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.
Highlights
The heart consists of atria and ventricles which at a cellular level are activated through excitation–contraction coupling in a highly coordinated fashion to provide sufficient pressure to maintain perfusion of the body
A principal component analysis (PCA) was carried out to assess if cardiomyocytes from AT, left ventricle (LV), right ventricle (RV), and interventricular septum (IVS) display clustering based on their respective origin (Figure 4D)
The large-scale dataset obtained in this study provides an accurate estimation of the variation that is present among ventricular cardiomyocytes
Summary
The heart consists of atria and ventricles which at a cellular level are activated through excitation–contraction coupling in a highly coordinated fashion to provide sufficient pressure to maintain perfusion of the body. The structural and contractile properties of each compartment are linked to the hemodynamic function it fulfills. The atria function predominantly as a reservoir for venous return and under normal circumstances does not have to overcome high pressures during contraction, which is reflected by highly elastic properties of the atrial myocardium (Blume et al, 2011). Functional differences between the chambers of the heart are apparent in the differential response to changes in hemodynamics, such as chronic pressure overload (Belin et al, 2011; Rain et al, 2014)
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