Electrophysiological Effects of Extracellular Vesicles Secreted by Cardiosphere-Derived Cells: Unraveling the Antiarrhythmic Properties of Cell Therapies

Although cell-based therapies show potential antiarrhythmic effects that could be mediated by their paracrine action, the mechanisms and the extent of these effects were not deeply explored. We investigated the antiarrhythmic mechanisms of extracellular vesicles secreted by cardiosphere-derived cell extracellular vesicles (CDC-EVs) on the electrophysiological properties and gene expression profile of HL1 cardiomyocytes. HL-1 cultures were primed with CDC-EVs or serum-free medium alone for 48 h, followed by optical mapping and gene expression analysis. In optical mapping recordings, CDC-EVs reduced the activation complexity of the cardiomyocytes by 40%, increased rotor meandering, and reduced rotor curvature, as well as induced an 80% increase in conduction velocity. HL-1 cells primed with CDC-EVs presented higher expression of SCN5A, CACNA1C, and GJA1, coding for proteins involved in INa, ICaL, and Cx43, respectively. Our results suggest that CDC-EVs reduce activation complexity by increasing conduction velocity and modifying rotor dynamics, which could be driven by an increase in expression of SCN5A and CACNA1C genes, respectively. Our results provide new insights into the antiarrhythmic mechanisms of cell therapies, which should be further validated using other models.

Rotor Design and Optimization in Internal Lobe Pumps

The topic of this paper is the design of internal lobe pumps and their optimization which is based on specific performance indexes. Internal lobe pumps can be classified as different types depending on the shape of the lobe of the outer rotor. First, the design of internal lobe pumps with elliptical, sinusoidal, and polycircular lobe profiles is considered. The latter is a new type of lobe profile with special shape whose curvature follows a definite function. Then we introduce the performance indexes used for the comparison. Some of these indexes, such as the flow rate irregularity, are commonly used for performance comparison, while others, such as the specific slipping and the rotor curvature, are particularly suitable in this case. The comparisons are made with the circular type that had been analyzed by the authors in previous papers (see eg, Mimmi, Pannacchi, and Savi (1996), Internal Lobe Pump Design, Mechanics in design - Proc CSME Forum ’96, SA Meguid (ed), Toronto, Ontario, Canada). It is not easy to univocally state the superiority of one type with respect to the others, however, it is possible to notice that elliptical and polycircular types are comparable to the circular ones in terms of flow rate irregularity, but have improved performance in terms of specific slipping and rotor curvature.

On Rotor calculus, II

SummaryIn the development of the rotor calculus presented in a previous paper space-time was taken to be flat. This work is now extended to the case of curved space-times, which, in the first instance, is taken to be Riemannian. (The calculus bears at times a strong formal resemblance to the spinor analysis of Infeld and van der Waerden, but it is in fact developed quite independently of this.) Owing to the fact that all general relations had earlier already been written in a generally covariant form they may be taken over unchanged into the present context. In particular,now serves as a defining relation for the connecting quantities τAkl. A linear rotor connection is introduced, and the covariant derivative of a rotor defined. The covariant constancy of the τAkl establishes the relation between the linear connections in w-space and in r-space. A rotor curvature tensor is considered alongside a number of other curvature objects. Next, conformal transformations are dealt with, of which duality rotations may be considered as a special case. This leads naturally to a gauge-covariant generalization of the whole calculus. A so-called rotor-derivative is defined, and some general relations involving such derivatives investigated. The relation of the rotor curvature tensor to the spin-curvature tensor is touched upon, after which the introduction of “geodesic frames” is considered. After this general theory some points concerning the Maxwell field are dealt with, which is followed by some work concerning basic quadratic and cubic invariants. Finally, a certain basic symmetric rotor is re-considered in the context of the classification of Weyl tensors, and the idea of a canonical representation suggested.