A significant proportion of patients placed on long-term mechanical circulatory support for end-stage heart failure can be weaned from mechanical assistance after functional recovery of their native heart ("bridge to recovery"). The pathophysiological mechanisms implicated in reverse remodeling that cause a sustained functional myocardial recovery have recently become the subject of intensive research, expected to provide information with a view to accurately identify reliable prognostic indicators of recovery. In addition, this kind of information will enable changes in the strategy of myocardial recovery by modifying the duration and scale of the unloading regimen or by combining it with other treatments that promote reverse remodeling.
"These observations form the basis of our proposed constitutive model for reversible strain-driven growth. The original concept of reverse remodeling was spawned by the effects of left ventricular assist devices in normalizing end-diastolic pressure–volume relationship in patients with end-stage cardiomyopathy (Levin et al. 1995) that have been frequently observed in clinical practice (Burkhoff et al. 2006; Drakos et al. 2007; Ambardekar and Buttrick 2011). In particular, prolonged unloading of the left ventricular pressure (and volume) after left ventricular assist device implantation (Figure 1 in Burkhoff et al. (2006)) led to two key global features, namely, a decrease in left ventricular volume and a concurrent leftward shift in the end-diastolic pressure– volume relationship (Figure 2 in Levin et al. (1995)). "
[Show abstract][Hide abstract] ABSTRACT: Ventricular growth is widely considered to be an important feature in the adverse progression of heart diseases, whereas reverse ventricular growth (or reverse remodeling) is often considered to be a favorable response to clinical intervention. In recent years, a number of theoretical models have been proposed to model the process of ventricular growth while little has been done to model its reverse. Based on the framework of volumetric strain-driven finite growth with a homeostatic equilibrium range for the elastic myofiber stretch, we propose here a reversible growth model capable of describing both ventricular growth and its reversal. We used this model to construct a semi-analytical solution based on an idealized cylindrical tube model, as well as numerical solutions based on a truncated ellipsoidal model and a human left ventricular model that was reconstructed from magnetic resonance images. We show that our model is able to predict key features in the end-diastolic pressure-volume relationship that were observed experimentally and clinically during ventricular growth and reverse growth. We also show that the residual stress fields generated as a result of differential growth in the cylindrical tube model are similar to those in other nonidentical models utilizing the same geometry.
Biomechanics and Modeling in Mechanobiology 06/2014; 14(2). DOI:10.1007/s10237-014-0598-0 · 3.15 Impact Factor
"More prolonged in duration evaluation tests (than the ones used in most of the studies until now), using operation of the pump at the lowest possible rates in terms of safety, need to be tested in future studies. • Histological, cellular and molecular indices of genuine recovery (as opposed to simple markers of unloading) are the subject of intense research and are expected to greatly contribute to the accurate diagnosis of significant ventricular recovery during mechanical support (Drakos et al., 2007). LVADs designed specifically for recovery (easily implantable and explantable, atraumatic to the myocardium, operating in coordination with the native heart) are currently under development and may find a place in clinical practice in the future (Nanas et al., 1996). "
[Show abstract][Hide abstract] ABSTRACT: Recreating ancestral proteins in the laboratory increasingly is being used to study the evolutionary history of protein function. More efficient gene synthesis techniques and the decreasing costs of commercial oligosynthesis are making this approach both simpler and less expensive to perform. Developments in ancestral reconstruction methods, particularly more realistic likelihood models of molecular evolution, allow for the accurate reconstruction of more ancient proteins than previously possible. This chapter reviews phylogenetic methods of ancestral inference, strategies for investigating alternative reconstructions, gene synthesis, and design, and an application of these methods to the reconstruction of an ancestor in the green fluorescent protein family.
Methods in Enzymology 02/2005; 395:652-70. DOI:10.1016/S0076-6879(05)95034-9 · 2.09 Impact Factor
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