The Effects of Mechanical Preload on Transmural Differences in Mechano-Calcium-Electric Feedback in Single Cardiomyocytes: Experiments and Mathematical Models

Transmural differences in ventricular myocardium are maintained by electromechanical coupling and mechano-calcium/mechano-electric feedback. In the present study, we experimentally investigated the influence of preload on the force characteristics of subendocardial (Endo) and subepicardial (Epi) single ventricular cardiomyocytes stretched by up to 20% from slack sarcomere length (SL) and analyzed the results with the help of mathematical modeling. Mathematical models of Endo and Epi cells, which accounted for regional heterogeneity in ionic currents, Ca2+ handling, and myofilament contractile mechanisms, showed that a greater slope of the active tension–length relationship observed experimentally in Endo cardiomyocytes could be explained by greater length-dependent Ca2+ activation in Endo cells compared with Epi ones. The models also predicted that greater length dependence of Ca2+ activation in Endo cells compared to Epi ones underlies, via mechano-calcium-electric feedback, the reduction in the transmural gradient in action potential duration (APD) at a higher preload. However, the models were unable to reproduce the experimental data on a decrease of the transmural gradient in the time to peak contraction between Endo and Epi cells at longer end-diastolic SL. We hypothesize that preload-dependent changes in viscosity should be involved alongside the Frank–Starling effects to regulate the transmural gradient in length-dependent changes in the time course of contraction of Endo and Epi cardiomyocytes. Our experimental data and their analysis based on mathematical modeling give reason to believe that mechano-calcium-electric feedback plays a critical role in the modulation of electrophysiological and contractile properties of myocytes across the ventricular wall. © Copyright © 2020 Khokhlova, Konovalov, Iribe, Solovyova and Katsnelson.AAAA-A18-118020590031-8Russian Foundation for Basic Research, RFBR: 18-01-00059Russian Science Foundation, RSF: 18-74-10059Funding. Wet experiments were supported by the Russian Science Foundation (#18-74-10059). The development of mouse ventricular cardiomyocyte model was supported by the Russian Foundation for Basic Research (#18-01-00059), IIF UrB RAS theme (AAAA-A18-118020590031-8), and by RF Government Act #211 of March 16, 2013 (agreement 02.A03.21.0006)

Transmural cellular heterogeneity in myocardial electromechanics

Myocardial heterogeneity is an attribute of the normal heart. We have developed integrative models of cardiomyocytes from the subendocardial (ENDO) and subepicardial (EPI) ventricular regions that take into account experimental data on specific regional features of intracellular electromechanical coupling in the guinea pig heart. The models adequately simulate experimental data on the differences in the action potential and contraction between the ENDO and EPI cells. The modeling results predict that heterogeneity in the parameters of calcium handling and myofilament mechanics in isolated ENDO and EPI cardiomyocytes are essential to produce the differences in Ca2+ transients and contraction profiles via cooperative mechanisms of mechano-calcium-electric feedback and may further slightly modulate transmural differences in the electrical properties between the cells. Simulation results predict that ENDO cells have greater sensitivity to changes in the mechanical load than EPI cells. These data are important for understanding the behavior of cardiomyocytes in the intact heart. © 2017, The Physiological Society of Japan and Springer Japan.Japan Society for the Promotion of Science, JSPS: 16K1287

Shakespeare: el texto bárbaro - el juego de espejos - el sueño asesinado - los caballos carnívoros : Apuntes sobre el texto espectacular de <i>Macbeth</i>

La noción de “puesta en escena” sustenta la hipótesis de que el teatro es un lugar de representación autónomo; un sistema lingüístico cuya operación significante reside más en la arbitrariedad que en la analogía; producción de signos ya no ligados a la producción mimética de los fenómenos de la realidad o con los procedimientos significantes de un texto literario, sino destinados a construir una realidad discursiva nueva y, sobre todo, a la creación de otra realidad con respecto a la objetualidad de la vida cotidiana. Esta ponencia se propone explorar recorridos posibles de la textualidad de Macbeth como hipótesis para una dramaturgia como mundo propio, como nuevo objeto de conocimiento.Facultad de Humanidades y Ciencias de la Educació

Transmural heterogeneity in the mechanical and electrical properties of cardiomyocytes. Experimental study and modeling

Supported by the Russia Foundation for Basic Research (14-01-00885, 14-01-31134), by Presidium of the Ural Branch of the Russian Academy of Sciences (12-M-14-2009, 12-П-4-1067) by Ural Federal University (Act 211 Government of the Russian Federation #02.A03.21.0006) and by JREX Fellowship for young researchers

Methods for investigating the mechanical properties of isolated subendocardial and subepicardial cells ffom mouse heart

Supported by the Russia Foundation for Basic Research (14-01-00885, 14-01-31134, 13-04-00365) and JSPS KAKENHI2628212

Assessment of contractility in intact ventricular cardiomyocytes using the dimensionless ‘Frank–Starling Gain’ index

This paper briefly recapitulates the Frank–Starling law of the heart, reviews approaches to establishing diastolic and systolic force–length behaviour in intact isolated cardiomyocytes, and introduces a dimensionless index called ‘Frank–Starling Gain’, calculated as the ratio of slopes of end-systolic and end-diastolic force–length relations. The benefits and limitations of this index are illustrated on the example of regional differences in Guinea pig intact ventricular cardiomyocyte mechanics. Potential applicability of the Frank–Starling Gain for the comparison of cell contractility changes upon stretch will be discussed in the context of intra- and inter-individual variability of cardiomyocyte properties