John E. Speich, Ph.D.

Split-Tube Flexure

US Patent No. 6,585,445

2003-07-01

Goldfarb, M. and Speich, J., “Split-Tube Flexure,” United States patent number 6,585,445, Issued July 1, 2003.

The Detrusor Tension Sensor: A Model for Novel Cystometrics in Overactive Bladder

NIH - NIDDK $1,656,321

2015-08-20

Urinary urgency is the key symptom in Overactive Bladder (OAB) that occurs during the filling phase of micturition, and increased detrusor wall tension is thought to be a critical factor in the pathophysiology of OAB. However, because pressure increases little during bladder filling and does not reflect changes in detrusor wall tension, true filling phase physiology cannot be evaluated during clinical cystometrics. Thus, objective assessments of OAB using standard clinical cystometric testing are difficult or impossible. Furthermore, evaluation of OAB using verbal sensory thresholds recommended by the International Continence Society are subjective and poorly defined. Thus, there is a pressing need for a mechanistically relevant diagnostic test of OAB that incorporates objective metrics for the direct evaluation of detrusor wall tension. Using a systems model of the filling phase of micturition, the detrusor smooth muscle and its in-series tension sensitive afferent nerves can be represented as a tension sensor with a definable input (volume), a continuously measurable output (urgency), and objectively measurable biomechanical parameters that affect the load on the tension sensor. Based on our previous investigations and the work of others, we have identified the following biomechanical parameters that can directly affect the load on the detrusor tension sensor during filling: bladder geometry, dynamic compliance, and spontaneous rhythmic contractions. In the current proposal, we will develop novel cystometric tests to identify 3 new tension-mediated OAB sub- categories (geometry-mediated, dynamic compliance-mediated, and spontaneous rhythmic contraction mediated) and a non-tension-medicated sub-category due to alterations in nervous system processing. Our new cystometrics will include 1) a sliding scale Urgency Meter that will allow patients to continuously record the tension sensor output of acute urgency, 2) two and three dimensional bladder ultrasonography to provide real- time measurements of bladder geometry that will be used to measure the effect of geometry and used for dynamic compliance calculations, and 3) Fast Fourier Transform (FFT) analysis to objectively measure filling phase spontaneous rhythmic contractions. These new metrics will provide a quantitative mechanistic link between OAB symptomatology and detrusor function, and we will use these new metrics to identify tension- mediated and non-tension mediated sub-groups of OAB.

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Engineering Courses

EGMN 201 Dynamics and Kinematics EGMN 202 Mechanics of Deformables EGMN 300 Mechanical Systems Design EGMN 315 Process and Systems Dynamics ENGR 395 Professional Development ENGR 398 Cooperative Education Experience EGMN 402/403 Senior Design Studio EGMN 427 Robotics EGMN 568 Robot Manipulators

Comparison of 2D and 3D ultrasound methods to measure serial bladder volumes during filling: Steps toward development of non-invasive ultrasound urodynamics

Nagle AS, Bernardo RJ, Varghese J, Carucci LR, Klausner AP, Speich JE.

2018-01-04

Non-invasive methods to objectively characterize overactive bladder (OAB) and other forms of voiding dysfunction using real-time ultrasound are currently under development but require accurate and precise serial measurements of bladder volumes during filling. This study’s objective was to determine the most accurate and precise ultrasound-based method of quantifying serial bladder volumes during urodynamics (UD). Twelve female participants with OAB completed an extended UD procedure with the addition of serial bladder ultrasound images captured once per minute. Bladder volume was measured using three ultrasound methods: (1) Vspheroid: two-dimensional (2D) method calculated assuming spheroid geometry; (2) Vbih: 2D correction method obtained by multiplying Vspheroid by a previously derived correction factor of 1.375; and (3) V3D: three-dimensional (3D) method obtained by manually tracing the bladder outline in six planes automatically reconstructed into a solid rendered volume. These volumes were compared to a control (Vcontrol) obtained by adding UD infused volume and the volume of estimated urine production. Based on linear regression analysis, both Vbih and V3D were fairly accurate estimators of Vcontrol, but V3D was more precise. Vspheroid significantly underestimated Vcontrol. Although the Vbih and V3D methods were more accurate than the more-commonly used Vspheroid method for measuring bladder volumes during UD, the V3D method was the most precise and could best account for non-uniform bladder geometries. Therefore, the V3D method may represent the best tool required for the continued development of non-invasive methods to diagnose OAB and other forms of voiding dysfunction.

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Quantification of bladder wall biomechanics during urodynamics: A methodologic investigation using ultrasound

Anna S. Nagle, Adam P. Klausner, Jary Varghese, Rachel J. Bernardo, Andrew F. Colhoun, Robert W. Barbee, Laura R. Carucci, John E. Speich

2017-08-11

Overactive bladder is often characterized by biomechanical changes in the bladder wall, but there is no established method to measure these changes in vivo. The goal of this study was to develop a novel method to determine detrusor wall biomechanical parameters during urodynamics through the incorporation of transabdominal ultrasound imaging. Individuals with overactive bladder (OAB) underwent ultrasound imaging during filling. The fill rate was 10% of the cystometric capacity per minute as determined by an initial fill. Transabdominal ultrasound images were captured in the midsagittal and transverse planes at 1 min intervals. Using image data and Pves, detrusor wall tension, stress, and compliance were calculated. From each cross − sectional image, luminal and wall areas along with inner perimeters were measured. In the sagittal and transverse planes, wall tension was calculated as Pves ∗ luminal area, wall stress as tension/wall area, and strain as the change in perimeter normalized to the perimeter at 10% capacity. Elastic modulus was calculated as stress/strain in the medial–lateral and cranial-caudal directions. Patient-reported fullness sensation was continuously recorded. Data from five individuals with OAB showed that detrusor wall tension, volume, and strain had the highest correlations to continuous bladder sensation of all quantities measured. This study demonstrates how detrusor wall tension, stress, strain, and elastic modulus can be quantified by adding ultrasound imaging to standard urodynamics. This technique may be useful in diagnosing and better understanding the biomechanics involved in OAB and other bladder disorders.

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Effects of vesical & perfusion pressure on perfusate flow, & flow on vesical pressure, in the isolated perfused working pig bladder reveal a potential mechanism for regulation of detrusor compliance

Vince, R., Tracey, A., Deebel, N., Barbee, R., Speich, J., Klausner, A. and Ratz, P.

2017-07-26

Although there is evidence that deficits in bladder blood flow negatively impact bladder function, the effects of vesical, and perfusion pressures on bladder perfusion (perfusate flow), and of perfusate flow on vesical pressure, remain poorly understood. The present study used the isolated perfused working pig bladder model to examine the relationships between blood flow, and vesical and perfusion pressures. Vesical arteries of pig bladders obtained from a local slaughterhouse were cannulated and perfused with Krebs-Henseleit solution at different pressures, and with carbachol to cause bladder contraction. The urethra of each bladder was cannulated to permit filling (10 mL/min), isovolumetric contraction and emptying. A ureter was cannulated with a pressure sensor to monitor vesical pressure. When at rest (50 mL vesical volume), bladder vesical pressure was 8.06 ± 1.5 mmHg and perfusate flow driven by a pressure gradient of 105 mmHg was 22.5 ± 2 mL/min (58.9 ± 7.8 mL/min-100 g). During filling, vesical pressure increased and flow decreased, but not necessarily in-parallel. Perfusate flow decreased transiently during isovolumetric contraction, and flow increased during emptying. A reduction in perfusion pressure from ∼105 to ∼40 mmHg reduced flow from ∼70 to ∼20 mL/min-100g, and reduced flow correlated with reduced vesical pressure. Perfusate flow is dependent on bladder perfusion pressure, and not necessarily reciprocally dependent on vesical pressure. Vesical pressure is highly sensitive to the level of perfusate flow, which supports the hypothesis that vesical pressure is dependent on the level of detrusor smooth muscle contractile activity (tone), and that compliance is dependent on bladder perfusion.

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Slowly cycling rho kinase-dependent actomyosin crossbridge "slippage" explains intrinsic high compliance of detrusor smooth muscle

2017-03-29

Biological soft tissues are viscoelastic because they display time-independent pseudo-elasticity and time-dependent viscosity. Upon an imposed ramp increase then decrease in strain, the resultant stress changes, termed loading and unloading respectively, produce nonlinear stress-strain curves and a reversible reduction in the stress-strain work area that identifies viscosity. However, there is evidence that bladder may also display plasticity; an increase in strain that is unrecoverable unless work is done by the muscle. In the present study, an electronic lever was used to induce controlled changes in stress and strain to determine whether rabbit detrusor smooth muscle (rDSM) is best described as viscoelastic or viscoelastic-plastic. Using sequential ramp loading and unloading cycles, stress-strain and stiffness-stress analyses revealed that rDSM displayed reversible viscoelasticity, and that the viscous component was responsible for establishing a high stiffness at low stresses that increased only modestly with increasing stress compared to the large increase produced when the viscosity was absent and only pseudo-elasticity governed tissue behavior. The study also revealed that rDSM underwent softening correlating with plastic deformation and creep that was reversed slowly when tissues were incubated in a Ca2+-containing solution. Together, the data support a model of DSM as a viscoelastic-plastic material, and plasticity is by motor protein activation. This model explains the mechanism of intrinsic bladder compliance as "slipping" crossbridges, predicts that wall tension is dependent not only on vesicle pressure and radius but also on actomyosin crossbridge activity, and identifies a novel molecular target for compliance regulation both physiologically and therapeutically.

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Modeling the influence of acute changes in bladder elasticity on pressure and wall tension during filling

2017-02-20

Tension-sensitive nerves in the bladder wall are responsible for providing bladder sensation. Bladder wall tension, and therefore nerve output, is a function of bladder pressure, volume, geometry and material properties. The elastic modulus of the bladder is acutely adjustable, and this material property is responsible for adjustable preload tension exhibited in human and rabbit detrusor muscle strips and dynamic elasticity revealed during comparative-fill urodynamics in humans. A finite deformation model of the bladder was previously used to predict filling pressure and wall tension using uniaxial tension test data and the results showed that wall tension can increase significantly during filling with relatively little pressure change. In the present study, published uniaxial rabbit detrusor data were used to quantify regulated changes in the elastic modulus, and the finite deformation model was expanded to illustrate the potential effects of elasticity changes on pressure and wall tension during filling. The model demonstrates a shift between relatively flat pressure-volume filling curves, which is consistent with a recent human urodynamics study, and also predicts that dynamic elasticity would produce significant changes in wall tension during filling. The model results support the conclusion that acute regulation of bladder elasticity could contribute to significant changes in wall tension for a given volume that could lead to urgency, and that a single urodynamic fill may be insufficient to characterize bladder biomechanics. The model illustrates the potential value of quantifying wall tension in addition to pressure during urodynamics.

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Low amplitude rhythmic contraction frequency in human detrusor strips correlates with phasic intravesical pressure waves

2016-12-26

Low amplitude rhythmic contractions (LARC) occur in detrusor smooth muscle and may play a role in storage disorders such as overactive bladder and detrusor overactivity. The purpose of this study was to determine whether LARC frequencies identified in vitro from strips of human urinary bladder tissue correlate with in vivo LARC frequencies, visualized as phasic intravesical pressure (pves) waves during urodynamics (UD).

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Non‐invasive characterization of real‐time bladder sensation using accelerated hydration and a novel sensation meter: An initial experience

2016-09-21

The purpose of this investigation was to develop a non-invasive, objective, and unprompted method to characterize real-time bladder sensation.

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A pilot study to measure dynamic elasticity of the bladder during urodynamics

2016-05-31

Previous studies using isolated strips of human detrusor muscle identified adjustable preload tension, a novel mechanism that acutely regulates detrusor wall tension. The purpose of this investigation was to develop a method to identify a correlate measure of adjustable preload tension during urodynamics.

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Acute length adaptation and adjustable preload in the human detrusor

2015-07-30

The biomechanical properties of length adaptation and adjustable preload have been previously identified in detrusor smooth muscle in animal models. This in vitro study aims to show that human detrusor smooth muscle exhibits length adaptation and adjustable preload tension which could play an important role in both overactive bladder and detrusor underactivity.

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The Cath-Assist: A Self-Catheterization Assistive Device

2015-06-01

The Cath-Assist: A Self-Catheterization Assistive Device

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A new and automated method for objective analysis of detrusor rhythm during the filling phase

2014-02-28

There is growing acceptance that the detrusor muscle is not silent during the filling phase of the micturition cycle but displays low-amplitude phasic contractions that have been associated with urinary urgency. Unfortunately, there is currently no standardized methodology to quantify detrusor rhythm during the filling phase. Therefore, the purpose of this study was to develop an automated computer algorithm to analyze rat detrusor rhythm in a quick, accurate, and reproducible manner.

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Fourier Transform Analysis of Rabbit Detrusor Autonomous Contractions Reveals Length Dependent Increases in Tone and Slow Wave Development at Long Lengths

2013-07-31

Bladder wall muscle (detrusor) develops low amplitude rhythmic contractions. Low amplitude rhythmic contraction activity is increased in detrusor from patients with overactive bladder. In this in vitro study we used fast Fourier transforms to assess the length dependence of low amplitude rhythmic contraction components.

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Carbachol-Induced Volume Adaptation in Mouse Bladder and Length Adaptation via Rhythmic Contraction in Rabbit Detrusor

2012-10-31

The length–tension (L–T) relationships in rabbit detrusor smooth muscle (DSM) are similar to those in vascular and airway smooth muscles and exhibit short-term length adaptation characterized by L–T curves that shift along the length axis as a function of activation and strain history. In contrast to skeletal muscle, the length–active tension (L–Ta) curve for rabbit DSM strips does not have a unique peak tension value with a single ascending and descending limb. Instead, DSM can exhibit multiple ascending and descending limbs, and repeated KCl-induced contractions at a particular muscle length on an ascending or descending limb display increasingly greater tension. In the present study, mouse bladder strips with and without urothelium exhibited KCl-induced and carbachol-induced length adaptation, and the pressure–volume relationship in mouse whole bladder displayed short-term volume adaptation. Finally, prostaglandin-E2-induced low-level rhythmic contraction produced length adaptation in rabbit DSM strips. A likely role of length adaptation during bladder filling is to prepare DSM cells to contract efficiently over a broad range of volumes. Mammalian bladders exhibit spontaneous rhythmic contraction (SRC) during the filling phase and SRC is elevated in humans with overactive bladder (OAB). The present data identify a potential physiological role for SRC in bladder adaptation and motivate the investigation of a potential link between short-term volume adaptation and OAB with impaired contractility.

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Adjustable passive stiffness in mouse bladder: regulated by Rho kinase and elevated following partial bladder outlet obstruction

2012-04-15

Detrusor smooth muscle (DSM) contributes to bladder wall tension during filling, and bladder wall deformation affects the signaling system that leads to urgency. The length-passive tension (L-Tp) relationship in rabbit DSM can adapt with length changes over time and exhibits adjustable passive stiffness (APS) characterized by a L-Tp curve that is a function of both activation and strain history. Muscle activation with KCl, carbachol (CCh), or prostaglandin E2 at short muscle lengths can increase APS that is revealed by elevated pseudo-steady-state Tp at longer lengths compared with prior Tp measurements at those lengths, and APS generation is inhibited by the Rho Kinase (ROCK) inhibitor H-1152. In the current study, mouse bladder strips exhibited both KCl- and CCh-induced APS. Whole mouse bladders demonstrated APS which was measured as an increase in pressure during passive filling in calcium-free solution following CCh precontraction compared with pressure during filling without precontraction. In addition, CCh-induced APS in whole mouse bladder was inhibited by H-1152, indicating that ROCK activity may regulate bladder compliance during filling. Furthermore, APS in whole mouse bladder was elevated 2 wk after partial bladder outlet obstruction, suggesting that APS may be relevant in diseases affecting bladder mechanics. The presence of APS in mouse bladder will permit future studies of APS regulatory pathways and potential alterations of APS in disease models using knockout transgenetic mice.

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Elevated steady-state bladder preload activates myosin phosphorylation: detrusor smooth muscle is a preload tension sensor

2012-12-01

In rabbit bladder wall (detrusor) muscle, the degree of tone induced during physiological filling (filling tone) is the sum of adjustable preload tension and autonomous contractile tension. The present study was designed to determine whether the level of filling tone is dependent on detrusor muscle length. Maximum active tension induced by KCl was parabolic in relation to length [tension increased from 70% to 100% of a reference length (Lref) and decreased at longer muscle lengths]. Filling tone, however, increased in a linear fashion from 70% to 120% Lref. In the presence of ibuprofen to abolish autonomous contraction and retain adjustable preload tension, tension was reduced in strength but remained linearly dependent on length from 70% to 120% Lref. In the absence of autonomous contraction, stretching detrusor muscle from 80% to 120% Lref still caused an increase in tone during PGE2-induced rhythmic contraction, suggesting that muscle stretch caused increases in detrusor muscle contractile sensitivity rather than in prostaglandin release. In the absence of autonomous contraction, the degree of adjustable preload tension and myosin phosphorylation increased when detrusor was stretched from 80% to 120% Lref, but also displayed length-hysteresis, indicating that detrusor muscle senses preload rather than muscle length. Together, these data support the hypothesis that detrusor muscle acts as a preload tension sensor. Because detrusor muscle is in-series with neuronal mechanosensors responsible for urinary urgency, a more thorough understanding of detrusor muscle filling tone may reveal unique targets for therapeutic intervention of contractile disorders such as overactive bladder.

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Active tension adaptation at a shortened arterial muscle length: inhibition by cytochalasin-D

2011-04-01

Unlike the static length-tension curve of striated muscle, airway and urinary bladder smooth muscles display a dynamic length-tension curve. Much less is known about the plasticity of the length-tension curve of vascular smooth muscle. The present study demonstrates that there were significant increases of ∼15% in the phasic phase and ∼10% in the tonic phase of a third KCl-induced contraction of a rabbit femoral artery ring relative to the first contraction after a 20% decrease in length from an optimal muscle length (L0) to 0.8-fold L0. Typically, three repeated contractions were necessary for full length adaptation to occur. The tonic phase of a third KCl-induced contraction was increased by ∼50% after the release of tissues from 1.25-fold to 0.75-fold Lo. The mechanism for this phenomenon did not appear to lie in thick filament regulation because there was no increase in myosin light chain (MLC) phosphorylation to support the increase in tension nor was length adaptation abolished when Ca2+ entry was limited by nifedipine and when Rho kinase (ROCK) was blocked by H-1152. However, length adaptation of both the phasic and tonic phases was abolished when actin polymerization was inhibited through blockade of the plus end of actin by cytochalasin-D. Interestingly, inhibition of actin polymerization when G-actin monomers were sequestered by latrunculin-B increased the phasic phase and had no effect on the tonic phase of contraction during length adaptation. These data suggest that for a given level of cytosolic free Ca2+, active tension in the femoral artery can be sensitized not only by regulation of MLC phosphatase via ROCK and protein kinase C, as has been reported by others, but also by a nonmyosin regulatory mechanism involving actin polymerization. Dysregulation of this form of active tension modulation may provide insight into alterations of large artery stiffness in hypertension.

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Length Adaptation of the Passive-to-Active Tension Ratio in Rabbit Detrusor

2010-08-31

The passive and active length–tension (L–Tp and L–Ta) relationships in airway, vascular, and detrusor smooth muscles can adapt with length changes and/or multiple contractions. The present objectives were to (1) determine whether short-term adaptation at one muscle length shifts the entire L–Ta curve in detrusor smooth muscle (DSM), (2) compare adaptation at shorter versus longer lengths, and (3) determine the effect of adaptation on the Tp/Ta ratio. Results showed that multiple KCl-induced contractions on the descending limb of the original L–Ta curve adapted DSM strips to that length and shifted the L–Ta curve rightward. Peak Ta at the new length was not different from the original peak Ta, and the L–Tp curve shifted rightward with the L–Ta curve. Multiple contractions on the ascending limb increased both Ta and Tp. In contrast, multiple contractions on the descending limb increased Ta but decreased Tp. The Tp/Ta ratio on the original descending limb adapted from 0.540 ± 0.084 to 0.223 ± 0.033 (mean ± SE, n = 7), such that it was not different from the ratio of 0.208 ± 0.033 at the original peak Ta length, suggesting a role of length adaptation may be to maintain a desirable Tp/Ta ratio as the bladder fills and voids over a broad DSM length range.

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Evidence that actomyosin cross bridges contribute to “passive” tension in detrusor smooth muscle

2010-06-01

Contraction of detrusor smooth muscle (DSM) at short muscle lengths generates a stiffness component we termed adjustable passive stiffness (APS) that is retained in tissues incubated in a Ca2+-free solution, shifts the DSM length-passive tension curve up and to the left, and is softened by muscle strain and release (strain softened). In the present study, we tested the hypothesis that APS is due to slowly cycling actomyosin cross bridges. APS and active tension produced by the stimulus, KCl, displayed similar length dependencies with identical optimum length values. The myosin II inhibitor blebbistatin relaxed active tension maintained during a KCl-induced contraction and the passive tension maintained during stress-relaxation induced by muscle stretch in a Ca2+-free solution. Passive tension was attributed to tension maintaining rather than tension developing cross bridges because tension did not recover after a rapid 10% stretch and release as it did during a KCl-induced contraction. APS generated by a KCl-induced contraction in intact tissues was preserved in tissues permeabilized with Triton X-100. Blebbistatin and the actin polymerization inhibitor latrunculin-B reduced the degree of APS generated by a KCl-induced contraction. The degree of APS generated by KCl was inhibited to a greater degree than was the peak KCl-induced tension by rhoA kinase and cyclooxygenase inhibitors. These data support the hypothesis that APS is due to slowly cycling actomyosin cross bridges and suggest that cross bridges may play a novel role in DSM that uniquely serves to ensure proper contractile function over an extreme working length range.

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Rhythmic contraction generates adjustable passive stiffness in rabbit detrusor

2010-03-01

The length-tension (L-T) relationships in airway and vascular smooth muscles have been shown to adapt with length changes over time. Our prior studies have shown that the active and passive L-T relationships in rabbit detrusor smooth muscle (DSM) can adapt and that DSM exhibits adjustable passive stiffness (APS) characterized by a passive L-T curve that is a function of strain and activation history. The present study demonstrates that passive tension due to APS can represent a substantial fraction of total tension over a broad length range. Our previous studies have shown that maximal KCl-induced contractions at short muscle lengths generate APS that is revealed by increased pseudo-steady-state passive tension at longer lengths compared with previous measurements at those lengths. The objective of the present study was to determine the mechanisms involved in APS generation. Increasing the number of KCl-induced contractions or the duration of a contraction increased the amount of APS generated. Furthermore, a fraction of APS was restored in calcium-free solution and was sensitive to the general serine and threonine protein kinase inhibitor staurosporine. Most importantly, rhythmic contraction (RC) generated APS, and because RC occurs spontaneously in human bladder, a physiological role for RC was potentially identified.

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Adaptation of the length-active tension relationship in rabbit detrusor

2009-10-01

Studies have shown that the length-tension (L-T) relationships in airway and vascular smooth muscles are dynamic and can adapt to length changes over a period of time. Our prior studies have shown that the passive L-T relationship in rabbit detrusor smooth muscle (DSM) is also dynamic and that DSM exhibits adjustable passive stiffness (APS) characterized by a passive L-T curve that can shift along the length axis as a function of strain history and activation history. The present study demonstrates that the active L-T curve for DSM is also dynamic and that the peak active tension produced at a particular muscle length is a function of both strain and activation history. More specifically, this study reveals that the active L-T relationship, or curve, does not have a unique peak tension value with a single ascending and descending limb, but instead reveals that multiple ascending and descending limbs can be exhibited in the same DSM strip. This study also demonstrates that for DSM strips not stretched far enough to reveal a descending limb, the peak active tension produced by a maximal KCl-induced contraction at a short, passively slack muscle length of 3 mm was reduced by 58.6 ± 4.1% (n = 15) following stretches to and contractions at threefold the original muscle length, 9 mm. Moreover, five subsequent contractions at the short muscle length displayed increasingly greater tension; active tension produced by the sixth contraction was 91.5 ± 9.1% of that produced by the prestretch contraction at that length. Together, these findings indicate for the first time that DSM exhibits length adaptation, similar to vascular and airway smooth muscles. In addition, our findings demonstrate that preconditioning, APS and adaptation of the active L-T curve can each impact the maximum total tension observed at a particular DSM length.

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Stimulated calcium entry and constitutive RhoA kinase activity cause stretch-induced detrusor contraction

2008 Urinary bladder wall muscle (i.e., detrusor smooth muscle; DSM) contracts in response to a quick-stretch, but this response is neither fully characterized, nor completely understood at the subcellular level. Strips of rabbit DSM were quick-stretched (5 ms) and held isometric for 10 s to measure the resulting peak quick-stretch contractile response (PQSR). The ability of selective Ca(2+) channel blockers and kinase inhibitors to alter the PQSR was measured, and the phosphorylation levels of myosin light chain (MLC) and myosin phosphatase targeting regulatory subunit (MYPT1) were recorded. DSM responded to a quick-stretch with a biphasic response consisting of an initial contraction peaking at 0.24+/-0.02-fold the maximum KCl-induced contraction (F(o)) by 1.48+/-0.17 s (PQSR) before falling to a weaker tonic (10 s) level (0.12+/-0.03-fold F(o)). The PQSR was dependent on the rate and degree of muscle stretch, displayed a refractory period, and was converted to a sustained response in the presence of muscarinic receptor stimulation. The PQSR was inhibited by nifedipine, 2-aminoethoxydiphenyl borate (2-APB), 100 microM gadolinium and Y-27632, but not by atropine, 10 microM gadolinium, LOE-908, cyclopiazonic acid, or GF-109203X. Y-27632 and nifedipine abolished the increase in MLC phosphorylation induced by a quick-stretch. Y-27632, but not nifedipine, inhibited basal MYPT1 phosphorylation, and a quick-stretch failed to increase phosphorylation of this rhoA kinase (ROCK) substrate above the basal level. These data support the hypothesis that constitutive ROCK activity is required for a quick-stretch to activate Ca(2+) entry and cause a myogenic contraction of DSM.

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Low-cost IR reflective sensors for submicrolevel position measurement and control

2008 This paper investigates the feasibility of using commercially available, low-cost IR reflective sensors for micro- to submicroscale position measurement and control. These sensors are typically used as optical switches; however, their application for detecting fine motion, such as the movement of a piezoactuator, has not been investigated. Five IR sensors were evaluated to determine their range, resolution, linear distortion, noise characteristics, and bandwidth. Experimental results show that the performance of the IR sensors compares well with a commercial inductive sensor that costs significantly more. For example, the measured resolution was within several hundred nanometers over a ±200 μm range and the linear distortion was significantly lower than the inductive sensor. A selected IR sensor was used in the design of a state-feedback control system to compensate for hysteresis and creep in an experimental piezopositioner. Compared to the open-loop system, by using the IR sensor in feedback, the output hysteresis was reduced by over 95%. These results show the potential of such sensors in the design of low-cost microprecision mechatronic positioning systems.

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Adjustable passive length-tension curve in rabbit detrusor smooth muscle

2007-05-01

Until the 1990s, the passive and active length-tension (L-T) relationships of smooth muscle were believed to be static, with a single passive force value and a single maximum active force value for each muscle length. However, recent studies have demonstrated that the active L-T relationship in airway smooth muscle is dynamic and adapts to length changes over a period of time. Furthermore, our prior work showed that the passive L-T relationship in rabbit detrusor smooth muscle (DSM) is also dynamic and that in addition to viscoelastic behavior, DSM displays strain-softening behavior characterized by a loss of passive stiffness at shorter lengths following a stretch to a new longer length. This loss of passive stiffness appears to be irreversible when the muscle is not producing active force and during submaximal activation but is reversible on full muscle activation, which indicates that the stiffness component of passive force lost to strain softening is adjustable in DSM. The present study demonstrates that the passive L-T curve for DSM is not static and can shift along the length axis as a function of strain history and activation history. This study also demonstrates that adjustable passive stiffness (APS) can modulate total force (35% increase) for a given muscle length, while active force remains relatively unchanged (4% increase). This finding suggests that the structures responsible for APS act in parallel with the contractile apparatus, and the results are used to further justify the configuration of modeling elements within our previously proposed mechanical model for APS.

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A mechanical model for adjustable passive stiffness in rabbit detrusor

2006-10-01

Strips of rabbit detrusor smooth muscle (DSM) exhibit adjustable passive stiffness characterized by strain softening: a loss of stiffness on stretch to a new length distinct from viscoelastic behavior. At the molecular level, strain softening appears to be caused by cross-link breakage and is essentially irreversible when DSM is maintained under passive conditions (i.e., when cross bridges are not cycling to produce active force). However, on DSM activation, strain softening is reversible and likely due to cross-link reformation. Thus DSM displays adjustable passive stiffness that is dependent on the history of both muscle strain and activation. The present study provides empirical data showing that, in DSM, 1) passive isometric force relaxation includes a very slow component requiring hours to approach steady state, 2) the level of passive force maintained at steady state is less if the tissue has previously been strain softened, and 3) tissues subjected to a quick-release protocol exhibit a biphasic response consisting of passive force redevelopment followed by force relaxation. To explain these and previously identified characteristics, a mechanical model for adjustable passive stiffness is proposed based on the addition of a novel cross-linking element to a hybrid Kelvin/Voigt viscoelastic model.

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Resistance to pressure-induced dilatation in femoral but not saphenous artery: physiological role of latch?

2006-10-01

We recently determined that the ability of the femoral artery (FA) to maintain higher levels of tonic isometric stress compared with the saphenous artery (SA) was due to differential expression of motor proteins permitting latch-bridge formation in FA and not SA. Arteries under pressure in vivo are not constrained to contract isometrically. Thus the significance of latch-bridge formation in arterial physiology remains to be determined. To address this translational question, diameter changes of pressurized FA and SA were compared. The reduction in lumen diameter induced by KCl at 80 mmHg (isobaric active constriction; IAC) was greater at 30 s than 10 min in SA. In FA, the reverse was true, mimicking isometric contractile responses identified in our earlier work. From 80 to 150 mmHg, the %IAC induced by KCl was greater in SA than FA (e.g., ∼80% vs. ∼30% at 120 mmHg). This was not explained by differences in contractile mechanisms but was likely due to differences in absolute artery diameters. In constricted arteries subjected to a ramp increase in pressure from 60 to 120 mmHg, the constricted diameter of FA, but not SA, was greater than the IAC diameter at each pressure. Thus FA but not SA could maintain a smaller diameter on being pressurized when first constricted than it could achieve by isobaric constriction. These data support the hypothesis that latch bridges permit constricted large-diameter elastic arteries such as the FA to temporarily resist dilatation in the face of transient increases in blood pressures.

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Evidence for absence of latch-bridge formation in muscular saphenous arteries

2006-07-01

Large-diameter elastic arteries can produce strong contractions indefinitely at a high-energy economy by the formation of latch bridges. Whether downstream blood vessels also use latch bridges remains unknown. The zero-pressure medial thickness and lumen diameter of rabbit saphenous artery (SA), a muscular branch of the elastic femoral artery (FA), were, respectively, approximately twofold and half-fold that of the FA. In isolated FA and SA rings, KCl rapidly (

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ROK-induced cross-link formation stiffens passive muscle: reversible strain-induced stress softening in rabbit detrusor

2005-07-01

Passive mechanical properties of strips of rabbit detrusor smooth muscle were examined and found by cyclic loading in a calcium-free solution to display viscoelastic softening and strain-induced stress softening (strain softening). Strain softening, or the Mullins effect, is a loss of stiffness attributed to the breakage of cross-links, and appeared irreversible in detrusor even after the return of spontaneous rhythmic tone during 120 min of incubation in a calcium-containing solution. However, 3 min of KCl or carbachol (CCh)-induced contraction permitted rapid regeneration of the passive stiffness lost to strain softening, and 3 μM of the RhoA kinase (ROK) inhibitor Y-27632 prevented this regeneration. The degree of ROK-induced passive stiffness was inversely dependent on muscle length over a length range where peak CCh-induced force was length independent. Thus rabbit detrusor displayed variable passive stiffness both strain- and activation-history dependent. In conclusion, activation of ROK by KCl or CCh increased passive stiffness softened by muscle strain and thereby attributed to cross-links that remained stable during tissue incubation in a calcium-free solution. Degradation of this signaling system could potentially contribute to urinary incontinence.

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Modeling the human hand as it interacts with a telemanipulation system

2005-11-01

This paper describes the development of a linear lumped-parameter hand/arm model for the operator of a telemanipulation system. The authors previously developed a control architecture that implements frequency-domain loop-shaping compensators to improve the transparency or “feel” of a telemanipulation system, and a human model is used when simulating this architecture. Typically, the human is modeled as a second order mass–spring–damper system. The five-parameter model presented in this paper, however, includes an additional spring and damper to better approximate the dynamics within the specific frequency range for which compensators will be designed, typically below 20–30 Hz. The model form and parameters were determined from experimental data taken from a telemanipulation system with a single translational degree-of-freedom. Additional data was taken from a system with three actuated degrees-of-freedom, and a set of model parameters was determined for each direction of motion. Each set of model parameters presented in this paper is for the specific grip type and hand/arm orientation used during interaction with each particular telemanipulation system, however similar sets of parameters using this human model could be obtained for interaction with other telemanipulation systems and haptic interfaces. A comparison of the five-parameter model with a two-parameter spring–damper model suggests that in some cases the use of additional model parameters may not offer a significant improvement.

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An implementation of loop-shaping compensation for multidegree-of-freedom macro-microscaled telemanipulation

2005-05-01

This brief describes the implementation of a telemanipulation control architecture on a three degree-of-freedom (3-DOF) scaled master-slave telemanipulation system. Specifically, feedback linearization enables the use of loop-shaping compensators to increase the transparency bandwidth of a 3-DOF macro-micro telemanipulator pair, while the stability robustness of the system is maintained. Experimental results contrast the transparency and stability robustness of the compensated with the uncompensated system. The enhanced performance of the former demonstrates the utility of the approach.

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A compliant-mechanism-based three degree-of-freedom manipulator for small-scale manipulation

2000-01-01

This paper describes the design of a small-scale three degree-of-freedom compliant-mechanism-based manipulator with an approximately 2 cm×2 cm×2 cm cubic workspace. The manipulator exhibits a significantly larger range of motion and better spatial structural properties than a conventional compliant mechanism, due primarily to a unique flexure joint developed by the authors. A brief description of the mechanics of the flexure joint is followed by a description of the design of the manipulator. Following the mechanical description, the design of the low-level manipulator controller is discussed. Finally, data is presented that demonstrates manipulator performance.

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A Well-Behaved Revolute Flexure Joint for Compliant Mechanism Design

1999-09-01

This paper describes the design of a unique revolute flexure joint, called a split-tube flexure, that enables (lumped compliance) compliant mechanism design with a considerably larger range-of-motion than a conventional thin beam flexure, and additionally provides significantly better multi-axis revolute joint characteristics. Conventional flexure joints utilize bending as the primary mechanism of deformation. In contrast, the split-tube flexure joint incorporates torsion as the primary mode of deformation, and contrasts the torsional properties of a thin-walled open-section member with the bending properties of that member to obtain desirable joint behavior. The development of this joint enables the development of compliant mechanisms that are quite compliant along kinematic axes, extremely stiff along structural axes, and are capable of kinematically well-behaved large motions.

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