Effect of supraspinatus tendon injury on supraspinatus and infraspinatus muscle passive tension and associated biochemistry.

BACKGROUND: Injury to the supraspinatus and infraspinatus tendons and the associated atrophic changes to the muscle remain a common clinical problem. Specifically, increased muscle stiffness has been implicated in failure of the repair and poor functional outcomes. We present a comparison of the passive mechanical properties and associated biochemical studies from patients with and without torn supraspinatus tendons. METHODS: Muscle biopsy samples (n = 40) were obtained from twenty patients undergoing arthroscopic shoulder surgery. Passive mechanical tests of both individual fibers and fiber bundles as well as analysis of titin molecular weight and collagen content were performed. RESULTS: At the fiber-bundle level, a significant increase in passive modulus was observed between intact supraspinatus samples (mean [and standard error], 237.41 ± 59.78 kPa) and torn supraspinatus samples (515.74 ± 65.48 kPa) (p < 0.05), a finding that was not observed at the single fiber level. Within the torn samples, elastic moduli in the supraspinatus were greater than in the infraspinatus at both the single fiber and the fiber-bundle level. There was a significant positive correlation between bundle elastic modulus and collagen content (r(2) = 0.465) in the supraspinatus muscle as well as a significant positive correlation between tear size and bundle elastic modulus (r(2) = 0.702) in the torn supraspinatus samples. CONCLUSIONS: Supraspinatus muscle passive tension increases in a tendon tear size-dependent manner after tendon injury. The increase in muscle stiffness appears to originate outside the muscle cell, in the extracellular matrix. CLINICAL RELEVANCE: Muscle stiffness after rotator cuff tendon injury is more severe with large tears. This finding supports the concept of early intervention, when tendon tears are smaller, and interventions targeting the extracellular matrix.

Glutamate receptors in the nucleus tractus solitarius contribute to ventilatory acclimatization to hypoxia in rat.

When exposed to a hypoxic environment the body's first response is a reflex increase in ventilation, termed the hypoxic ventilatory response (HVR). With chronic sustained hypoxia (CSH), such as during acclimatization to high altitude, an additional time-dependent increase in ventilation occurs, which increases the HVR. This secondary increase persists after exposure to CSH and involves plasticity within the circuits in the central nervous system that control breathing. Currently these mechanisms of HVR plasticity are unknown and we hypothesized that they involve glutamatergic synapses in the nucleus tractus solitarius (NTS), where afferent endings from arterial chemoreceptors terminate. To test this, we treated rats held in normoxia (CON) or 10% O2 (CSH) for 7 days and measured ventilation in conscious, unrestrained animals before and after microinjecting glutamate receptor agonists and antagonists into the NTS. In normoxia, AMPA increased ventilation 25% and 50% in CON and CSH, respectively, while NMDA doubled ventilation in both groups (P < 0.05). Specific AMPA and NMDA receptor antagonists (NBQX and MK801, respectively) abolished these effects. MK801 significantly decreased the HVR in CON rats, and completely blocked the acute HVR in CSH rats but had no effect on ventilation in normoxia. NBQX decreased ventilation whenever it was increased relative to normoxic controls; i.e. acute hypoxia in CON and CSH, and normoxia in CSH. These results support our hypothesis that glutamate receptors in the NTS contribute to plasticity in the HVR with CSH. The mechanism underlying this synaptic plasticity is probably glutamate receptor modification, as in CSH rats the expression of phosphorylated NR1 and GluR1 proteins in the NTS increased 35% and 70%, respectively, relative to that in CON rats.

Human skeletal muscle biochemical diversity.

The molecular components largely responsible for muscle attributes such as passive tension development (titin and collagen), active tension development (myosin heavy chain, MHC) and mechanosensitive signaling (titin) have been well studied in animals but less is known about their roles in humans. The purpose of this study was to perform a comprehensive analysis of titin, collagen and MHC isoform distributions in a large number of human muscles, to search for common themes and trends in the muscular organization of the human body. In this study, 599 biopsies were obtained from six human cadaveric donors (mean age 83 years). Three assays were performed on each biopsy - titin molecular mass determination, hydroxyproline content (a surrogate for collagen content) and MHC isoform distribution. Titin molecular mass was increased in more distal muscles of the upper and lower limbs. This trend was also observed for collagen. Percentage MHC-1 data followed a pattern similar to collagen in muscles of the upper extremity but this trend was reversed in the lower extremity. Titin molecular mass was the best predictor of anatomical region and muscle functional group. On average, human muscles had more slow myosin than other mammals. Also, larger titins were generally associated with faster muscles. These trends suggest that distal muscles should have higher passive tension than proximal ones, and that titin size variability may potentially act to 'tune' the protein's mechanotransduction capability.

ISSLS prize winner: Adaptations to the multifidus muscle in response to experimentally induced intervertebral disc degeneration.

STUDY DESIGN: Basic science study of the rabbit multifidus muscle response to intervertebral disc degeneration. OBJECTIVE: To assess changes in passive mechanical properties, associated protein structure, and histology of multifidus in response to disc degeneration produced by experimental needle puncture. SUMMARY OF BACKGROUND DATA: Relationships have been reported between muscle dysfunction and low back injury; however, little is known about the cause and effect of such relationships. METHODS: Twelve rabbits were studied; 4 in each of 3 groups: control, 4-weeks postintervertebral disc injury (4-week disc degeneration), and 12-weeks postintervertebral disc injury (12-week disc degeneration). Single multifidus fibers and bundles of fibers were isolated and tested for slack sarcomere length and elastic modulus. Titin isoform mass, myosin heavy chain distribution, and muscle histology were also examined. RESULTS: Compared to control, individual muscle fibers were 34% stiffer and fiber bundles 107% stiffer in the 12-week disc degeneration group. No changes were detected at 4-week disc degeneration. No statistically significant change was found for MHC distribution in the 12-week disc degeneration group when compared to control, whereas titin isoforms were larger (P < 0.05) in the 12-week disc degeneration group. Histology revealed select regions of multifidus, at 12-week disc degeneration, with increased space between bundles of fibers, which in some instances was partly occupied by adipose tissue. CONCLUSION: Multifidus becomes stiffer, both in individual fibers and fiber bundles, in response to experimentally induced intervertebral disc degeneration. This cannot be explained by change in fiber-type due to reduced muscle use, nor by the increased size of the protein titin (which would reduce stiffness). We hypothesize that fiber bundles become stiffer by proliferation and/or reorganization of collagen content within the muscle but the basis for fiber stiffening is not known.

Pulmonary artery pressure responses to increased cardiac output in chickens with raised metabolic rate.

Previous work has shown remarkable differences in the pressure-flow relations of the pulmonary circulation between birds and mammals. For example several studies suggest that the avian pulmonary blood vessels behave like rigid tubes, very different from the situation in mammalian lung. We therefore speculated that birds would develop high pulmonary artery pressures when the cardiac output was substantially increased during heavy exercise, for example during flight. However because of the technical difficulties of measuring pulmonary artery pressures in flight, the metabolic rate and cardiac output in anesthetized chickens were increased by infusing 2,4 Dinitrophenol (DNP) and the mean pressure was measured by means of a catheter in the pulmonary artery. Although the pulmonary artery pressure rose steadily as cardiac output increased, it remained below the high levels predicted from the previous studies for similar changes in pulmonary blood flow. Furthermore the increase in pressure was less than in mammals where recruitment and distension of pulmonary capillaries are known to occur. The reasons for this unexpected result are not clear.