Contractile Differences In Left And Right Ventricles Of Healthy Human Hearts

Left ventricle (LV) and right ventricle (RV) differ in embryology, structure and function. Left ventricle originates from the primary heart field while right ventricle originates from the secondary heart field. The two heart fields express different sets of transcription factors and signaling molecules. At the molecular level, the gene expression in response to the pressure loading and failure is different in both ventricles. They also exhibit differences in response to adrenergic stimulation. Adrenergic agonist increase LV contractility but RV contractility may be reduced. Although numerous studies have been performed at macroscopic (whole organ) level previously, none (to my knowledge) address the differences at a mesoscopic level, where only a few molecules are investigated. This becomes important, as in macroscopic studies there may be differences due to basic fiber structures, differences in orientation of fibers as well as molecular crowding. These differences were investigated at the level of few molecules by sparsely labeling the myosin lever arm with SeTau 647 Maleimide. The kinetics and steady-state distribution of cross-bridges were examined in ex-vivo myofibrils isolated from the ventricles of human non-failing and failing hearts and differences were compared in LV and RV. We show that the kinetics and the steady-state distribution of orientations of myosin were different in contracting LV and RV of the non-failing human heart. In contrast, kinetics and the steady-state distribution of myosin in the failing hearts were the same. These results suggest that there is a difference in the way actin interacts with myosin cross-bridges in ventricles of non-failing hearts. We compare the clinical parameters of the failing heart with the kinetics and the distribution of the non-failing heart, and suggest molecular effectors of the function of myosin.