Modulation of the cardiomyocyte contraction inside a hydrostatic pressure bioreactor: textit{in vitro} verification of the Frank-Starling law

📝 Abstract

We have studied beating mouse cardiac syncytia $\textit{in vitro}$ in order to assess the inotropic, ergotropic, and chronotropic effects of both increasing and decreasing hydrostatic pressures. In particular, we have performed an image processing analysis to evaluate the kinematics and the dynamics of those pressure-loaded beating syncytia starting from the video registration of their contraction movement. By this analysis, we have verified the Frank-Starling law of the heart in $\textit{in vitro}$ beating cardiac syncytia and we have obtained their geometrical-functional classification.

💡 Analysis

We have studied beating mouse cardiac syncytia $\textit{in vitro}$ in order to assess the inotropic, ergotropic, and chronotropic effects of both increasing and decreasing hydrostatic pressures. In particular, we have performed an image processing analysis to evaluate the kinematics and the dynamics of those pressure-loaded beating syncytia starting from the video registration of their contraction movement. By this analysis, we have verified the Frank-Starling law of the heart in $\textit{in vitro}$ beating cardiac syncytia and we have obtained their geometrical-functional classification.

📄 Content

Research Article Modulation of the Cardiomyocyte Contraction inside a Hydrostatic Pressure Bioreactor: In Vitro Verification of the Frank-Starling Law Lorenzo Fassina,1,2 Giovanni Magenes,1,2 Roberto Gimmelli,3 and Fabio Naro4 1Dipartimento di Ingegneria Industriale e dell’Informazione, Universita di Pavia, Via Ferrata 1, 27100 Pavia, Italy 2Centro di Ingegneria Tissutale (CIT), Universita di Pavia, 27100 Pavia, Italy 3Dipartimento di Medicina Sperimentale, Universita “Sapienza”, 00161 Roma, Italy 4Dipartimento di Scienze Anatomiche, Istologiche, Medico-Legali e dell’Apparato Locomotore, Universita “Sapienza”, 00161 Roma, Italy Correspondence should be addressed to Lorenzo Fassina; lorenzo.fassina@unipv.it Received 24 July 2014; Revised 18 October 2014; Accepted 27 October 2014 Academic Editor: Kibret Mequanint Copyright © 2015 Lorenzo Fassina et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. We have studied beating mouse cardiac syncytia in vitro in order to assess the inotropic, ergotropic, and chronotropic effects of both increasing and decreasing hydrostatic pressures. In particular, we have performed an image processing analysis to evaluate the kinematics and the dynamics of those pressure-loaded beating syncytia starting from the video registration of their contraction movement. By this analysis, we have verified the Frank-Starling law of the heart in in vitro beating cardiac syncytia and we have obtained their geometrical-functional classification.

1. Introduction Understanding how cells react to mechanical forces is crucial. For instance, when osteoblasts sense a fluid shear stress, stretch-gated ion channels open and specific intracellular mechanisms lead to an enhanced production of bone matrix [1–3]. On the other hand, both tension and compression modulate the expression of transcription factors essential for the homeostasis of bone, cartilage, and tooth tissues [4]. Compression has a role during embryogenesis, when the blas- tocoel fluid presses the inner cell mass and, as a consequence, activates the key transcription factors OCT4, SOX2, and NANOG that determine pluripotency in the epiblast [5–7]. Tension and compression may also change the transcription more rapidly when they are transmitted directly into the nucleus via the cytoskeleton linked to nuclear envelope proteins [8]. The preceding examples of structure/force/function rela- tionships are well understandable in the frame of the “tenseg- rity” theory [9–13]: the functions of cells and tissues can be modulated not only by molecules, but also by biophysical stimuli. In particular, during the in vitro culture inside bioreactors, the biophysical forces may modify a specific cell status of force equilibrium, named “tensegrity,” inducing, via mechanotransduction, changes to the transcriptional profile. In general, the mechanical bioreactors elicit time varying forces acting perpendicularly or tangentially onto the cells and modulating the cell tensegrity via tensile, compressive, and shear deformations [14, 15]. In the present study, an instantaneous modulation of the cell function (without the involvement of transcriptional mechanisms) is well exemplified by the cardiomyocytes sub- jected to mechanical forces according to the Frank-Starling law of the heart [16]. In a previous work, to extend the possible use of beating cardiac syncytia cultured in vitro (e.g., in studies about human cardiac syncytium in physiological and pathologi- cal conditions, patient-tailored therapeutics, and syncytium models derived from induced pluripotent/embryonic stem cells with genetic mutations), we have developed a novel method based on image processing analysis to evaluate the kinematics and the dynamics of in vitro beating syncytia Hindawi Publishing Corporation BioMed Research International Volume 2015, Article ID 542105, 7 pages http://dx.doi.org/10.1155/2015/542105 2 BioMed Research International starting from the video registration of their contraction movement [17]: in particular, our method uses the dis- placement vector field and the velocity vector field of a beating patch to evaluate the syncytium not only from the chronotropic viewpoint, but also from the inotropic and ergotropic ones. In the present work, the preceding calculus method allowed the study of the mechanical modulation of the contraction properties in in vitro beating cardiac syncytia as they were loaded with different hydrostatic pressures inside a bioreactor. In particular, the computed kinematic and dynamic parameters aimed at revealing the inotropic, ergotropic, and chronotropic effects of the applied hydrostatic pressures: we anticipate that the data analysis permitted the verification of the Frank-Starling law in in vitro beating cardiac syncytia and their geometrical-functional classifica- tion.
2. Materi

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