Fluid mechanics in the perivascular space

Perivascular space (PVS) within the brain is an important pathway for interstitial fluid (ISF) and solute transport. Fluid flowing in the PVS can affect these transport processes and has significant impacts on physiology. In this paper, we carry out a theoretical analysis to investigate the fluid mechanics in the PVS. With certain assumptions and approximations, we are able to find an analytical solution to the problem. We discuss the physical meanings of the solution and particularly examine the consequences of the induced fluid flow in the context of convection-enhanced delivery (CED). We conclude that peristaltic motions of the blood vessel walls can facilitate fluid and solute transport in the PVS.     

Canine trachealis muscle shortening and cartilage mechanics.

Canine trachealis muscle will shorten by 70% of resting length when maximally stimulated in vitro. In contrast, trachealis muscle will shorten by only 30-40% when stimulated in vivo. To examine the possibility that an elastic load applied by the tracheal cartilage contributes to the in vivo limitation of shortening, single pairs of sonomicrometry crystals were inserted into the trachealis muscle at the level of the fifth cartilage ring in five dogs. The segment containing the crystals was then excised and mounted on a tension-testing apparatus. Points on the active length-tension curve and the passive length-tension relation of the cartilage only were determined. The preload applied to the muscle before contraction varied from 10 to 40 g (mean 21 +/- 4 g). The afterload applied by the cartilage during trachealis contraction ranged from 13 to 56 g (30 +/- 6 g). The calculated elastic afterloads were substantial and appeared to be sufficient to explain the degree of shortening observed in four of the seven rings; in the remaining three rings, the limitation of shortening was greater than would be expected from the elastic load provided by the cartilage. Additional sources of loading and/or additional mechanisms may contribute to limited in situ shortening. In summary, tracheal cartilage applies a preload and an elastic afterload to the trachealis that are substantial and contribute to the limitation of trachealis muscle shortening in vivo.     

Forced vibrations of a circular muscle ring

We consider the small radial displacement of a circular ring of cardiac muscle subjected to periodic forcing. The ring in question is that in the middle layer, at the transverse midsection, of the left ventricle. We show that the ring reacts in a periodic manner when forced in a periodic manner. This is accomplished by writing the differential equation for the ring and solving it for two cases-one for constant and one for variable ring thickness.     

Passive mechanics of muscle tendinous junction of canine diaphragm.

The diaphragmatic muscle tendon is a biaxially loaded junction in vivo. Stress-strain relations along and transverse to the fiber directions are important in understanding its mechanical properties. We hypothesized that 1) the central tendon possesses greater passive stiffness than adjacent muscle, 2) the diaphragm muscle is anisotropic, whereas the central tendon near the junction is essentially isotropic, and 3) a gradient in passive stiffness exists as one approaches the muscle-tendinous junction (MTJ). To investigate these hypotheses, we conducted uniaxial and biaxial mechanical loading on samples of the MTJ excised from the midcostal region of dog diaphragm. We measured passive length-tension relationships of the muscle, tendon, and MTJ in the direction along the muscle fibers as well as transverse to the fibers. The MTJ was slack in the unloaded state, resulting in a J-shaped passive tension-strain curve. Generally, muscle strain was greater than that of MTJ, which was greater than tendon strain. In the muscular region, stiffness in the direction transverse to the fibers is much greater than that along the fibers. The central tendon is essentially inextensible in the direction transverse to the fibers as well as along the fibers. Our data demonstrate the existence of more pronounced anisotropy in the muscle than in the tendon near the junction. Furthermore, a gradient in muscle stiffness exists as one approaches the MTJ, consistent with the hypothesis of continuous passive stiffness across the MTJ.     

Smooth operators. The molecular mechanics of smooth muscle contraction

Smooth muscle cells squeeze the blood back to your heart, raise the hackles on your neck and change the F-stop of your eyes. The past year has provided penetrating new insights into their mechanism of contraction.     

Estimates of cellular mechanics in an arterial smooth muscle.

Estimates of force generation or shortening obtained from smooth muscle tissues are valid for individual cells only if each cell is contracting homogeneously and if cells anatomically arranged in series are mechanically coupled. These two assumptions were tested and shown to be valid for the pig carotid media under certain conditions. Homogeneity of cellular responses in carotid strips was estimated from the motion of markers on the tissue during K+ -induced isometric contractions. When tissues were stretched to L0 (the optimum length for force generation), there was little marker movement on stimulation. However, considerable marker movement was observed on stimulation at shorter muscle lengths, reflecting localized shortening or stretching. The mechanical coupling of the very small cells in the media was determined by measuring the dependence of cell length on tissue length. Tissues were fixed with glutaraldehyde during isometric contractions at various tissue lengths (0.4--1.1 x L0). The fixed tissues were macerated with acid and the lengths of the dispersed cells were measured. Cell lengths were broadly distributed at all muscle lengths. However, the direct proportionality between mean cell length and muscle length (as a fraction of L0) indicated that cells which are anatomically in series are coupled force-transmitting structures. We conclude that valid estimates of cellular mechanical function in this preparation can be obtained from tissue measurements at lengths greater than about 0.9L0.     

A model of inspiratory muscle mechanics

We have previously shown that the costal and crural parts of the diaphragm have different actions on the rib cage (RC) and that the tension developed in one part is not transmitted perfectly to the other. Thus the diaphragm can be modeled pneumatically or electrically as two generators or pumps in series between the lung and abdomen. As such, the force developed by diaphragmatic contraction is the sum of the forces developed in each part, whereas the volume displaced is the same for each part and equal to the total volume displaced. The costal part of the diaphragm is in series with the intercostal and accessory (IA) muscles between the lung and RC, whereas the crural part is in parallel. The volume displaced by simultaneous contraction of the crural part and IA is the sum of volumes displaced by each part. The action of pleural and abdominal pressure [acting through the area of apposition (Aap) of the diaphragm to RC] can be modelled as a summing junction between IA and RC. With hyperinflation the costal part acts more and more in parallel with both IA and the crural part, whereas Aap diminishes, so that the ability to develop large forces decreases independently of the muscles' force-length relationships. The model also predicts that the factors determining the length of the costal and crural parts are different. Finally, the parallel and serial arrangement of the inspiratory musculature allows for increases in maximum power, maximum force, and maximum velocity by appropriate recruitment of the various muscle groups.     

Effect of long-term muscle paralysis on human single fiber mechanics.

This study compared human muscles following long-term reduced neuromuscular activity to those with normal functioning regarding single fiber properties. Biopsies were obtained from the vastus lateralis of 5 individuals with chronic (>3 yr) spinal cord injury (SCI) and 10 able-bodied controls (CTRL). Chemically skinned fibers were tested for active and passive mechanical characteristics and subsequently classified according to myosin heavy chain (MHC) content. SCI individuals had smaller proportions of type I (11 +/- 7 vs. 34 +/- 5%) and IIa fibers (11 +/- 6 vs. 31 +/- 5%), whereas type IIx fibers were more frequent (40 +/- 13 vs. 7 +/- 3%) compared with CTRL subjects (P < 0.05). Cross-sectional area and peak force were similar in both groups for all fiber types. Unloaded shortening velocity of fibers from paralyzed muscles was higher in type IIa, IIa/IIx, and IIx fibers (26, 65, and 47%, respectively; P < 0.01). Consequently, absolute peak power was greater in type IIa (46%; P < 0.05) and IIa/IIx fibers (118%; P < 0.01) of the SCI group, whereas normalized peak power was higher in type IIa/IIx fibers (71%; P < 0.001). Ca(2+) sensitivity and passive fiber characteristics were not different between the two groups in any fiber type. Composite values (average value across all fibers analyzed within each study participant) showed similar results for cross-sectional area and peak force, whereas maximal contraction velocity and fiber power were more than 100% greater in SCI individuals. These data illustrate that contractile performance is preserved or even higher in the remaining fibers of human muscles following reduced neuromuscular activity.     

High-frequency, low-magnitude vibrations suppress the number of blood vessels per muscle fiber in mouse soleus muscle.

Extremely low-magnitude (0.3 g), high-frequency (30-90 Hz), whole body vibrations can stimulate bone formation and are hypothesized to provide a surrogate for the oscillations of muscle during contraction. Little is known, however, about the potential of these mechanical signals to stimulate adaptive responses in other tissues. The objective of this study was to determine whether low-level mechanical signals produce structural adaptations in the vasculature of skeletal muscle. Eight-week-old male BALB/cByJ (BALB) mice were divided into two experimental groups: mice subjected to low-level, whole body vibrations (45 Hz, 0.3 g) superimposed on normal cage activities for 15 min/day (n = 6), and age-matched controls (n = 7). After the 6-wk experimental protocol, sections from end and mid regions of the soleus muscles were stained with lectin from Bandeiraea Simplicifolia, an endothelial cell marker, and smooth muscle (SM) alpha-actin, a perivascular cell marker. Six weeks of this low-level vibration caused a 29% decrease in the number of lectin-positive vessels per muscle fiber in the end region of the soleus muscle, indicating a significant reduction in the number of capillaries per muscle fibers. Similarly, these vibrations caused a 36% reduction in SM alpha-actin-positive vessels per muscle fiber, indicating a reduction in the number of arterioles and venules. The decreases in lectin- and SM alpha-actin-positive vessels per muscle fiber ratios were not significant in the mid muscle sections. These results demonstrate the sensitivity of the vasculature in mouse skeletal muscle to whole body, low-level mechanical signals.     

An ultrasensitive isometric force transducer for single smooth muscle cell mechanics.

The principles of operation, design, and performance of a differential photooptical transducer of very high sensitivity are described. Useful range is 10-2,000 mugf with sufficiently low drift to allow recordings of contractile responses of isolated single smooth muscle cells. Comparison with several previous designs is presented.     

Fluid mechanics,cell distribution,and environment in CellCube bioreactors

Cultivation of MRC-5 cells and attenuated hepatitis A virus (HAV) for the production of VAQTA, an inactivated HAV vaccine (1), is performed in the CellCube reactor, a laminar flow fixed-bed bioreactor with an unusual diamond-shaped, diverging-converging flow geometry. These disposable bioreactors have found some popularity for the production of cells and gene therapy vectors at intermediate scales of operation (2, 3). Early testing of the CellCube revealed that the fluid mechanical environment played a significant role in nonuniform cell distribution patterns generated during the cell growth phase. Specifically, the reactor geometry and manufacturing artifacts, in combination with certain inoculum practices and circulation flow rates, can create cell growth behavior that is not simply explained. Via experimentation and computational fluid dynamics simulations we can account for practically all of the observed cell growth behavior, which appears to be due to a complex mixture of flow distribution, particle deposition under gravity, fluid shear, and possibly nutritional microenvironment.     

Some proposals in cardiac muscle mechanics and energetics

Based on A. V. Hill's three-component model, mechanical properties of the contractile element (CE), such as velocity and tension, were determined as muscle shortening and loads in quick-release or afterloaded isotonic contraction. The method is applicable for studying cardiac mechanics, to obtain force-velocity data of the same CE length at varous afterloads. Analysis of the energetics of cardiac muscle was based on simulation studies of cardiac mechanics (Wong 1971, 1972). By proper derivation, the conventional contractile element work (CEW) was found to be a minor energy determinant. The tension-time integral and tension-independent heat (Ricchiuti and Gibbs, 1965) represent energy utilization for activation and maintenance of tension, the primary energy determinant.     

Chronic intermittent hypoxia alters NE reactivity and mechanics of skeletal muscle resistance arteries.

Although arterial dilator reactivity is severely impaired during exposure of animals to chronic intermittent hypoxia (CIH), few studies have characterized vasoconstrictor responsiveness in resistance arteries of this model of sleep-disordered breathing. Sprague-Dawley rats were exposed to CIH (10% inspired O2 fraction for 1 min at 4-min intervals; 12 h/day) for 14 days. Control rats were housed under normoxic conditions. Diameters of isolated gracilis muscle resistance arteries (GA; 120-150 microm) were measured by television microscopy before and during exposure to norepinephrine (NE) and angiotensin II (ANG II) and at various intraluminal pressures between 20 and 140 mmHg in normal and Ca2+-free physiological salt solution. There was no difference in the ability of GA to constrict in response to ANG II (P = 0.42; not significant; 10(-10)-10(-7) M). However, resting tone, myogenic activation, and vasoconstrictor responses to NE (P < 0.001; 10(-9)-10(-6) M) were reduced in CIH vs. controls. Treatment of rats with the superoxide scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (tempol; 1 mM) in the drinking water restored myogenic responses and NE-induced constrictions of CIH rats, suggesting that elevated superoxide production during exposure to CIH attenuates vasoconstrictor responsiveness to NE and myogenic activation in skeletal muscle resistance arteries. CIH also leads to an increased stiffness and reduced vessel wall distensibility that were not correctable with oral tempol treatment.     

Effect of viscosity on mechanics of single, skinned fibers from rabbit psoas muscle.

Muscle contraction is highly dynamic and thus may be influenced by viscosity of the medium surrounding the myofilaments. Single, skinned fibers from rabbit psoas muscle were used to test this hypothesis. Viscosity within the myofilament lattice was increased by adding to solutions low molecular weight sugars (disaccharides sucrose or maltose or monosaccharides glucose or fructose). At maximal Ca2+ activation, isometric force (Fi) was inhibited at the highest solute concentrations studied, but this inhibition was not directly related to viscosity. Solutes readily permeated the filament lattice, as fiber diameter was unaffected by added solutes (except for an increased diameter with Fi < 30% of control). In contrast, there was a linear dependence upon 1/viscosity for both unloaded shortening velocity and also the kinetics of isometric tension redevelopment; these effects were unrelated to either variation in solution osmolarity or inhibition of force. All effects of added solute were reversible. Inhibition of both isometric as well as isotonic kinetics demonstrates that viscous resistance to filament sliding was not the predominant factor affected by viscosity. This was corroborated by measurements in relaxed fibers, which showed no significant change in the strain-rate dependence of elastic modulus when viscosity was increased more than twofold. Our results implicate cross-bridge diffusion as a significant limiting factor in cross-bridge kinetics and, more generally, demonstrate that viscosity is a useful probe of actomyosin dynamics.     

Skeletal muscle mechanics in osteoporotic and nonosteoporotic postmenopausal women

The purpose of this study was to evaluate single-joint, dynamic muscle function of osteoporotic (OST) and nonosteoporotic (N-OST) women. Knee flexor and extensor function in postmenopausal women (6th decade OST,n = 15; 7th decade OST,n = 10; 6th decade N-OST,n = 6; 7th decade N-OST,n = 5) were evaluated at five angular velocities from 60° · s^–1 to 300° · s^–1. All subject groups had similar anthropometric measurements, but the 6th decade N-OST group were more physically active than the age-matched OST group. The OST and N-OST women produced peak torque at similar knee angles. The 6th decade N-OST women produced significantly greater knee extensor mean peak torque and angle specific torque, and mean work than any of the other three groups (P<0.05). However, knee flexor function was equivalent throughout the groups for most comparisons, except those between the 6th decade N-OST and 7th decade OST. While previous research has shown an early loss of flexor muscle function in ageing women, our data indicated that women with osteoporosis also experience a deterioration in quadriceps muscle function not encountered within the N-OST subjects. It is possible that such a change is precipitated by reduced physical activity, and may mirror deterioration in bone mineral content.     

Electromyography activity of vastus lateralis muscle during whole-body vibrations of different frequencies

The aim of this study was to analyze electromyography (EMG) responses of vastus lateralis muscle to different whole-body vibration frequencies. For this purpose, 16 professional women volleyball players (age, 23.9 +/- 3.6 years; height, 182.5 +/- 11.1 cm; weight, 78.4 +/- 5.6 kg) voluntarily participated in the study. Vibration treatment was administered while standing on a vibrating platform with knees bent at 100 degrees (Nemes Bosco-system, Rome, Italy). EMG root mean square (rms) and was recorded for 60 seconds while standing on the vibrating plate in the following conditions: no vibrations and 30-, 40-, and 50-Hz vibration frequencies in random order. The position was kept for 60 seconds in each treatment condition. EMGrms was collected from the vastus lateralis muscle of the dominant leg. Statistical analysis showed that, in all vibration conditions, average EMGrms activity of vastus lateralis was higher than in the no-vibration condition. The highest EMGrms was found at 30 Hz, suggesting this frequency as the one eliciting the highest reflex response in vastus lateralis muscle during whole-body vibrations in half-squat position. An extension of these studies to a larger population appears worthwhile to further elucidate the responsiveness of the neuromuscular system to whole-body vibrations administered through vibrating platforms and to be able to develop individual treatment protocols.     

Smooth muscle molecular mechanics in airway hyperresponsiveness and asthma

Asthma is a respiratory disorder characterized by airway inflammation and hyperresponsiveness associated with reversible airway obstruction. The relative contributions of airway hyperresponsiveness and inflammation are still debated, but ultimately, airway narrowing mediated by airway smooth muscle contraction is the final pathway to asthma. Considerable effort has been devoted towards identifying the factors that lead to the airway smooth muscle hypercontractility observed in asthma, and this will be the focus of this review. Airway remodeling has been observed in severe and fatal asthma. However, it is unclear whether remodeling plays a protective role or worsens airway responsiveness. Smooth muscle plasticity is a mechanism likely implicated in asthma, whereby contractile filament rearrangements lead to maximal force production, independent of muscle length. Increased smooth muscle rate of shortening via altered signaling pathways or altered contractile protein expression has been demonstrated in asthma and in numerous models of airway hyperresponsiveness. Increased rate of shortening is implicated in counteracting the relaxing effect of tidal breathing and deep inspirations, thereby creating a contracted airway smooth muscle steady-state. Further studies are therefore required to understand the numerous mechanisms leading to the airway hyperresponsiveness observed in asthma as well as their multiple interactions.