Effect of dimethyl sulfoxide on blood-brain barrier integrity following middle cerebral artery occlusion in the rat.

Dimethyl sulfoxide (DMSO) is widely used as a solvent for other drugs, i.e., for the protein kinase C activator phorbol 12-myristate 13-acetate (PMA) and the V1a receptor-antagonist SR49059, to reduce brain edema. We studied the effect of DMSO on blood-brain barrier (BBB) integrity following middle cerebral artery occlusion (MCAO) and the consequences on brain edema development. Male Sprague-Dawley rats were randomly assigned to sham procedure or infusion of 1% DMSO, PMA (230 microg/kg in 1% DMSO), or SR49059 (1 mg/kg in 1% DMSO) followed by MCAO (each group n = 10). After a 2-hour period of ischemia and 2 hours reperfusion, the animals were sacrificed for assessment of brain water content, sodium, and potassium concentration. BBB integrity was assessed by Evans blue extravasation. Statistical analysis was performed by ANOVA followed by a Tukey post hoc test. Low-dose DMSO treatment following MCAO significantly opened the BBB on the ischemic side (p < 0.037). PMA and SR49059 did not have any additional effect on BBB compromise compared to DMSO (p = 1.000, p < 0.957, respectively). We conclude that DMSO as a vehicle for drug administration may increase the drug concentration into the extracellular space, but since BBB permeability is increased, it may also provide an avenue for development of vasogenic edema.

Protective effect of the V1a receptor antagonist SR49059 on brain edema formation following middle cerebral artery occlusion in the rat.

There exists no pharmacological treatment for fulminating brain edema. Since evidence indicates that brain aquaporin-4 (AQP4) water channels are modulated by vasopressin V1a receptors, we examined the edema-reducing properties of the selective V1a receptor antagonist, SR49059, following middle cerebral artery occlusion (MCAO). Male Sprague-Dawley rats were randomly assigned to sham procedure, vehicle, or SR49059 infusion at different dosages (each n = 6,480 microL/hr, 640 microL/hr, 720 microL/hr) and starting 60 minutes before or after MCAO. After a 2-hour period of ischemia and 2 hours of reperfusion, the animals were sacrificed for assessment of brain water content, sodium, and potassium concentration. Statistics were performed using an ANOVA followed by a Tukey post hoc analysis. SR049059 treatment reduced brain water content in the infarcted area given at 640 microL/hr (p = 0.036), 720 microL/hr 60 minutes before (p = 0.002) or 60 minutes after (p = 0.005) MCAO. The consecutive sodium shift into the brain was prevented (p = 0.001), while the potassium loss was inhibited only by pre-treatment (p = 0.003). These findings imply that in ischemia-induced brain edema, the selective V1a receptor-antagonist SR49059 inhibits brain edema and the subsequent sodium shift into brain. This substance offers a new avenue in brain edema treatment and prompts further study into AQP4 modulation.

Modulation of AQP4 expression by the protein kinase C activator, phorbol myristate acetate, decreases ischemia-induced brain edema.

The protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), is known to interact with aquaporin-4 (AQP4), a water-selective transporting protein abundant in astrocytes and ependymal cells, that has been found to decrease osmotically-induced swelling. The purpose of this study was to examine whether PMA given at different time points following focal ischemia induced by middle cerebral artery occlusion (MCAO) reduces brain edema by AQP4 modulation. Male Sprague-Dawley rats were randomly assigned to sham procedure, vehicle, or PMA infusion (230 microg/kg), starting either 60 minutes before, or 30 or 60 minutes after MCAO (each group n = 12). After a 2-hour period of ischemia and 2 hours of reperfusion, the animals were sacrificed for assessment of brain water content, sodium, and potassium concentrations. AQP4 expression was assessed by immunoblotting. Statistical analysis was performed by ANOVA followed by Tukey's post hoc test. PMA treatment significantly reduced brain water content concentration in the infarcted area when started before or 30 minutes post-occlusion (p < 0.001, p = 0.022) and prevented the subsequent sodium shift (p < 0.05). Furthermore, PMA reduced ischemia-induced AQP4 up-regulation (p < 0.05). Attenuation of the ischemia-induced AQP4 up-regulation by PMA suggests that the reduction in brain edema formation following PMA treatment was at least in part mediated by AQP4 modulation.

Intramedullary screw fixation of Jones fractures.

BACKGROUND: Jones fractures of the fifth metatarsal can be stabilized using intramedullary screw fixation techniques. A range of screw diameters from 4.5 mm to 6.5 mm can be used, but the optimal screw for this procedure has yet to be defined. In clinical practice, we have observed that failure is more likely when smaller diameter screws are used. METHODS: Experimental Jones fractures were created in 23 pairs of human cadaver fifth metatarsals, which were fixed using either 5.0 mm or 6.5 mm screws. Fracture stiffness and pull-out strengths were measured for either screw type and their relationships with bone mineral density and medullary canal diameter were determined. RESULTS: There was no significant difference in the bending stiffness of fractures stabilized with 5.0 mm and 6.5 mm screws; however, different mechanisms of failure were noted for either screw type. Poor thread purchase within the medullary canal was noted with the 5.0 mm screws, while excellent purchase was noted with 6.5 mm screws. Pull-out strength testing revealed significantly higher pullout strengths for the larger 6.5 mm screws. There was no significant difference in bone mineral density or medullary canal diameter between right and left metatarsals. CONCLUSIONS: Fifth metatarsals can often accommodate a 6.5 mm screw for the stabilization of Jones fractures. Larger diameter screws did not result in greater fracture stiffness in our model, but did result in significantly greater pull-out strengths. CLINICAL RELEVANCE: Larger diameter screws may be more appropriate for intramedullary screw fixation of Jones fractures.

Regional material properties of the human hip joint capsule ligaments.

The hip joint capsule functions to constrain translation between the femur and acetabulum while allowing rotational and planar movements. Despite the crucial role it plays in the pathogenesis of hip instability, little is known about its biomechanical properties. The goal of this study was to determine the regional material properties of the iliofemoral and ischiofemoral ligaments of the capsule. Ten human cadaveric specimens of each ligament were tested to failure in tension. The stress at failure, strain at failure, strain energy density at failure, toe- and linear-region elastic moduli, and the Poisson's ratio were measured for each ligament. The strain to failure was greatest in the ischiofemoral ligament, while no significant difference was noted in failure stress by region or ligament. The Young's moduli of elasticity ranged from 76.1 to 285.8 MPa among the different ligaments, and were generally consistent with properties previously reported for the shoulder capsule. The elastic moduli and strain energy density at failure differed by region. No significant differences in Poisson's ratio were found by region or ligament. The average Poisson's ratio was approximately 1.4, consistent with anisotropic behavior of ligamentous tissues. Understanding the material properties of the hip capsule may help the orthopaedic surgeon better understand normal ligament function, and thereby choose a surgical approach or strategy of repair. Furthermore, knowledge of the normal mechanical function of the hip capsule ligaments could assist in the evaluation of the success of a repair.

Stiffness of simulated radial neck fractures fixed with 4 different devices.

We performed a structural investigation of several fixation devices for radial head and neck fixation. Fourteen pairs of fresh-frozen human elbows were used to simulate unstable radial neck fractures fixed with each of the following plates: 2.0-mm T-plate, 2.0-mm blade plate, 2.7-mm T-plate, and 2.7-mm T-plate modified with a fixed-angle blade. The plate constructs were axially loaded in compression with a materials testing machine, and stiffness was calculated from a load-deformation curve. Through use of paired comparisons, the average stiffness of the modified 2.7-mm plate was found to be significantly greater than that of either 2.0-mm plate, whereas a trend was observed for increased stiffness of the modified 2.7-mm T-plate in comparison with the standard 2.7-mm T-plate. The results indicate that two important variables affecting construct stiffness are plate thickness and incorporation of a fixed-angle blade. Given these findings, the addition of a fixed blade to the 2.7-mm plate may improve the stability of fixation of comminuted radial neck fractures.

Validity of photoelastic strain measurement on cadaveric proximal femora.

Rosette strain gages indicate shear and principal strains at specific points, whereas photoelastic coatings provide shear strain information over a broad area. Information regarding bone loading and load transfer from a prosthetic implant to adjacent bone can be obtained using either strain-measuring technique on loaded femora. This study compared proximal femoral strains derived from photoelastic coatings to those obtained from rosette strain gages applied directly to the bone in order to determine the relationships between photoelastic shear strains and rosette shear and principal strains. Photoelastic shear strains underestimated rosette shear strains and exceeded the larger of the rosette principal strains. Principal strains derived from photoelastic coatings augmented with strain separator gages underestimated their rosette counterparts in most instances. Correlation was strong and nearly linear for all measures, indicating that photoelastic coatings can accurately express proportional strain changes despite imperfect agreement in absolute strain magnitudes. The best agreement between absolute strain magnitudes occurred in the proximal medial, or calcar, region. Understanding the relationships between the various measures obtained using the two strain measurement methods will allow more accurate estimates of actual strains to be made from photoelastic coatings.

Comparison of soccer shin guards in preventing tibia fracture.

The goal of this study was to evaluate the effectiveness of a number of shin guards in protecting against tibia fracture in soccer players. A secondary purpose was to determine the relationship between the material and structural differences in shin guard design and the protection provided. Twenty-three commercially available shin guards were tested on a model leg containing a synthetic tibia that had been calibrated against human cadaver specimens. Each guard was categorized into one of four material types: plastic (N = 9), fiberglass (N = 6), compressed air (N = 4), and Kevlar (N = 4). The maximum combined force at the ends of the tibia, the principal strain on the posterior side of the tibia, and the contact time of the impact were measured using a drop track impact simulation. Shin guards provided significant protection from tibia fracture at all drop heights. The average guard reduced force by 11% to 17% and strain by 45% to 51% compared with the unguarded leg. At the higher drop heights, material composition and structural characteristics of the shin guards showed significant differences in protective abilities. These findings indicate that all shin guards provide some measure of protection against tibia fracture, although the level of protection may vary significantly among the different guards.

Fixation of three-part proximal humeral fractures: a biomechanical evaluation.

OBJECTIVES: To examine the biomechanical stability of three constructs currently used for the management of three-part proximal humerus fractures. Tension band wires (TBW) with supplemental Enders nails, modified cloverleaf plate and screws, and intramedullary (IM) nailing with proximal and distal interlocks were tested to determine relative stability. DESIGN: A reproducible three-part fracture was made in fresh-frozen stripped proximal humeri. The fracture was stabilized using TBW/Enders nail (n = 6), plate/screws (n = 5), or IM nailing (n = 5). MAIN OUTCOME MEASUREMENTS: Mechanical testing was performed with a small preload followed by deflection of five millimeters at a rate of one millimeter per second in flexion, extension, and varus and valgus relative to the humeral shaft. A load-displacement curve was obtained. Torsional testing was performed in internal and external rotation, and torque-rotation curves were recorded. RESULTS: In cantilever bending, the plate/screws construct and the IM nail construct were superior to the TBW/Enders nail construct for all parameters except extension. There was no statistically significant difference between the IM nail and the plate/screws groups. Torsional stiffness testing revealed that the plate/screws and the IM nail were superior to the TBW/Enders nail construct. There was no statistical difference between the IM nail and the plate/screws groups. CONCLUSIONS: In a cadaveric model of three-part proximal humerus fractures stripped of soft tissue, plate/screws fixation and IM nailing provide greater torsional and bending stiffness than does fixation with TBW/Enders nail. There was no statistically significant difference in torsional or bending stiffness between IM nailing with interlocks and plate/screws fixation in this model.

Risk of avulsion of the Achilles tendon after partial excision for treatment of insertional tendonitis and Haglund's deformity: a biomechanical study.

Surgical treatment of posterior heel pain caused by insertional (calcific) Achilles tendonitis or retrocalcaneal bursitis includes resection of diseased tendon or exostectomy. Currently, no guidelines exist to determine how much tendon may be excised without risking rupture of the Achilles tendon. Anatomic dissections revealed the average height of the insertion measured 19.8 mm (range, 13-25 mm). Average width at the proximal aspect of the insertion measured 23.8 mm (range, 17-30 mm) and distally measured 31.2 (range, 25-38 mm). To assess the risk of avulsion, the tendon insertion was partially released in 25% increments of its measured height or width by one of the four methods: (1) from superior to inferior, (2) from the central portion outward, (3) from medial to lateral, and (4) from lateral to medial. Repeated cyclic loading of body weight x 3 was applied, and, if the tendon remained intact, the next 25% increment was released. This process was repeated until failure occurred. Failure occurred in all specimens by an oblique intratendonous separation or shear between the intact portion remaining on the calcaneus and the resected fibers remaining in the clamp. Fibers inserting into the bone did not avulse. Superior-to-inferior resection was found to be superior to the other three methods with eight of nine specimens remaining intact after 75% resection. We therefore conclude that superior-to-inferior offers the greatest margin of safety when performing partial resections of the Achilles insertion, and as much as 50% of the tendon may be resected safely.

The effect of hip stem material modulus on surface strain in human femora.

Human femora were used to compare the changes in bone surface strain resulting from decreasing the material modulus of a collarless hip stem to determine whether a highly elastic stem increased bone loading. Three substrate materials were tested: titanium (modulus of elasticity 110 GPa), carbon fiber composite (modulus of elasticity 52 GPa), and polymethylmethacrylate (PMMA, modulus of elasticity of 1.9 GPa). Two separate analyses were performed in which femora were implanted randomly with one of the three stem types. Results showed that assembly strains did not differ significantly among different materials. There was a large strain reduction in the proximal region of the femora for all stem substrates relative to the intact femur. Although there was statistically greater surface shear strain as the material modulus decreased, the PMMA stem did not substantially increase bone loading.

A biomechanical comparison of intramedullary nail and crossed lag screw fixation for tibiotalocalcaneal arthrodesis.

This study compared the mechanical bending and torsional properties of intramedullary nail fixation and lag screw fixation for tibiotalocalcaneal arthrodesis. Seven matched pairs of human cadaver lower extremities were studied, with one hindfoot in each pair stabilized with a 12 mm x 150 mm interlocked intramedullary nail inserted retrograde across the subtalar and ankle joints. The contralateral hindfoot was stabilized with two crossed 6.5 mm cannulated screws inserted across both the ankle and subtalar joints. Specimens were subjected to cantilever bending tests in plantarflexion, dorsiflexion, inversion, and eversion and to torsional tests in internal and external rotation. The intramedullary nail construct was significantly (P < 0.05) stiffer than the crossed lag screw construct in all four bending directions and both rotational directions: plantarflexion (nail, 42.8 N/mm; screws, 16.4 N/mm; P = 0.0003), dorsiflexion (nail, 43.0 N/mm; screws, 10.3 N/mm; P = 0.0005), inversion (nail, 37.7 N/mm; screws, 12.3 N/mm; P = 0.0024), eversion (nail, 35.4 N/mm; screws, 10.8 N/mm; P = 0.0004), internal rotation (nail, 1.29 N-m/degree; screws, 0.82 N-m/degree; P = 0.01), external rotation (nail, 1.35 N-m/degree; screws, 0.44 N-m/degree; P = 0.0001). Intramedullary fixation is biomechanically stiffer than crossed lag screws in all bending and torsional directions tested and therefore this construct may aid in maintaining alignment of the hindfoot during union and may help increase fusion rate through increased stability of the internal fixation.

Effects of coronally slotted femoral prostheses on cortical bone strain.

The photoelastic method was used to assess the effects on femoral cortical strain of total hip arthroplasty cementless femoral prostheses containing distal coronal slots. Eight cadaveric femurs were tested, although three were eliminated secondary to fractures. Loaded and unloaded cortical strains were determined at 72 points on the implanted femoral cortex and compared with the values obtained in the intact femur. Three different prostheses were sequentially implanted, in a random order, into each femur. The prostheses consisted of a standard solid stem, an identical stem with a coronal slot in its distal one fourth, and an identical stem with a coronal slot in its distal one half. The slotted stems did not enhance axial load transfer to the proximal medial femur but did result in increased proximal medial assembly strains and statistically significant (P < .05) decreased anterior and posterior assembly strains. The increased proximal medial assembly strains are hypothesized to enhance proximal medial femoral loading, while the decreased anterior and posterior assembly strains may minimize operative implantation fractures.

Dimensions of the intercondylar notch of the knee.

This study evaluates the three-dimensional contour of the intercondylar notch of the knee along its entire length. Forty-one distal femora, from human cadavers with a mean age of 45 years (range: 23 to 70 years) at the time of death were studied. The specimens were selected for the absence of previous surgery or degenerative changes including osteophyte formation. Measurements were taken from a cast of the distal femur. Transverse sections of the cast were cut every 3 mm in a plane perpendicular to the long axis of the femur. Within this plane, the epicondylar width, the condylar height, the notch height, and the minimum and maximum width of the notch were measured. The ratios between these measurements were calculated and subjected to analysis of variance. The notch width increased gradually from a mean of 1.8 cm at the distal aspect to a mean of 2.3 cm at the most proximal portion. The notch height increased from a mean value of 1.8 cm at the distal-most portion to a maximum of 2.4 cm at 1.8 cm from the distal-most portion of the notch. The height then decreased to a mean value of 1.3 cm at the most proximal portion of the notch. The epicondylar width:notch width ratio ranged from 4.70 distally to 4.25 proximally. These results indicate that the notch is narrowest distally and widens proximally, and the notch height is greatest in the midportion and decreases proximally and distally.

Meniscal fixation with an absorbable staple. An experimental study in dogs.

An absorbable staple for meniscal fixation was developed and evaluated in an in vivo canine study. The staple consisted of two rigid barbed legs, made of a copolymer of polyglycolic acid and polylactic acid, connected by a flexible suture made of the same absorbable material. The staple was developed for arthroscopic use, eliminating the risk of nerve or vascular injuries associated with suture fixation. Eighty-two mongrel dogs underwent meniscal repair in this study, which was performed in two sequential parts. An incision was made in the medial meniscus at the peripheral third and was fixed with either the staple or with a single 3-0 PDS suture. The animals from the first part of the study, in which the biocompatibility of a prototype staple design, was evaluated were sacrificed at 3 days, 2 weeks, 6 weeks, 3 months, and 9 months. Those from the second part of the study, in which an improved staple design of the same material, was evaluated were sacrificed at 6 weeks, 4 months, and 1 year. The operated menisci were either examined histologically or were mechanically tested for tensile strength. Absorption of the staple began by 3 months and was almost complete by 1 year. Mechanically, the staple provided greater tensile strength augmentation of the meniscus than suture fixation for up to 4 months. In the long term, there was no difference between the staple and suture in enhancement of healing.

Comparison of distal humerus fracture fixation: a biomechanical study.

Few biomechanical studies have been done evaluating the rigidity of internal fixation constructs for distal humerus fractures. We assessed the bending and torsional stiffness of five commonly used multiple plate constructs. Plates were applied in three positions: medially, along the medial supracondylar column; laterally, along the lateral supracondylar column; or posterolaterally, extending distally to the capitellum. Each specimen was randomly assigned to one of five construct groups. All plated specimens were stiffer in the frontal plane as compared with the sagittal plane and, when compared with intact specimens, showed a disproportionate decrease in sagittal plane stiffness. Constructs 1 and 5 had significantly greater relative bending stiffness in the sagittal plane than constructs 3 and 4. Construct 4 had the lowest relative bending stiffness in the frontal plane. This reached statistical significance when compared with constructs 2 and 5. There was no significant difference in the torsional stiffness of the five constructs. We conclude that the multiple plate constructs offered significantly less bending stiffness than the intact specimens, with a particular deficiency in the sagittal plane. The triple-plated construct (construct 5) did not confer greater stiffness and was technically difficult to implant. The medial pelvic reconstruction plate combined with the posterolateral DCP (construct 1) provided the greatest sagittal plane stiffness, in addition to comparable frontal plane and torsional stiffness. We recommend its use in the treatment of fractures of the distal humerus.

Use of bone compaction in total knee arthroplasty.

This study compared the effects of bone preparation on tibial stem stability in total knee arthroplasty. Six pairs of fresh-frozen tibias underwent implantation of an 18 x 75-mm press-fit stem (minus the tibial tray). The standard press-fit technique was performed creating a cavity 17 mm in diameter. For the bone compaction technique, stainless-steel dilators were machined ranging in diameter from 6 to 16 mm in 2-mm increments. The technique consisted of using the dilators and a mallet to create a compacted tunnel in a sequential manner to 16 mm in diameter followed by implantation of the stem. The specimens were mounted on a materials testing machine and loads were applied in both planes: anteroposterior and mediolateral. A preconditioning load of 100 N was applied followed by a second 100-N load from which the stiffness (N/mm) of implantation was calculated. The stability of the tibial stems implanted by compaction averaged 84.7% greater when compared with the press-fit stems (P < .017 by multivariate analysis).

The role of fatigue in susceptibility to acute muscle strain injury.

We investigated the role of fatigue in muscle strain injuries using the extensor digitorum longus muscles of 48 rabbits. The muscles of the rabbits were fatigued by 25% or 50% then stretched to failure and compared with the contralateral controls. Three rates of stretch were used. The force to muscle failure was reduced in the fatigued leg in all groups (range, 93% to 97.4% compared with the controls). The change in muscle length in the fatigue groups was not different from the controls. The amount of energy absorbed in the fatigued muscle was 69.7% to 92% that of the energy absorbed in the control muscle. The lowest energy absorption occurred in muscles that were more fatigued. In eight additional rabbits, fatigued extensor digitorum longus muscles were compared with submaximally stimulated muscles with the equivalent contractile properties, and no difference was seen. Muscles subjected to strains are frequently injured under high-intensity eccentric loading conditions. Under these conditions, muscles absorb energy and provide control and regulation of limb movement. Our data showed that muscles are injured at the same length, regardless of the effects of fatigue. However, fatigued muscles are able to absorb less energy before reaching the degree of stretch that causes injuries.

Cryopreserved anterior cruciate ligament allografts in a canine model.

This study was done to determine the clinical and biomechanical properties of cryopreserved anterior cruciate ligament allografts at 3, 6, 9, and 24 months after transplantation. A companion study of autografts was done to evaluate the effects of the surgical procedure and preservation on the tissue. The knee joints of 69 mongrel dogs (allograft n = 34, autograft n = 35) weighing 17 kg to 25 kg were grafted. Biomechanical results showed that maximum load was less in allografts than in autografts at each time interval. Deformation and slope were not significantly different between allograft and autograft. An apparent delay in revascularization and cellular repopulation was found in allografts compared with autografts, and collagen type I/type III ratios were similar in both grafts. DNA analysis indicated complete replacement of DNA in the graft by the host. Allografts provide adequate functional stability for daily activities in the canine model up to 2 years after transplantation. Biomechanical properties were relatively poor in allografts, which may lead to failure under more strenuous activity. The biologic similarity to autografts may indicate future remodeling potential.

Load tolerance of tibial plateau depressions reinforced with a cluster of K-wires.

The efficacy of subchondral Kirschner wires in enhancing load tolerance of the tibial plateau articular cartilage was examined in a biomechanical study of cadaveric tibias. Seven patterns of K-wires were evaluated under axial loading equivalent to the maximum loading of the knee during normal gait. Subchondral K-wire reinforcement of tibial plateau depressions significantly enhanced load tolerance. This suggests that a subchondral cluster of K-wires in the treatment of tibial plateau fractures may protect the articular cartilage from the loss of reduction resulting from the forces applied to the knee during non-weight-bearing motion.