Parallel Compartments Research Articles

Development of a 4D Digital Phantom for Tracer Kinetic Modeling and Analysis of Dynamic Perfusion PET and SPECT Simulation Studies.

The goal is to develop a 4D digital perfusion cardiac-torso (PCAT) phantom, a tracer kinetic extension of the XCAT phantom, by modeling the time activity curves (TACs) of individual organ regions in the phantom for dynamic perfusion PET and SPECT simulation studies. The PCAT phantom is based on a generalized compartmental model, which accepts the blood input function, multiple series or parallel compartments, the bidirectional rate constants between the compartments, the blood volume in the tissue, the extraction curves, and other properties of a specific tracer. Based on the kinetic differential equations of the compartmental model, the TACs of the targeted organ regions were determined. For a specific time point, a voxelized anatomical realistic phantom, which with or without the cardiac and respiratory motions, was generated and the activity concentrations in the organ regions were assigned according to the corresponding TACs. According to the dynamic scanning protocol, multiple phantoms at different acquisition time points, which could have uniform or non-uniform time intervals, were generated. When combining the dynamic phantoms with realistic projection simulator, realistic dynamic projection data could be generated by easily adopting to various scanning protocols and imaging systems. With the availability of the "known truth", the activity map of the targeted organ regions, the TACs, the estimated rate constants and other kinetic parameters, from the projection data and the reconstructed images could be quantitatively evaluated. We demonstrate the usefulness of the 4D PCAT phantom in initial simulation studies in dynamic myocardial perfusion PET imaging with different tracers. The PCAT phantom was found to be an important bridge between the creation of TACs and the generation of simulated projection data. It is a useful simulation tool to study different kinetic analysis methods, acquisition protocols, reconstruction methods, and imaging parameter settings.

A pilot study investigating the effects of yakult fermented milk drink (L. casei Shirota) on salivary IFN-γ, sIgA, IgA1 and IgA2 in healthy volunteers

This pilot study investigated the effects on salivary cytokine and sIgA before and after daily consumption of Lactobacillus casei Shirota (LcS) in nine healthy adult volunteers. Subjects were asked to consume two bottles each day of a fermented milk drink containing a total of 1.3 · 1010 live cells of LcS (Yakult), for 4 weeks. Volunteers were asked to avoid food and drink for at least 1 h before morning unstimulated saliva samples were collected over a 5 min period. Samples were collected at baseline, at week 1, 2 and 4 of LcS consumption, and 2 weeks after cessation of consumption. We found a significant transient increase in salivary IFN-g levels, but were unable to detect IL-12, and an increase in salivary sIgA, IgA1 and IgA2 secretion. Baseline salivary IFN-g was below the assay detection limits. However, at week 1, 4/9 subjects had detectable salivary IFN-g levels, 8/9 (P<0.01) at week 2 and 3/9 at week 4. None had detectable IFN-g levels at week 6. IFN-g concentrations ranged from 35.3 to 92.0 pg/ml. There was a significant (P<0.02) increase in salivary sIgA secretion rate at week 4 (Fig. A). At week 6, the sIgA secretion rate was greater than baseline. The IgA1 secretion rate was significantly greater than baseline at week 4 (P<0.05) and week 6 (P<0.02) (Fig. B). The IgA2 secretion was also significantly increased at week 4 (P<0.05) and week 6 (P<0.01) (Fig. B) and the IgA1:IgA2 ratio significantly greater at week 2 (P<0.01). This pilot study demonstrates that LcS can induce increased salivary IFN-g, sIgA, IgA1 and IgA2 secretion in healthy adults, which may improve mucosal immunity in the upper respiratory tract and provide health related benefits. A larger detailed study investigating cytokine networks, immunoglobulins and T cell responses in different immune system compartments in parallel with a placebo control group would define more rigorously and precisely the immunological effects of LcS (Yakult).

Advantages in multiplex and live-cell imaging using the CELLview™ cell culture dish

Advantages in multiplex and live-cell imaging using the CELLview™ cell culture dish

Assessment of dermal absorption by thermogravimetric analysis: Development of a diffusion model based on Fick's second law

Recent work in our laboratory shows that it is possible to reproducibly measure the weight change over time of a piece of porcine skin exposed to a chemical vapor by thermogravimetric analysis (TGA), that is, using a microbalance maintained at constant temperature and humidity. Here, we develop a diffusion model by which the TGA skin weight curve can be interpreted. A TGA-specific analytical solution for Fick's second law of diffusion was derived. The solution contains two chemical-dependent parameters; a diffusion coefficient (D) and a skin/air partition coefficient (P). The resulting function was fitted to weight curves from 83 experiments with 4 chemicals; n-butyl acetate, methanol, 2-propanol, and toluene. In most experiments, a single weight function could not adequately describe the shape of the weight curve, therefore up to five parallel compartments, each with its parameter set Di and Pi, were tested. A two-compartment model was adequate for 58% of the experiments according to the Akaike Information Criterion. Dermal penetration of the chemicals was also measured with Franz diffusion cells. The diffusion coefficients obtained by the two methods agreed well. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4365–4375, 2009

Structure-Tunable Bidirectional Hybrid Nanowires via Multicompartment Cylinders

We present structure-tunable bidirectional inorganic-organic hybrid nanowires templated by soft multicompartment cylinders, possessing perfectly parallel compartments. The poly(2-vinylpyridine) compartments are used to bind nanoparticles via supramolecular coordination. The resulting hybrid nanowires are tunable in terms of the distribution of the inorganics in the corona. The two limiting cases are (a) perfectly aligned, parallel nanowires and (b) nanowires with one homogeneous corona. This approach demonstrates how advances in polymer architectures can be used to create novel hybrid materials of unprecedented complexity and very desirable architecture.

Determination of the refractive index and the chiral parameter of a chiral solution based on chiral reflection equations and heterodyne interferometry

This study develops a method for determining the chiral parameter and the refractive index of an isotropic chiral medium using chiral reflection equations and critical angle phenomena. Linearly polarized light propagates back and forth in a parallelogram prism between two parallel compartments with chiral solutions. A beam splitter then divides the light that emerges from the prism into a reflected light beam and a transmitted light beam. The two beams pass through a compensator and an analyzer, respectively, to cause phase compensation and interference of s and p polarizations. The phase difference between the two interference signals are initially optimized by a suitable optical arrangement and subsequently measured by heterodyne interferometry. Additionally, the refractive index of the solution is determined from the critical angle that occurred at the discontinuity of the phase difference between the two interference signals. These results are substituted into derived equations to calculate the chiral parameter. The approach has the merits of both common-path interferometry and heterodyne interferometry.

Behavioural responses of the Persian sturgeon (Acipenser persicus) juveniles to free amino acid solutions

This study analysed the attraction/avoidance responses of the Persian sturgeon (Acipenser persicus) juveniles to 20 free L-amino acid solutions, 0.001 M. We used aquaria with two parallel compartments with a water flow of ≈ 300 mL min−1 in each compartment. During each trial, the flow of clean water in one compartment was replaced for 3 min by a test solution of free amino acids. We counted the number of fish in each compartment every 30 s for 3 min and also used a qualitative assessment to characterise the sturgeon's searching behaviour. Daphnia water extracts were used as a positive control. Treatments and positive and negative controls (clean water) were replicated 10 times each. Solutions of alanine and glycine elicited the strongest food searching responses. This was confirmed by comparing the numbers of fish in test and control compartments. Leucine, histidine, cysteine, isoleucine and proline evoked low positive responses, which were confirmed by a quantitative assessment. Aspartic acid, tyrosine and glutamic acid evoked negative responses. The highest negative effects were evoked by glutamic acid. Therefore, alanine and glycine can be considered as attractants and glutamic acid as a repellent for Persian sturgeon juveniles.

A new class of biophysical models for predicting the probability of decompression sickness in scuba diving

Interconnected compartmental models have been used for decades in physiology and medicine to account for the observed multi-exponential washout kinetics of a variety of solutes (including inert gases) both from single tissues and from the body as a whole. They are used here as the basis for a new class of biophysical probabilistic decompression models. These models are characterized by a relatively well-perfused, risk-bearing, central compartment and one or two non-risk-bearing, relatively poorly perfused, peripheral compartment(s). The peripheral compartments affect risk indirectly by diffusive exchange of dissolved inert gas with the central compartment. On the basis of the accuracy of their respective predictions beyond the calibration regime, the three-compartment interconnected models were found to be significantly better than the two-compartment interconnected models. The former, on the basis of a number of criteria, was also better than a two-compartment parallel model used for comparative purposes. In these latter comparisons, the models all had the same number of fitted parameters (four), were based on linear kinetics, had the same risk function, and were calibrated against the same dataset. The interconnected models predict that inert gas washout during decompression is relatively fast, initially, but slows rapidly with time compared with the more uniform washout rate predicted by an independent parallel compartment model. If empirically verified, this may have important implications for diving practice.

A Pharmacodynamic Turnover Model Capturing Asymmetric Circadian Baselines of Body Temperature, Heart Rate and Blood Pressure in Rats: Challenges in Terms of Tolerance and Animal-handling Effects

This study presents development and behaviour of a feedback turnover model that mimics asymmetric circadian oscillations of body temperature, blood pressure and heart rate in rats. The study also includes an application to drug-induced hypothermia, tolerance and handling effects. Data were collected inn normotensive Sprague-Dawley rats, housed at 25 degrees C with a 12:12 hr light dark cycle (light on at 06:00 am) and with free access of food and water. The model consisted of two intertwined parallel compartments which captured a free-running rhythm with a period close to but not exactly 24 hrs. The free-running rhythm was synchronised to exactly 24 hrs by the environmental timekeeper (12:12 hr light on/off cycle) in experimental settings. The baseline model was fitted to a standardised 24-hr period derived from mean data of six animals over a period of nine consecutive days. The first-order rate constants related to the turnover of the baseline temperature, alpha and beta, were 0.026 min(-1) (+/-5%) and 0.0037 min(-1) (+/-3%). The alpha and beta parameters are approximately 2/transition time between day and night and 2/night time, respectively. The day:night timekeeper g(t), reference point T(ref) and amplitude were 0.053(+/-2%), 37.3(+/-0.02%) and 3.3% (+/-2%), respectively. Simulations with the baseline model revealed stable oscillations (free-running rhythm) in the absence of the timekeeper. This temperature-time profile was then symmetric and had a smaller amplitude, with a slightly shorter period and less pronounced temperature shift as compared to the profile in the presence of an external Timekeeper. Fitting the model to 96 hr mean profiles of blood pressure and heart rate from 10 control animals demonstrated the usefulness of the model. Simulations of the integrated temperature model succeeded in mimicking other modes of administration such as oral dosing.

Expression of constitutively active p21H-rasval12 in postmitotic pyramidal neurons results in increased dendritic size and complexity.

The small G protein p21Ras is a critical molecular switch for relaying neurotrophic actions and is essential for normal functioning and plasticity of the nervous system. In this study, the morphogenetic effects of p21Ras were investigated on neurons in vivo. Morphological changes of layers II/III and Vb commissural pyramidal neurons of the primary somatosensory cortex were analyzed in transgenic mice expressing permanently active p21H-RasVal12 in postmitotic neurons. Pyramidal cells were retrogradely labelled with biotinylated dextran amine and subsequently traced using Neurolucida. Compared with wild-type mice, transgenic animals showed a significant increase in the surface area and volume of basal dendrites on the proximal and intermediate segments in layers II/III and on further distal segments in layer V. In addition, the surface area and volume of the trunk and of the proximal segments of oblique branches of apical dendrites were enlarged in both layers. Sholl analyses of basal and apical dendrites showed a significant increase in dendritic complexity of layer V neurons. A positive correlation was observed between the size of the basal dendrite and the neuronal soma size in the transgenic population, indicating that growth-promoting effects of p21H-RasVal12 affect both cellular compartments in parallel. However, the dendritic surface correlated with the number of tips and dendritic stem diameter in both wild-type and transgenic populations, demonstrating that these relations represent rather conservative design principles in dendritic morphology. The data presented here suggest an important role of p21Ras-dependent signaling in the final differentiation and maintenance of dendritic morphology.

Water and mass budgets of a vertical-flow constructed wetland used for wastewater treatment

To estimate the nutrient and organic matter (Biological Oxygen Demand (BOD 5) and Chemical Oxygen Demand (COD)) removal capacity of a constructed vertical-flow wetland in The Netherlands, a water and nutrient budget study was conducted. Also bacterial water quality enhancement was measured. The system had a Phragmites australis vegetation and comprised four parallel compartments of 0.25 ha each, which were loaded sequentially with sewage from recreational facilities. Annual loading rates were moderate and were estimated to be 16 700 kg COD ha −1; 6700 kg BOD 5 ha −1; 2400 kg N ha −1; and 335 kg P ha −1. The removal efficiencies for COD (81%) and BOD 5 (96%) were high. Almost all Escherichia coli and F-specific RNA bacteriophages (>99%) were removed from the wastewater during transport. The removal efficiencies for nitrogen (30%) and phosphorus (24%) were much lower. Nutrient removal was the result of plant uptake and harvesting (15% of total N input, 10% of total P input), denitrification (8% of total N input), sedimentation and accumulation of organic matter in the soil (7% of N total input, 14% of total P input). Removal efficiencies for N and P could be increased by harvesting the Phragmites vegetation in October, rather than the current harvesting practice in December. This vertical-flow wetland appeared to be P-saturated after 15 years of operation. The use of sandy sediments with better P-adsorbing properties is advocated as a critical issue for the design of these systems. Further, the groundwater eutrophication resulting from the poor functioning of the drainage systems has shown that a good hydraulic separation of vertical-flow systems from the subsurface is an important prerequisite for their proper functioning.

Dependence of intrapulmonary pressure amplitudes on respiratory mechanics during high-frequency oscillatory ventilation in preterm lambs.

In the healthy animal lung, high-frequency oscillatory ventilation (HFOV) achieves effective ventilation at tidal volumes (V(T)) less than or equal to dead space while generating very small pressure fluctuations in the alveolar spaces (deltaP(A)). We hypothesized that the respiratory mechanical parameters influence the magnitude of the intrapulmonary pressure fluctuations during HFOV. A computer model of the neonatal respiratory system was used to examine the independent effects of altering the compliance, nonlinear and linear resistance, and inertance of the respiratory system on V(T), and cyclic intrapulmonary pressures under homogeneous and heterogeneous conditions. The impact of low compliance on the transmission of pressure from the airway opening to the trachea (deltaP(tr)/deltaP(ao)) and alveolar compartment (deltaP(A)/deltaP(ao)) during HFOV was determined in a preterm lamb lung model. In the computer model, an increase in flow-dependent resistance to simulate changing the internal diameter of the tracheal tube from 4.0 mm to 2.5 mm halved the transmission of the pressure waveform to both the carina and the alveolar compartment. Increased peripheral resistance was associated with an increased deltaP(tr)/deltaP(ao) but a reduction in deltaP(A)/deltaP(ao). The deltaP(A)/deltaP(ao) also decreased with increasing alveolar compartment compliance, a finding that was verified in the preterm lamb lung. There was an exponential decrease in the magnitude of deltaP(A1) compared with deltaP(A2) as the ratio of the time constants of the two parallel compartments (tau(1)/tau(2)) increased in the heterogeneous computer lung model. The transmission of driving pressure amplitude to both the proximal airways and lung tissue during HFOV is dependent on lung mechanics and may be greater in the poorly compliant lung than that observed previously in experiments on healthy animals.

Dependence of Intrapulmonary Pressure Amplitudes on Respiratory Mechanics during High-Frequency Oscillatory Ventilation in Preterm Lambs

In the healthy animal lung, high-frequency oscillatory ventilation (HFOV) achieves effective ventilation at tidal volumes (VT) less than or equal to dead space while generating very small pressure fluctuations in the alveolar spaces (ΔPA). We hypothesized that the respiratory mechanical parameters influence the magnitude of the intrapulmonary pressure fluctuations during HFOV. A computer model of the neonatal respiratory system was used to examine the independent effects of altering the compliance, nonlinear and linear resistance, and inertance of the respiratory system on VT, and cyclic intrapulmonary pressures under homogeneous and heterogeneous conditions. The impact of low compliance on the transmission of pressure from the airway opening to the trachea (ΔPtr/ΔPao) and alveolar compartment (ΔPA/ΔPao) during HFOV was determined in a preterm lamb lung model. In the computer model, an increase in flow-dependent resistance to simulate changing the internal diameter of the tracheal tube from 4.0 mm to 2.5 mm halved the transmission of the pressure waveform to both the carina and the alveolar compartment. Increased peripheral resistance was associated with an increased ΔPtr/ΔPao but a reduction in ΔPA/ΔPao. The ΔPA/ΔPao also decreased with increasing alveolar compartment compliance, a finding that was verified in the preterm lamb lung. There was an exponential decrease in the magnitude of ΔPA1 compared with ΔPA2 as the ratio of the time constants of the two parallel compartments (τ1/τ2) increased in the heterogeneous computer lung model. The transmission of driving pressure amplitude to both the proximal airways and lung tissue during HFOV is dependent on lung mechanics and may be greater in the poorly compliant lung than that observed previously in experiments on healthy animals.

A three-compartment model of osmotic water exchange in the lung microvasculature.

A bolus injection of hypertonic NaCl into the pulmonary arterial circulation of an isolated perfused dog lung causes the osmotic movement of water first into, and then out of the capillary. The associated changes in blood constituent concentrations and density are referred to as the osmotic transient (OT). Measurement of the sound conduction velocity of effluent blood during an OT is a highly sensitive way to monitor water movement between the vascular and extravascular spaces. It was our objective to develop a mathematical model that adequately describes this transient change in the sound conduction velocity and evaluate its application under conditions of homogeneous and heterogeneous capillary flow distributions. The model accounts for osmotic water exchange between the capillary and two parallel extravascular compartments, and includes as parameters the osmotic conductances (sigmaK1 ,sigmaK2) of the two compartments. The osmotic conductance parameters incorporate the filtration coefficient for water and reflection coefficient for salt for the two pathways of water exchange. The partition of total extravascular lung water (EVLW) between the two extravascular compartments is a third parameter of the model. The homogeneous model parameter estimates (per gram wet lung weight +/-95% confidence limits) from the best-fit analysis of a typical curve were sigmaK1=2.15 +/-0.07, sigmaK2 = 0.03 + 0.00 [ml h(-1) (mosmol/liter)(-1) g(-1)] and V1 = 23.83+/-0.12 ml, with a coefficient of variation (CV) of 0.08. The heterogeneous parameter estimates for a capillary transit time distribution with mean transit time (MTTc) = 1.72 s, and relative dispersion (RDc) = 0.35 were KI = 2.38+/-0.05, or K2 = 0.03+/-0.00 [ml h(-1) (mosmol/liter)(-1) g(-1)], V1 = 23.91+/-0.08 ml, and CV=0.05. EVLW was 42.1 ml for both models. We conclude that the three-compartment mathematical model adequately describes a typical OT under both homogeneous and heterogeneous blood flow assumptions.

Modelling the kinetics of water loss during potato frying with a compartmental dynamic model

The complexity of the frying process impairs the development of mechanistic models to describe water losses. Empirical models, though lacking a theoretical basis, may provide a suitable and simpler alternative. In this work it was found that a two parallel compartments model (core and edge compartments), with a time-dependent boundary condition, could be successfully applied for this purpose. The model showed a good fit to the experimental data for a variety of experimental conditions tested: potato geometry and size, temperature, oil type and oil use. The core compartment was found to contain about 63% of the initial potato water content. The rate constants of two-compartments were very sensitive to slice thickness, whereas temperature affected only the rate constant of the core compartment. No significant effects were detected in terms of oil type or oil use.

Stimulation of Neonatal and Adult Brain Neurogenesis by Subcutaneous Injection of Basic Fibroblast Growth Factor

Mounting evidence indicates that extracellular factors exert proliferative effects on neurogenetic precursors in vivo. Recently we found that systemic levels of basic fibroblast growth factor (bFGF) regulate neurogenesis in the brain of newborn rats, with factors apparently crossing the blood-brain barrier (BBB) to stimulate mitosis. To determine whether peripheral bFGF affects proliferation during adulthood, we focused on regions in which neurogenesis persists into maturity, the hippocampus and the forebrain subventricular zone (SVZ). In postnatal day 1 (P1) rats, 8 hr after subcutaneous injection (5 ng/gm body weight), bFGF increased [(3)H]thymidine incorporation 70% in hippocampal and SVZ homogenates and elicited twofold increases in mitotic nuclei in the dentate gyrus and the dorsolateral SVZ, detected by bromodeoxyuridine immunohistochemistry. Because approximately 25% of proliferating hippocampal cells stimulated in vivo expressed neuronal traits in culture, bFGF-induced mitosis may reflect increased neurogenesis. bFGF effects were not restricted to the perinatal period; hippocampal DNA synthesis was stimulated by peripheral factor in older animals (P7-P21), indicating the persistence of bFGF-responsive cells and activity of peripheral bFGF into late development. To begin defining underlying mechanisms, pharmacokinetic studies were performed in P28 rats; bFGF transferred from plasma to CSF rapidly, levels rising in both compartments in parallel, indicating that peripheral factor crosses the BBB during maturity. Consequently, we tested bFGF in adults; peripheral bFGF increased the number of mitotic nuclei threefold in the SVZ and olfactory tract, regions exhibiting persistent neurogenesis. Our observations suggest that bFGF regulates ongoing neurogenesis via a unique, endocrine-like pathway, potentially coordinating neuron number and body growth, and potentially providing new approaches for treating damaged brain during development and adulthood.

Nucleoid partitioning and the later stages of sporulation septum synthesis are closely associated events in the sporulating hyphae ofStreptomyces carpinensis

During spore formation in streptomycetes numerous nucleoids are partitioned into uninucleoid compartments in parallel with the multiple septation of the hypha. Electron microscopic observations of sporulating hyphae of Streptomyces carpinensis showing defects in sporulation septum synthesis revealed a close association between chromosome partitioning and the later stages of septum formation.

Nucleoid partitioning and the later stages of sporulation septum synthesis are closely associated events in the sporulating hyphae of Streptomyces carpinensis

During spore formation in streptomycetes numerous nucleoids are partitioned into uninucleoid compartments in parallel with the multiple septation of the hypha. Electron microscopic observations of sporulating hyphae of Streptomyces carpinensis showing defects in sporulation septum synthesis revealed a close association between chromosome partitioning and the later stages of septum formation.

Dosimetry of [15O]water: A physiologic approach

Earlier dosimetry estimates for [15O]water assumed its instantaneous equilibrium with total body water. This assumption leads to an underestimation of the absorbed doses to organs with high blood flows, since the biodistribution of this short-lived radiopharmaceutical is dependent upon blood flow to organs. We have developed a physiologically based whole body blood flow model (WBBFM) using a commercially available icon-driven mathematical simulation software package and applied it to the reevaluation of [15O]water dosimetry in humans. The WBBFM uses multiple parallel compartments to represent organs, heart chambers, the injection site for [15O]water, and blood sampling sites (arterial and venous). Input values to the WBBFM include organ blood flows, organ masses, organ water volumes, organ:blood partition coefficients, injected activity and S-values of [15O]. The WBBFM is based on the same assumptions that are used in calculating regional blood flow using [15O]water and simulates the human body closely in its physiologic response. The activity in each organ is derived from the simulation and is used to calculate absorbed doses. The WBBFM calculated absorbed doses in microGy/MBq (mrad/mCi) to various organs are as follows: heart--2.66 (9.84), kidneys--2.20 (8.15), thyroid--1.83 (6.78), brain--1.66 (6.13), ovaries--1.25 (4.61), breast--1.24 (4.59), and small intestine--1.03 (3.83). These values are approximately two- to threefold higher than the earlier estimates of Kearfott [J. Nucl. Med. 23, 1031-1037 (1982)] and similar to the recent findings of Herscovitch et al. [J. Nucl. Med. 34, 155P (1983)]. We believe this approach yields more realistic dosimetry estimates for [15O]water. Accordingly, we have revised the amount of [15O]water administered during regional blood flow studies at our institution. The relative ease and accuracy of this approach suggests its usefulness in dosimetry estimation for other freely diffusible radiopharmaceuticals.

Effect of perfusion pressure on diastolic stress-strain relations of isolated rat papillary muscle

The effect of perfusion on diastolic muscle properties was investigated in six isolated right ventricular papillary muscles from rat hearts perfused with a crystalloid solution via the septal artery. Stress-strain relations were obtained at different perfusion pressures. Increased perfusion pressure caused an increase of stress at large strains but a decrease of stress at low strains. Thus stress-free strain increased with increasing perfusion pressure. Stress-strain relations of a given muscle at different perfusion pressures (range 12-122 cmH2O) intersected at a single "crossover" strain. Muscle stiffness, defined as the slope of the stress-strain relation, increased at all strains. Muscle diameter measurements indicated that the observed changes of the stress-strain relation occurred in association with vascular filling rather than with formation of edema. To explain the findings, the papillary muscle was modeled by two parallel compartments: muscle cells (together with the extracellular matrix) and vasculature. Perfusion was assumed to have an effect on the axial vascular properties but not on muscle cells. Combination of the stress-strain data of the muscle compartment and the vascular compartment (taken from literature) predicted stress-strain relations similar to those obtained in our perfused papillary muscles. We conclude that increased muscle stiffness at increased perfusion pressure is mainly caused by pressure-dependent changes in mechanical behavior of the vascular compartment.