Patient-specific non-invasive estimation of the aortic blood pressure waveform by ultrasound and tonometry.

BACKGROUND AND OBJECTIVE: Aortic blood pressure (ABP) is a more effective prognostic indicator of cardiovascular disease than peripheral blood pressure. A highly accurate algorithm for non-invasively deriving the ABP wave, based on ultrasonic measurement of aortic flow combined with peripheral pulse wave measurements, has been proposed elsewhere. However, it has remained at the proof-of-concept stage because it requires a priori knowledge of the ABP waveform to calculate aortic pulse wave velocity (PWV). The objective of this study is to transform this proof-of-concept algorithm into a clinically feasible technique. METHODS: We used the Bramwell-Hill equation to non-invasively calculate aortic PWV which was then used to reconstruct the ABP waveform from non-invasively determined aortic blood flow velocity, aortic diameter, and radial pressure. The two aortic variables were acquired by an ultrasound system from 90 subjects, followed by recordings of radial pressure using a SphygmoCor device. The ABPs estimated by the new algorithm were compared with reference values obtained by cardiac catheterization (invasive validation, 8 subjects aged 62.3 ± 12.7 years) and a SphygmoCor device (non-invasive validation, 82 subjects aged 45.0 ± 17.8 years). RESULTS: In the invasive comparison, there was good agreement between the estimated and directly measured pressures: the mean error in systolic blood pressure (SBP) was 1.4 ± 0.8 mmHg; diastolic blood pressure (DBP), 0.9 ± 0.8 mmHg; mean blood pressure (MBP), 1.8 ± 1.2 mmHg and pulse pressure (PP), 1.4 ± 1.1 mmHg. In the non-invasive comparison, the estimated and directly measured pressures also agreed well: the errors being: SBP, 2.0 ± 1.4 mmHg; DBP, 0.8 ± 0.1 mmHg; MBP, 0.1 ± 0.1 mmHg and PP, 2.3 ± 1.6 mmHg. The significance of the differences in mean errors between calculated and reference values for SBP, DBP, MBP and PP were assessed by paired t-tests. The agreement between the reference methods and those obtained by applying the new approach was also expressed by correlation and Bland-Altman plots. CONCLUSION: The new method proposed here can accurately estimate ABP, allowing this important variable to be obtained non-invasively, using standard, well validated measurement techniques. It thus has the potential to relocate ABP estimation from a research environment to more routine use in the cardiac clinic. SHORT ABSTRACT: A highly accurate algorithm for non-invasively deriving the ABP wave has been proposed elsewhere. However, it has remained at the proof-of-concept stage because it requires a priori knowledge of the ABP waveform to calculate aortic pulse wave velocity (PWV). This study aims to transform this proof-of-concept algorithm into a clinically feasible technique. We used the Bramwell-Hill equation to non-invasively calculate aortic PWV which was then used to reconstruct the ABP waveform. The ABPs estimated by the new algorithm were compared with reference values obtained by cardiac catheterization or a SphygmoCor device. The results showed that there was good agreement between the estimated and directly measured pressures. The new method proposed can accurately estimate ABP, allowing this important variable to be obtained non-invasively, using standard, well validated measurement techniques. It thus has the potential to relocate ABP estimation from a research environment to more routine use in the cardiac clinic.

Elastase treatment of tendon specifically impacts the mechanical properties of the interfascicular matrix.

The tendon interfascicular matrix (IFM) binds tendon fascicles together. As a result of its low stiffness behaviour under small loads, it enables non-uniform loading and increased overall extensibility of tendon by facilitating fascicle sliding. This function is particularly important in energy storing tendons, with previous studies demonstrating enhanced extensibility, recovery and fatigue resistance in the IFM of energy storing compared to positional tendons. However, the compositional specialisations within the IFM that confer this behaviour remain to be elucidated. It is well established that the IFM is rich in elastin, therefore we sought to test the hypothesis that elastin depletion (following elastase treatment) will significantly impact IFM, but not fascicle, mechanical properties, reducing IFM resilience in all samples, but to a greater extent in younger tendons, which have a higher elastin content. Using a combination of quasi-static and fatigue testing, and optical imaging, we confirmed our hypothesis, demonstrating that elastin depletion resulted in significant decreases in IFM viscoelasticity, fatigue resistance and recoverability compared to untreated samples, with no significant changes to fascicle mechanics. Ageing had little effect on fascicle or IFM response to elastase treatment. This study offers a first insight into the functional importance of elastin in regional specific tendon mechanics. It highlights the important contribution of elastin to IFM mechanical properties, demonstrating that maintenance of a functional elastin network within the IFM is essential to maintain IFM and thus tendon integrity. STATEMENT OF SIGNIFICANCE: Developing effective treatments or preventative measures for musculoskeletal tissue injuries necessitates the understanding of healthy tissue function and mechanics. By establishing the contribution of specific proteins to tissue mechanical behaviour, key targets for therapeutics can be identified. Tendon injury is increasingly prevalent and chronically debilitating, with no effective treatments available. Here, we investigate how elastin modulates tendon mechanical behaviour, using enzymatic digestion combined with local mechanical characterisation, and demonstrate for the first time that removing elastin from tendon affects the mechanical properties of the interfascicular matrix specifically, resulting in decreased recoverability and fatigue resistance. These findings provide a new level of insight into tendon hierarchical mechanics, important for directing development of novel therapeutics for tendon injury.

Elastin is Localised to the Interfascicular Matrix of Energy Storing Tendons and Becomes Increasingly Disorganised With Ageing.

Tendon is composed of fascicles bound together by the interfascicular matrix (IFM). Energy storing tendons are more elastic and extensible than positional tendons; behaviour provided by specialisation of the IFM to enable repeated interfascicular sliding and recoil. With ageing, the IFM becomes stiffer and less fatigue resistant, potentially explaining why older tendons become more injury-prone. Recent data indicates enrichment of elastin within the IFM, but this has yet to be quantified. We hypothesised that elastin is more prevalent in energy storing than positional tendons, and is mainly localised to the IFM. Further, we hypothesised that elastin becomes disorganised and fragmented, and decreases in amount with ageing, especially in energy storing tendons. Biochemical analyses and immunohistochemical techniques were used to determine elastin content and organisation, in young and old equine energy storing and positional tendons. Supporting the hypothesis, elastin localises to the IFM of energy storing tendons, reducing in quantity and becoming more disorganised with ageing. These changes may contribute to the increased injury risk in aged energy storing tendons. Full understanding of the processes leading to loss of elastin and its disorganisation with ageing may aid in the development of treatments to prevent age related tendinopathy.

The influence of swelling and matrix degradation on the microstructural integrity of tendon.

Tendon is multi-level fibre composite material, responsible for the transmission of forces from muscles to the skeleton. It is composed of a hierarchical arrangement of collagenous units surrounded by a proteoglycan-rich matrix, arranged to support strain transfer, and thus contribute to the mechanical behaviour of tendon. This study examines the effect of swelling and enzymatic degradation on structural integrity at different levels of the tendon hierarchy. Biochemical and microstructural analysis are used to examine the effects of incubation on the composition and swelling of the matrix, prior to a mechanical characterisation of sample integrity. Results indicated significant swelling of tendon fibrils and interfibrillar matrix after incubation in phosphate buffered saline, leading to a reduction in ultimate tensile load, with failure initiated between fibrils and sub-fibrils. In contrast, incubation with the enzyme chondroitinase ABC resulted in a total removal of glycosaminoglycan from the samples, and a subsequent reduction in the extent of swelling. These fascicles also demonstrated an increase in failure loads, with failure predominating between fibres. The findings from this work confirm the importance of the non-collagenous matrix components in controlling strain transfer within tendon structures. It also highlights the necessity to maintain samples within a suitable and controlled environment prior to testing.