A computational predictor of the anaerobic mechanical power outputs from a clinical exercise stress test.

We previously were able to predict the anaerobic mechanical power outputs using features taken from a maximal incremental cardiopulmonary exercise stress test (CPET). Since a standard aerobic exercise stress test (with electrocardiogram and blood pressure measurements) has no gas exchange measurement and is more popular than CPET, our goal, in the current paper, was to investigate whether features taken from a clinical exercise stress test (GXT), either submaximal or maximal, can predict the anaerobic mechanical power outputs to the same level as we found with CPET variables. We have used data taken from young healthy subjects undergoing CPET aerobic test and the Wingate anaerobic test, and developed a computational predictive algorithm, based on greedy heuristic multiple linear regression, which enabled the prediction of the anaerobic mechanical power outputs from a corresponding GXT measures (exercise test time, treadmill speed and slope). We found that for submaximal GXT of 85% age predicted HRmax, a combination of 3 and 4 variables produced a correlation of r = 0.93 and r = 0.92 with % error equal to 15 ± 3 and 16 ± 3 on the validation set between real and predicted values of the peak and mean anaerobic mechanical power outputs (p < 0.001), respectively. For maximal GXT (100% of age predicted HRmax), a combination of 4 and 2 variables produced a correlation of r = 0.92 and r = 0.94 with % error equal to 12 ± 2 and 14 ± 3 on the validation set between real and predicted values of the peak and mean anaerobic mechanical power outputs (p < 0.001), respectively. The newly developed model allows to accurately predict the anaerobic mechanical power outputs from a standard, submaximal and maximal GXT. Nevertheless, in the current study the subjects were healthy, normal individuals and therefore the assessment of additional subjects is desirable for the development of a test applicable to other populations.

Stretching affects intracellular oxygen levels: three-dimensional multiphysics studies.

Multiphysics modeling is an emerging approach in cellular bioengineering research, used for simulating complex biophysical interactions and their effects on cell viability and function. Our goal in the present study was to integrate cell-specific finite element modeling--which we have developed in previous research to simulate deformation of individual cells subjected to external loading--with oxygen transport in the deformed cells at normoxic and hypoxic environments. We specifically studied individual and combined effects of substrate stretch levels, O2 concentration in the culture media, and temperature of the culture media on intracellular O2 levels in cultured myoblasts, in models of two individual cells. We found that (i) O2 transport became faster with the increasing levels of substrate stretch (ranging from 0 to 24%), and (ii) the effect of a 3 °C temperature drop on slowing down the O2 transport was milder with respect to the effect that strains had. The changes in cell geometry due to externally applied deformations could, hence, theoretically affect cell respiration, which should be a consideration in cellular mechanics experiments.

A simple stochastic model to explain the sigmoid nature of the strain-time cellular tolerance curve.

Using animal and tissue-engineered experimental models, we previously found that a decreasing sigmoidal function is adequate for describing the diminishing tolerance of skeletal muscle tissue/cells for static mechanical strains delivered over time. Compressive loads at the tissue scale, which are associated with weight-bearing, appear to stretch the plasma membrane (PM) of cells at the mesoscopic-microscopic scales. The permeability of such stretched PMs may then increase, which could alter the control mechanisms and consequently the homeostasis of the deformed cells. The present paper is aimed at demonstrating this suggested deformation-diffusion damage pathway - which is particularly relevant to the aetiology of deep tissue injury - at the level of a single cell, using simple stochastic computer modeling which is supported by experimental confocal microscopy imaging data. The modeling and confocal studies better explain the strain-time injury threshold previously proposed by our group, and in particular, they provide an explanation for the nature of the rapid decrease of the threshold curve. The simulations revealed that there was a clear trend of nearly inverse relationship between the level of stretch applied to the PM and the time for accumulation of cytotoxic contents of a diffusing biomolecule. Taken together with the confocal data, which correspondingly demonstrated increased permeability of the PM of statically stretched cells to a fluorescent dye, the present results point to cell-level deformation-diffusion damage as a factor that should be looked at more closely in aetiological research of pressure ulcers.

Prediction of the Wingate anaerobic mechanical power outputs from a maximal incremental cardiopulmonary exercise stress test using machine-learning approach.

The Wingate Anaerobic Test (WAnT) is a short-term maximal intensity cycle ergometer test, which provides anaerobic mechanical power output variables. Despite the physiological significance of the variables extracted from the WAnT, the test is very intense, and generally applies for athletes. Our goal, in this paper, was to develop a new approach to predict the anaerobic mechanical power outputs using maximal incremental cardiopulmonary exercise stress test (CPET). We hypothesized that maximal incremental exercise stress test hold hidden information about the anaerobic components, which can be directly translated into mechanical power outputs. We therefore designed a computational model that included aerobic variables (features), and used a new computational \ predictive algorithm, which enabled the prediction of the anaerobic mechanical power outputs. We analyzed the chosen predicted features using clustering on a network. For peak power (PP) and mean power (MP) outputs, the equations included six features and four features, respectively. The combination of these features produced a prediction model of r = 0.94 and r = 0.9, respectively, on the validation set between the real and predicted PP/MP values (P< 0.001). The newly predictive model allows the accurate prediction of the anaerobic mechanical power outputs at high accuracy. The assessment of additional tests is desired for the development of a robust application for athletes, older individuals, and/or non-healthy populations.

Changes in permeability of the plasma membrane of myoblasts to fluorescent dyes with different molecular masses under sustained uniaxial stretching.

Deep tissue injury (DTI) is a serious pressure ulcer which onsets in skeletal muscle tissues adjacent to weight-bearing bony prominences. Recent literature points at sustained large deformations in muscle tissue, which translate to static stretching of the plasma membrane (PM) at the cell-scale, as the primary cause of accumulated cell death in DTI. It has been specifically suggested that prolonged exposure to large tensional PM strains interferes with normal cellular homeostasis, primarily by affecting transport through the PM which could become more permeable when stretched. In this context, using confocal imaging and fluorescence-activated cell sorter (FACS), we visualized and quantified here the uptake of fluorescent Dextran dye by myoblasts that were statically stretched uniaxially, up to physiological strains of 3%, 6% and 9%, using two different molecular masses for the Dextran (4kDa and 20kDa). The confocal and FACS studies provided consistent evidence that the permeability of the PM increased at large static deformations. Furthermore, the FACS data indicated that the kinetics of the PM permeability very likely depends on the size of the biomolecular marker. Both results were consistent with reports published in the neurotrauma literature on the kinetics of uptake of fluorescent biomolecules by dynamically stretched neurons; hence there are some analogues in the biomechanical pathways of cellular-level injury between DTI and impact insults. The present work provides additional empirical support to the theory of cell-scale deformation-diffusion damage in the etiology of DTI, and may lead to better understanding of time courses for onset of cellular damage in DTI, by exploring mass transport processes across the PM of the involved cells.

The effect of compressive deformations on the rate of build-up of oxygen in isolated skeletal muscle cells.

In this study we integrated between confocal-based cell-specific finite element (FE) modeling and Virtual Cell (VC) transport simulations in order to determine trends of relationship between externally applied compressive deformations and build-up rates of oxygen in myoblast cells, and to further test how mild culture temperature drops (~3°C) might affect such trends. Geometries of two different cells were used, and each FE cell model was computationally subjected to large compressive deformations. Build-up of oxygen concentrations within the deformed cell shapes over time were calculated using the VC software. We found that the build-up of oxygen in the cells was slightly but consistently hindered when compressive cell deformations were applied. Temperature drops characteristic to ischemic conditions further hinder the oxygen built-up in cells. In a real-world condition, a combination of the deformation and temperature factors should be anticipated, and their combined effect might substantially impair cell respiration functions.