Abstract Title

Differences in Actomyosin Function in the Left and Right Ventricles of Human Hearts

RAD Assignment Number

423

Presenter Name

Sebastian Requena

Abstract

Purpose: In both ventricles of the heart, actin is expressed from the same genes. There are no differences in twitch duration, work performance, and power among the right (RV) and left (LV) ventricles in animals. So there is no expectation that the properties of actin or myosin isolated from either ventricle would be different. Nevertheless, the situation is more complex in human hearts. The LV must pump more powerfully because it has to overcome a larger resistance presented by the systemic system than the RV, which has to overcome a lower resistance offered by the pulmonary system. The question arises whether stronger pumping action of the LV is partially caused by the LV actomyosin developing more force than the RV actomyosin. The goal of this work is too identify if there are any differences in the kinetics rates of the actomyosin mechanochemical cycle in the LV versus the RV.

Methods: Such a question is impossible to answer by making macroscopic measurements such as tension or ATPase activity, because the number of molecules involved in these processes is too large, (of the order of 1011) Measurements must be taken from a few molecules. We measured variations in the polarization of fluorescence of a few actomyosin molecules during the contraction cycle using time-resolved single molecule fluorescent microscopy. We obtained molecular kinetic information by calculating its autocorrelation function using R (version 3.3.1). The autocorrelation curve was fitted with a bi-exponential decay model to extract the rate constants using XPFIT (version 1.2.1) The goodness of fit was assessed by chi-squared.

Results: The results suggest that actomyosin function is identical in both ventricles. There are no statistically significant differences in the kinetic rates that we obtained. Additionally, the spatial distribution of actomyosin is also the same.

Conclusions: Our results suggest that the differences in the LV and RV may not be due to differences at the molecular level between actomyosin from the LV or RV in human hearts. However, our study only involved the use of failing human hearts with a wide variety of clinical parameters. These differences in the type of heart failures and patients may mean that we will not be able to extract statistically different results between kinetic rates. We have begun working on non-failing human hearts and will see if differences are present in that case.

Research Area

Cardiovascular

Presentation Type

Poster

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Differences in Actomyosin Function in the Left and Right Ventricles of Human Hearts

Purpose: In both ventricles of the heart, actin is expressed from the same genes. There are no differences in twitch duration, work performance, and power among the right (RV) and left (LV) ventricles in animals. So there is no expectation that the properties of actin or myosin isolated from either ventricle would be different. Nevertheless, the situation is more complex in human hearts. The LV must pump more powerfully because it has to overcome a larger resistance presented by the systemic system than the RV, which has to overcome a lower resistance offered by the pulmonary system. The question arises whether stronger pumping action of the LV is partially caused by the LV actomyosin developing more force than the RV actomyosin. The goal of this work is too identify if there are any differences in the kinetics rates of the actomyosin mechanochemical cycle in the LV versus the RV.

Methods: Such a question is impossible to answer by making macroscopic measurements such as tension or ATPase activity, because the number of molecules involved in these processes is too large, (of the order of 1011) Measurements must be taken from a few molecules. We measured variations in the polarization of fluorescence of a few actomyosin molecules during the contraction cycle using time-resolved single molecule fluorescent microscopy. We obtained molecular kinetic information by calculating its autocorrelation function using R (version 3.3.1). The autocorrelation curve was fitted with a bi-exponential decay model to extract the rate constants using XPFIT (version 1.2.1) The goodness of fit was assessed by chi-squared.

Results: The results suggest that actomyosin function is identical in both ventricles. There are no statistically significant differences in the kinetic rates that we obtained. Additionally, the spatial distribution of actomyosin is also the same.

Conclusions: Our results suggest that the differences in the LV and RV may not be due to differences at the molecular level between actomyosin from the LV or RV in human hearts. However, our study only involved the use of failing human hearts with a wide variety of clinical parameters. These differences in the type of heart failures and patients may mean that we will not be able to extract statistically different results between kinetic rates. We have begun working on non-failing human hearts and will see if differences are present in that case.