Affective Adaptation to Repeated SIT and MICT Protocols in Insulin-Resistant Subjects

Introduction The aim of this study was to investigate affective responses to repeated sessions of sprint interval training (SIT) in comparison with moderate-intensity continuous training (MICT) in insulin-resistant subjects.Methods Twenty-six insulin-resistant adults (age, 49 (4) yr; 10 women) were randomized into SIT (n = 13) or MICT (n = 13) groups. Subjects completed six supervised training sessions within 2 wk (SIT session, 4-6 x 30 s all-out cycling/4-min recovery; MICT session, 40-60 min at 60% peak work load). Perceived exertion, stress, and affective state were assessed with questionnaires before, during and after each training session.Results Perceived exertion, displeasure, and arousal were higher during the SIT compared with MICT sessions (all P 0.05).Conclusions The perceptual and affective responses are more negative both during and acutely after SIT compared with MICT in untrained insulin-resistant adults. These responses, however, show significant improvements already within six training sessions, indicating rapid positive affective and physiological adaptations to continual exercise training, both SIT and MICT. These findings suggest that even very intense SIT is mentally tolerable alternative for untrained people with insulin resistance

Intramyocellular lipid accumulation after sprint interval and moderate-intensity continuous training in healthy and diabetic subjects

The effects of sprint interval training (SIT) on intramyocellular (IMCL) and extramyocellular (EMCL) lipid accumulation are unclear. We tested the effects of SIT and moderate-intensity continuous training (MICT) on IMCL and EMCL accumulation in a randomized controlled setting in two different study populations; healthy untrained men (n 28) and subjects with type 2 diabetes (T2D) or prediabetes (n 26). Proton magnetic resonance spectroscopy (H-1 MRS) was used to determine IMCL and EMCL in the Tibialis anterior muscle (TA) before and after a 2-week exercise period. The exercise period comprised six sessions of SIT or MICT cycling on a cycle ergometer. IMCL increased after SIT compared to MICT (P = 0.042) in both healthy and T2D/prediabetic subjects. On EMCL the training intervention had no significant effect. In conclusion, IMCL serves as an important energy depot during exercise and can be extended by high intensity exercise. The effects of high intensity interval exercise on IMCL seem to be similar regardless of insulin sensitivity or the presence of T2D

Sprint interval training decreases left-ventricular glucose uptake compared to moderate-intensity continuous training in subjects with type 2 diabetes or prediabetes

Type 2 diabetes mellitus (T2DM) is associated with reduced myocardial glucose uptake (GU) and increased free fatty acid uptake (FFAU). Sprint interval training (SIT) improves physical exercise capacity and metabolic biomarkers, but effects of SIT on cardiac function and energy substrate metabolism in diabetic subjects are unknown. We tested the hypothesis that SIT is more effective than moderate-intensity continuous training (MICT) on adaptations in left and right ventricle (LV and RV) glucose and fatty acid metabolism in diabetic subjects. Twenty-six untrained men and women with T2DM or prediabetes were randomized into two-week-long SIT (n = 13) and MICT (n = 13) interventions. Insulin-stimulated myocardial GU and fasted state FFAU were measured by positron emission tomography and changes in LV and RV structure and function by cardiac magnetic resonance. In contrast to our hypothesis, SIT significantly decreased GU compared to MICT in LV. FFAU of both ventricles remained unchanged by training. RV end-diastolic volume (EDV) and RV mass increased only after MICT, whereas LV EDV, LV mass, and RV and LV end-systolic volumes increased similarly after both training modes. As SIT decreases myocardial insulin-stimulated GU compared to MICT which may already be reduced in T2DM, SIT may be metabolically less beneficial than MICT for a diabetic heart

Finite Element Analysis of Bone and Experimental Validation

This chapter describes the application of the finite element (FE) method to bone tissues. The aspects that differ the most between bone and other materials’ FE analysis are the type of elements used, constitutive models, and experimental validation. These aspects are looked at from a historical evolution stand point. Several types of elements can be used to simulate similar bone structures and within the same analysis many types of elements may be needed to realistically simulate an anatomical part. Special attention is made to constitutive models, including the use of density-elasticity relationships made possible through CT-scanned images. Other more complex models are also described that include viscoelasticity and anisotropy. The importance of experimental validation is discussed, describing several methods used by different authors in this challenging field. The use of cadaveric human bones is not always possible or desirable and other options are described, as the use of animal or artificial bones. Strain and strain rate measuring methods are also discussed, such as rosette strain gauges and optical devices.publishe

Impact of Sarcoplasmic Reticulum Calcium Release on Calcium Dynamics and Action Potential Morphology in Human Atrial Myocytes: A Computational Study

Electrophysiological studies of the human heart face the fundamental challenge that experimental data can be acquired only from patients with underlying heart disease. Regarding human atria, there exist sizable gaps in the understanding of the functional role of cellular Ca2+ dynamics, which differ crucially from that of ventricular cells, in the modulation of excitation-contraction coupling. Accordingly, the objective of this study was to develop a mathematical model of the human atrial myocyte that, in addition to the sarcolemmal (SL) ion currents, accounts for the heterogeneity of intracellular Ca2+ dynamics emerging from a structurally detailed sarcoplasmic reticulum (SR). Based on the simulation results, our model convincingly reproduces the principal characteristics of Ca2+ dynamics: 1) the biphasic increment during the upstroke of the Ca2+ transient resulting from the delay between the peripheral and central SR Ca2+ release, and 2) the relative contribution of SL Ca2+ current and SR Ca2+ release to the Ca2+ transient. In line with experimental findings, the model also replicates the strong impact of intracellular Ca2+ dynamics on the shape of the action potential. The simulation results suggest that the peripheral SR Ca2+ release sites define the interface between Ca2+ and AP, whereas the central release sites are important for the fire-diffuse-fire propagation of Ca2+ diffusion. Furthermore, our analysis predicts that the modulation of the action potential duration due to increasing heart rate is largely mediated by changes in the intracellular Na+ concentration. Finally, the results indicate that the SR Ca2+ release is a strong modulator of AP duration and, consequently, myocyte refractoriness/excitability. We conclude that the developed model is robust and reproduces many fundamental aspects of the tight coupling between SL ion currents and intracellular Ca2+ signaling. Thus, the model provides a useful framework for future studies of excitation-contraction coupling in human atrial myocytes

Balance between sodium and calcium currents underlying chronic atrial fibrillation termination: An in silico intersubject variability study

BACKGROUND Atrial remodeling as a result of long-standing persistent atrial fibrillation (AF) induces substrate modifications that lead to different perpetuation mechanisms than in paroxysmal AF and a reduction in the efficacy of antiarrhythmic treatments. OBJECTIVE The purpose of this study was to identify the ionic current modifications that could destabilize reentries during chronic AF and serve to personalize antiarrhythmic strategies. METHODS A population of 173 mathematical models of remodeled human atrial tissue with realistic intersubject variability was developed based on action potential recordings of 149 patients diagnosed with AF. The relationship of each ionic current with AF maintenance and the dynamics of functional reentries (rotor meandering, dominant frequency) were evaluated by means of 3-dimensional simulations. RESULTS Self-sustained reentries were maintained in 126 (73%) of the simulations. AF perpetuation was associated with higher expressions of I-Na and I-caL (P < .01), with no significant differences in the remaining currents. I-caL blockade promoted AF extinction in 30% of these 126 models. The mechanism of AF termination was related with collisions between rotors because of an increase in rotor meandering (1.71 +/- 2.01cm(2)) and presented an increased efficacy in models with a depressed INa (P < .01). CONCLUSION Mathematical simulations based on a population of models representing intersubject variability allow the identification of ionic mechanisms underlying rotor dynamics and the definition of new personalized pharmacologic strategies. Our results suggest that the underlying mechanism of the diverging success of I-caL block as an antiarrhythmic strategy is dependent on the basal availability of sodium and calcium ion channel conductivities.Supported by the Spanish Ministry of Education (FPU2010); the Wellcome Trust Fellowship 100246/Z/12/Z; Universitat Politecnica de Valencia; the Spanish Health Research Fund (PI13/00903); the Spanish Society of Cardiology; the Spanish Ministry of Science; Generalitat Valenciana Grants (ACIF/2013/021); and Innovation (Red RIC, PLE2009-0152). Drs. Rodriguez and Climent are equally contributing senior authors.Liberos Mascarell, A.; Bueno-Orovio, A.; Rodrigo Bort, M.; Ravens, U.; Hernández-Romero, I.; Fernández-Avilés, F.; Guillem Sánchez, MS.... (2016). Balance between sodium and calcium currents underlying chronic atrial fibrillation termination: An in silico intersubject variability study. Heart Rhythm. 13(12):2358-2365. https://doi.org/10.1016/j.hrthm.2016.08.028S23582365131

Subcellular calcium dynamics in a whole-cell model of an atrial myocyte

In this study, we present an innovative mathematical modeling approach that allows detailed characterization of Ca2+ movement within the three-dimensional volume of an atrial myocyte. Essential aspects of the model are the geometrically realistic representation of Ca2+ release sites and physiological Ca2+ flux parameters, coupled with a computationally inexpensive framework. By translating nonlinear Ca2+ excitability into threshold dynamics, we avoid the computationally demanding time stepping of the partial differential equations that are often used to model Ca2+ transport. Our approach successfully reproduces key features of atrial myocyte Ca2+ signaling observed using confocal imaging. In particular, the model displays the centripetal Ca2+ waves that occur within atrial myocytes during excitation–contraction coupling, and the effect of positive inotropic stimulation on the spatial profile of the Ca2+ signals. Beyond this validation of the model, our simulation reveals unexpected observations about the spread of Ca2+ within an atrial myocyte. In particular, the model describes the movement of Ca2+ between ryanodine receptor clusters within a specific z disk of an atrial myocyte. Furthermore, we demonstrate that altering the strength of Ca2+ release, ryanodine receptor refractoriness, the magnitude of initiating stimulus, or the introduction of stochastic Ca2+ channel activity can cause the nucleation of proarrhythmic traveling Ca2+ waves. The model provides clinically relevant insights into the initiation and propagation of subcellular Ca2+ signals that are currently beyond the scope of imaging technology