Learn More
The duration of diastole can be defined in terms of mechanical events. Mechanical diastolic duration (MDD) is comprised by the phases of early rapid filling (E wave), diastasis, and late atrial filling (A wave). The effect of heart rate (HR) on diastolic duration is predictable from kinematic modeling and known cellular physiology. To determine the(More)
We investigated the cellular and molecular mechanisms of diastolic dysfunction in pure volume overload induced by aortocaval fistula (ACF) surgery in the mouse. Four weeks of volume overload resulted in significant biventricular hypertrophy; protein expression analysis in left ventricular (LV) tissue showed a marked decrease in titin's N2BA/N2B ratio with(More)
Titin-based passive stiffness is post-translationally regulated by several kinases that phosphorylate specific spring elements located within titin's elastic I-band region. Whether titin is phosphorylated by calcium/calmodulin dependent protein kinase II (CaMKII), an important regulator of cardiac function and disease, has not been addressed. The aim of(More)
Transmitral Doppler echocardiography is the preferred method of noninvasive diastolic function assessment. Correlations between catheterization-based measures of isovolumic relaxation (IVR) and transmitral, early rapid filling (Doppler E-wave)-derived parameters have been observed, but no model-based, causal explanation has been offered. IVR has also been(More)
Titin is a molecular spring that determines the passive stiffness of muscle cells. Changes in titin's stiffness occur in various myopathies, but whether these are a cause or an effect of the disease is unknown. We studied a novel mouse model in which titin's stiffness was slightly increased by deleting nine immunoglobulin (Ig)-like domains from titin's(More)
Viscosity is proposed to modulate diastolic function, but only limited understanding of the source(s) of viscosity exists. In vitro experiments have shown that the proline-glutamic acid-valine-lysine (PEVK) rich element of titin interacts with actin, causing a viscous force in the sarcomere. It is unknown whether this mechanism contributes to viscosity in(More)
Heart failure is associated with pump dysfunction and remodeling but it is not yet known if the condition affects different transmural regions of the heart in the same way. We tested the hypotheses that the left ventricles of non-failing human hearts exhibit transmural heterogeneity of cellular level contractile properties, and that heart failure produces(More)
Physiologists and cardiologists estimate peak transvalvular pressure gradients (DeltaP) by Doppler echocardiographic imaging of peak flow velocities using the simplified Bernoulli relationship: DeltaP (mm Hg) = 4V(2) (m/s). Because left ventricular filling is initiated by mechanical suction, V can be predicted by the motion of a simple harmonic oscillator(More)
Actin-myosin interactions provide the driving force underlying each heartbeat. The current view is that actin-bound regulatory proteins play a dominant role in the activation of calcium-dependent cardiac muscle contraction. In contrast, the relevance and nature of regulation by myosin regulatory proteins (for example, myosin light chain-2 [MLC2]) in cardiac(More)