomyocytes from rat atria, RV, LV, and IVS.
- High-throughput measurement of contractile function in 2,043 individual cardiomyocytes after overnight culture.
- Analysis of contraction amplitude, fractional shortening, and contraction/relaxation kinetics.
Main Results:
- Atrial cardiomyocytes exhibited twofold lower contraction amplitude and significantly slower kinetics compared to ventricular cells.
- RV cardiomyocytes showed only minor differences in fractional shortening and relaxation kinetics versus LV and IVS cells.
- Strong correlations were observed between contraction velocity, fractional shortening, and relaxation velocity.
Conclusions:
- Cardiomyocyte contractile differences align with atrioventricular functional distinctions.
- These cellular-level differences only partially account for the observed interventricular functional disparities at the organ level.
- Contractile parameters are highly interdependent, suggesting coordinated cellular behavior.
Abstract:
The chambers of the heart fulfill different hemodynamic functions, which are reflected in their structural and contractile properties. While the atria are highly elastic to allow filling from the venous system, the ventricles need to be able to produce sufficiently high pressures to eject blood into the circulation. The right ventricle (RV) pumps into the low pressure pulmonary circulation, while the left ventricle (LV) needs to overcome the high pressure of the systemic circulation. It is incompletely understood whether these differences can be explained by the contractile differences at the level of the individual cardiomyocytes of the chambers. We addressed this by isolating cardiomyocytes from atria, RV, LV, and interventricular septum (IVS) of five healthy wild-type rats. Using a high-throughput contractility set-up, we measured contractile function of 2,043 cells after overnight culture. Compared to ventricular cardiomyocytes, atrial cells showed a twofold lower contraction amplitude and 1.4- to 1.7-fold slower kinetics of contraction and relaxation. The interventricular differences in contractile function were much smaller; RV cells displayed 12-13% less fractional shortening and 5-9% slower contraction and 3-15% slower relaxation kinetics relative to their LV and IVS counterparts. Aided by a large dataset, we established relationships between contractile parameters and found contraction velocity, fractional shortening and relaxation velocity to be highly correlated. In conclusion, our findings are in line with contractile differences observed at the atrioventricular level, but can only partly explain the interventricular differences that exist at the organ level.

