The differences in shape between central aortic pressure (P(Ao)) and flow waveforms have never been explained satisfactorily in that the assumed explanation (substantial reflected waves during diastole) remains controversial. As an alternative to the widely accepted frequency-domain model of arterial hemodynamics, we propose a functional, time-domain, arterial model that combines a blood conducting system and a reservoir (i.e., Frank's hydraulic integrator, the windkessel). In 15 anesthetized dogs, we measured P(Ao), flows, and dimensions and calculated windkessel pressure (P(Wk)) and volume (V(Wk)). We found that P(Wk) is proportional to thoracic aortic volume and that the volume of the thoracic aorta comprises 45.1 +/- 2.0% (mean +/- SE) of the total V(Wk). When we subtracted P(Wk) from P(Ao), we found that the difference (excess pressure) was proportional to aortic flow, thus resolving the differences between P(Ao) and flow waveforms and implying that reflected waves were minimal. We suggest that P(Ao) is the instantaneous summation of a time-varying reservoir pressure (i.e., P(Wk)) and the effects of (primarily) forward-traveling waves in this animal model.

Corticosteroids are used in musculoskeletal diseases, and offer patient relief. Injections of corticosteroids are recommended for management of osteoarthritis (OA). Current data have shown the role of corticosteroids in ameliorating pain. We hypothesized that repeated intra-articular injections of high dose dexamethasone would protect the cartilage from damage in a post-traumatic model of OA. Eighteen female New Zealand White rabbits were used. Twelve underwent surgery to induce OA; six of them received intraarticular injections of dexamethasone every 3 days for 3 weeks. The other six rabbits served as operated controls. Six additional rabbits served as non-operated controls. All animals were euthanized 3 weeks post-surgery. Knees were assessed grossly. Cartilage, synovium, and fat pad were assessed histologically. Synovium and fat pad were analyzed with qPCR and Western blots. Surgical controls had cartilage damage which was supressed with dexamethasone. Dexamethasone significantly decreased synovial expression of interleukin1b and collagen I, and a trend to decrease synovial matrix metalloproteinase3 expression. There were also significantly lower levels of interleukin-1b protein with dexamethasone treatment. Dexamethasone significantly decreased fat pad expression of matrix metalloproteinase13, basic fibroblast growth factor, and interleukin8, and a trend to decrease matrix metalloproteinase3 and transforming growth factorb expression. Dexamethasone decreased joint inflammation and joint tissue degradation and was chondroprotective in this unique model of PTOA. ß

SUMMARYHeterotopic tendon mineralization (ossification or calcification), which may be a feature of tendinopathy or which may develop following surgical trauma (repair or graft harvest), has not received much attention. The purpose of this article is to review the prevalence, mechanisms and consequences of heterotopic tendon mineralization and to identify the gaps in our current understanding. We focus on endochondral heterotopic ossification and draw on knowledge of the mechanisms of this process in other tissues and conditions. Finally, we introduce a novel murine Achilles tendon needle injury model, which will enable us to further study the mechanisms and biomechanical consequences of tendon mineralization.

Injured ligaments heal with scar tissue, which has mechanical properties inferior to those of normal ligament, potentially resulting in re-injury, joint instability, and subsequent degenerative arthritis. In ligament scars, normal large-diameter collagen fibrils have been shown to be replaced by a homogenous population of small collagen fibrils. Because collagen is a major tensile load-bearing matrix element and because the proteoglycan decorin is known to inhibit collagen fibrillogenesis, we hypothesized that the restoration of larger collagen fibrils in a rabbit ligament scar, by down-regulating the proteoglycan decorin, would improve the mechanical properties of scar. In contrast to sense and injection-treated controls, in vivo treatment of injured ligament by antisense decorin oligodeoxynucleotides led to an increased development of larger collagen fibrils in early scar and a significant improvement in both scar failure strength (83-85% improvement at 6 weeks; p < 0.01) and scar creep elongation (33-48% less irrecoverable creep; p < 0.03) under loading. This is the first report that in vivo manipulation of collagen fibrillogenesis improves tissue function during repair processes with gene therapy. These findings not only suggest the potential use of this type of approach to improve the healing of various soft tissues (skin, ligament, tendon, and so on) but also support the use of such methods to better understand specific structure-function relationships in scars.

Molecular analysis of ligaments and ligament scars, combined with ongoing morphological and biomechanical studies of ligament structure and function, will ultimately reveal which factors can be manipulated clinically to optimize the restoration of normal ligament properties after ligament injuries. Further studies on the mechanisms of ligament healing, genetic markers of repair, and gender-specific differences in ligament repair responses are required.

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The parameters of wave intensity analysis are calculated from incremental changes in pressure and velocity. While it is clear that forward- and backward-traveling waves induce incremental changes in pressure, not all incremental changes in pressure are due to waves; changes in pressure may also be due to changes in the volume of a compliant structure. When the left ventricular ejects blood rapidly into the aorta, aortic pressure increases, in part, because of the increase in aortic volume: aortic inflow is momentarily greater than aortic outflow. Therefore, to properly quantify the effects of forward or backward waves on arterial pressure and velocity (flow), the component of the incremental change in arterial pressure that is due only to this increase in arterial volume--and not, fundamentally, due to waves--first must be excluded. This component is the pressure generated by the filling and emptying of the reservoir, Otto Frank's Windkessel.

In normal daily activity, ligaments are probably subjected to repeated loading rather than to repeated deformation. The viscoelastic response to repeated loading is creep; this effect has significance for ligament reconstructions, which potentially "stretch out" over time. However, most experimental studies have examined the viscoelastic response to repeated deformation, stress relaxation. We hypothesized that the creep of a ligament could be predicted from its stress-relaxation behaviour. Left and right medial collateral ligaments of eight skeletally mature rabbits were subjected to either creep or stress-relaxation testing under comparable conditions. The time-dependent increase in strain (creep) and reduction in load (relaxation) from the tests were modelled with use of the quasilinear viscoelastic theory and generalized standard linear solid modelling. Ligaments were found to creep distinctly less than would be predicted from relaxation tests. Although the reason for this behaviour remains unknown, we speculate that it is due to the progressive recruitment of collagen fibres during creep.