Optical coherence tomography-based contact indentation for diaphragm mechanics in a mouse model of transforming growth factor alpha induced lung disease

Funding provided by the National Health and Medical Research Council (NHMRC) of Australia (1027218). P.N. and K.W. are supported by NHMRC Fellowships (1045824, 1090888). P.W. was supported by the William and Marlene Schrader Postgraduate Scholarship, The University of Western Australia, and C.A. by an NHMRC Preterm Infants CRE top-up scholarship.This study tested the utility of optical coherence tomography (OCT)-based indentation to assess mechanical properties of respiratory tissues in disease. Using OCT-based indentation, the elastic modulus of mouse diaphragm was measured from changes in diaphragm thickness in response to an applied force provided by an indenter. We used a transgenic mouse model of chronic lung disease induced by the overexpression of transforming growth factor-alpha (TGF-α), established by the presence of pleural and peribronchial fibrosis and impaired lung mechanics determined by the forced oscillation technique and plethysmography. Diaphragm elastic modulus assessed by OCT-based indentation was reduced by TGF-α at both left and right lateral locations (p < 0.05). Diaphragm elastic modulus at left and right lateral locations were correlated within mice (r = 0.67, p < 0.01) suggesting that measurements were representative of tissue beyond the indenter field. Co-localised images of diaphragm after TGF-α overexpression revealed a layered fibrotic appearance. Maximum diaphragm force in conventional organ bath studies was also reduced by TGF-α overexpression (p < 0.01). Results show that OCT-based indentation provided clear delineation of diseased diaphragm, and together with organ bath assessment, provides new evidence suggesting that TGF-α overexpression produces impairment in diaphragm function and, therefore, an increase in the work of breathing in chronic lung disease.Publisher PDFPeer reviewe

Age- and Gender-Related Changes in Contractile Properties of Non-Atrophied EDL Muscle

Background: In humans, ageing causes skeletal muscles to become atrophied, weak, and easily fatigued. In rodent studies, ageing has been associated with significant muscle atrophy and changes in the contractile properties of the muscles. However, it is not entirely clear whether these changes in contractile properties can occur before there is significant atrophy, and whether males and females are affected differently. Methods and Results: We investigated various contractile properties of whole isolated fast-twitch EDL muscles from adult (2–6 months-old) and aged (12–22 months-old) male and female mice. Atrophy was not present in the aged mice. Compared with adult mice, EDL muscles of aged mice had significantly lower specific force, longer tetanus relaxation times, and lower fatiguability. In the properties of absolute force and muscle relaxation times, females were affected by ageing to a greater extent than males. Additionally, EDL muscles from a separate group of male mice were subjected to eccentric contractions of 15 % strain, and larger force deficits were found in aged than in adult mice. Conclusion: Our findings provide further insight into the muscle atrophy, weakness and fatiguability experienced by the elderly. We have shown that even in the absence of muscle atrophy, there are definite alterations in the physiological properties of whole fast-twitch muscle from ageing mice, and for some of these properties the alterations are mor

Similarities and Differences of the Soleus and Gastrocnemius H-reflexes during Varied Body Postures, Foot Positions, and Muscle Function: Multifactor Designs for Repeated Measures

<p>Abstract</p> <p>Background</p> <p>Although the soleus (Sol), medial gastrocnemius (MG), and lateral gastrocnemius (LG) muscles differ in function, composition, and innervations, it is a common practice is to investigate them as single H-reflex recording. The purpose of this study was to compare H-reflex recordings between these three sections of the triceps surae muscle group of healthy participants while lying and standing during three different ankle positions.</p> <p>Methods</p> <p>The Sol, MG and LG muscles' H-reflexes were recorded from ten participants during prone lying and standing with the ankle in neutral, maximum dorsiflexion, and maximum plantarflexion positions. Four traces were averaged for each combination of conditions. Three-way ANOVAs (posture X ankle position X muscle) with planned comparisons were used for statistical comparisons.</p> <p>Results</p> <p>Although the H-reflex in the three muscle sections differed in latency and amplitude, its dependency on posture and ankle position was similar. The H-reflex amplitudes and maximum H-reflex to M-response (H/M) ratios were significantly 1) lower during standing compared to lying with the ankle in neutral, 2) greater during standing with the ankle in plantarflexion compared to neutral, and 3) less with the ankle in dorsiflexion compared to neutral during lying and standing for all muscles (<it>p </it>≤ .05).</p> <p>Conclusion</p> <p>Varying demands are required for muscles activated during distinctly different postures and ankle movement tasks.</p

A Mathematical Model of Muscle Containing Heterogeneous Half-Sarcomeres Exhibits Residual Force Enhancement

A skeletal muscle fiber that is stimulated to contract and then stretched from L1 to L2 produces more force after the initial transient decays than if it is stimulated at L2. This behavior has been well studied experimentally, and is known as residual force enhancement. The underlying mechanism remains controversial. We hypothesized that residual force enhancement could reflect mechanical interactions between heterogeneous half-sarcomeres. To test this hypothesis, we subjected a computational model of interacting heterogeneous half-sarcomeres to the same activation and stretch protocols that produce residual force enhancement in real preparations. Following a transient period of elevated force associated with active stretching, the model predicted a slowly decaying force enhancement lasting >30 seconds after stretch. Enhancement was on the order of 13% above isometric tension at the post-stretch muscle length, which agrees well with experimental measurements. Force enhancement in the model was proportional to stretch magnitude but did not depend strongly on the velocity of stretch, also in agreement with experiments. Even small variability in the strength of half-sarcomeres (2.1% standard deviation, normally distributed) was sufficient to produce a 5% force enhancement over isometric tension. Analysis of the model suggests that heterogeneity in half-sarcomeres leads to residual force enhancement by storing strain energy introduced during active stretch in distributions of bound cross-bridges. Complex interactions between the heterogeneous half-sarcomeres then dissipate this stored energy at a rate much slower than isolated cross-bridges would cycle. Given the variations in half-sarcomere length that have been observed in real muscle preparations and the stochastic variability inherent in all biological systems, half-sarcomere heterogeneity cannot be excluded as a contributing source of residual force enhancement

The Viscoelastic Properties of Passive Eye Muscle in Primates. I: Static Forces and Step Responses

The viscoelastic properties of passive eye muscles are prime determinants of the deficits observed following eye muscle paralysis, the root cause of several types of strabismus. Our limited knowledge about such properties is hindering the ability of eye plant models to assist in formulating a patient's diagnosis and prognosis. To investigate these properties we conducted an extensive in vivo study of the mechanics of passive eye muscles in deeply anesthetized and paralyzed monkeys. We describe here the static length-tension relationship and the transient forces elicited by small step-like elongations. We found that the static force increases nonlinearly with length, as previously shown. As expected, an elongation step induces a fast rise in force, followed by a prolonged decay. The time course of the decay is however considerably more complex than previously thought, indicating the presence of several relaxation processes, with time constants ranging from 1 ms to at least 40 s. The mechanical properties of passive eye muscles are thus similar to those of many other biological passive tissues. Eye plant models, which for lack of data had to rely on (erroneous) assumptions, will have to be updated to incorporate these properties

Effect of global perspective jitter on visually induced postural sway

Abstract presented at the 25th European Conference on Visual Perception, 25-29 August 2002, Glasgow, United Kingdo

Effects of simulated viewpoint jitter on visually induced postural sway

In this study we examined the effects of simulated horizontal and vertical viewpoint jitter on the vection and postural sway induced by radial patterns of optic flow. During each trial, observers were exposed sequentially to 20 s periods of radially expanding flow, radially contracting flow, and static visual scenes. For half the trials, simulated viewpoint jitter was added to the radially expanding/contracting optic flow patterns. In experiment 1, we found that, while this jitter increased the backward postural sway induced by radial expansion, it actually decreased forward postural sway induced by radial contraction. However, in experiment 2 we found that jitter increased both the forward and backward vection induced by radially expanding and contracting flow patterns. We conclude that the processes involved in postural control are more sensitive to the sensory conflicts generated by viewpoint jitter than those involved in the perception of self-motion, and that the observed asymmetries in forward and backward sway are ecological in origin

Adrenal Failure Due to Bilateral Suprarenal Infarction Associated with Systemic Nodular Panniculitis and Endarteritis

Although involvement of the periadrenal vessels is frequent in cases of hypersensitivity angiitis or polyarteritis nodosa, it rarely results in clinical adrenal insufficiency. The present case is reported, first because infarction of the suprarenals led to this clinical state, and secondly because of the unusual and complex nature of the underlying pathological process. Case Report Mr. C. B., aged 49, was admitted to hospital on July 21, 1954, complaining of continuous abdominal pain and vomiting for two days. The patient had been under treatment since 1951 for pulmonary tuber-culosis, and was receiving streptomycin and P.A.S. at the time of his admission; there had been no recent evidence of activity of the lung lesion. He had been admitted to hospital in January, 1954, com-plaining of abdominal pain for 11 days, and was found at operation to have a perforation of the small bowel. This was sutured and an end-to-end anas-tomosis of the bowel was performed. The histological report was as follows: &quot; Chronic inflammation of the wall of the small intestine, with superadded acute inflammation and peritonitis. A regional lymph node shows chronic inflammation. No specific inflammatory features.&quot; Following this operation the patient made an un-eventful recovery, but about three months before the present admission he began to complain of vague abdominal pain in the right iliac fossa and right loin associated with occasional vomiting. Two days before admission this pain became continuous and he vomited after all food. On examination the patient showed tenderness and guarding in the right iliac fossa and hypochondrium and a continued pyrexia

The Value of Rib Biopsy in the Study of Marrow Disorders

Specimens of marrow for histological examina-tion may be obtained either by sectioning the particles present in a marrow aspirate or by surgical trephine of the sternum (Custer, 1933; Dameshek, Henstell, and Valentine, 1937; White, Baker, and Griffin, 1946). The former procedure is limited in many cases by the size of the particles withdrawn, while the latter, not infrequently, yields specimens consisting largely of bone and the marrow obtained may be distorted or too small for adequate histological study. In view of these disadvantages it was decided to use rib biopsy as an alternative method for obtaining marrow for diagnostic purposes. The evaluation of normal variations and the selection and refinemen