In-situ mechanical behavior and slackness of the anterior cruciate ligament at multiple knee flexion angles.

In this study the in-situ tensile behavior and slackness of the anterior cruciate ligament (ACL) was evaluated at various knee flexion angles. In four cadaveric knees the ACL was released at the tibial insertion, after which it was re-connected to a tensiometer. After pre-tensioning (10 N) the ACL in full-extension, the knee was flexed from 0° to 150° at 15° increments, during which the ACL tension was measured. At each angle the ACL was subsequently elongated and shortened under displacement control, while measuring the ACL tension. In this manner, the pre-tension or the slackness, and the mechanical response of the ACL were measured. All ACL's displayed a higher tension at low (0°-60°) and high (120°-150°) flexion angles. The ACL slackness depended on flexion angle, with the highest slackness found at 75°-90°. Additionally, the ACL stiffness also varied with flexion angle, with the ACL behaving stiffer at low and high flexion angels. In general, the ACL was stiffest at 150°, and most compliant at 90°. The results of this study contribute to understanding the mechanical behavior of the ACL in-situ, and may help tuning and validating computational knee models studying ACL function.

Material properties of the human posterior knee capsule.

BACKGROUND: There is considerable interest to develop accurate subject-specific biomechanical models of the knee. Most of the existing models currently do not include a representation of the posterior knee capsule. In order to incorporate the posterior capsule in knee models, data is needed on its mechanical properties. OBJECTIVE: To quantify the mechanical properties of the human posterior knee capsule through semi-static tensile tests. METHODS: Fifteen posterior knee capsule specimens (5 knees, 3 male, 2 female; age 79.2±7.9 years) were used to perform tensile tests. A medial, central and lateral specimen was taken from each knee. The cross-sectional area was measured, after which semi-static tensile tests were performed to quantify the material properties. RESULTS: The stiffness of the capsule was randomly distributed over the regions. The global Young's modulus and yield strength was 8.58±10.77 MPa and 1.75±1.89 MPa, respectively. A strong correlation (ρ=0.900) was found between Young's modulus and yield strength. The location of failure was not associated with smallest cross-sectional area or highest strain. CONCLUSIONS: The results suggest that the posterior knee capsule does not have a systematic (medial-central-lateral) distribution of material properties. The posterior capsule may play an important role in knee joint mechanics, particularly when in hyper extension.

Generating finite element models of the knee: How accurately can we determine ligament attachment sites from MRI scans?

In this study, we evaluated the intra- and inter-observer variability when determining the insertion and origin sites of knee ligaments on MRI scan images. We collected data of five observers with different backgrounds, who determined the ligament attachment sites in an MRI scan of a right knee of a 66-year-old male cadaver donor. We evaluated the intra- and inter-observer differences between the ligament attachment center points, and also determined the differences relative to a physical measurement performed on the same cadaver. The largest mean intra- and inter-observer differences were 4.30mm (ACL origin) and 16.81mm (superficial MCL insertion), respectively. Relative to the physical measurement, the largest intra- and inter-observer differences were 31.84mm (superficial MCL insertion) and 23.39mm (deep MCL insertion), respectively. The results indicate that, dependent on the location, a significant variation can occur when identifying the attachment site of the knee ligaments. This finding is of particular importance when creating computational models based on MRI data, as the variations in attachment sites may have a considerable effect on the biomechanical behavior of the human knee joint.

[Metabolism of beta-adrenergic substances. Therapeutic implications]. / Métabolisme des substances bêta-adreénergiques. Implications thérapeutiques.

The metabolism of the main beta-adrenoceptor stimulants which are not catechol derivatives involves conjugation with glucuronic or sulphuric acids in several animal species and conjugation with sulphuric acid in man. These drugs are not metabolized by MAO like isoproterenol or by COMT like the catechol derivatives: isoproterenol, trimetoquinol, hexoprenaline and rimiterol. Sulphate conjugation, in man, increases with the number of hydroxy groups. For salbutamol, pirbuterol, terbutaline and fenoterol, about 30%, 30%, 15% and 10% are respectively present in plasma as the unchanged active compound. Clenbuterol, a new specific beta 2-adrenoceptor stimulant, is a 4-amino-3,5 dichloro-benzene derivative and cannot be conjugated. It is cleared from the body mainly by the renal route (43% of the administered dose) and has eight minor metabolites, identical in several animal species and in man. Tulobuterol with no hydroxy substitute does not undergo conjugation, but is metabolized to 4-hydroxy tulobuterol. This metabolite is shown to be eight times more potent than tulobuterol. Metabolism depends greatly upon the route of administration: intravenous, subcutaneous, oral, by aerosol or instillation into the bronchial tree. Conjugation or COMT inactivation can take place in the gut wall (terbutaline), in lungs (isoproterenol, terbutaline, rimiterol) or by hepatic first-pass. These processes decrease the amount of drug reaching the blood and the receptor sites. Metabolism in the lung is important for ibuterol (terbutaline diisobutyrate), which is more lipophilic than terbutaline and spreads throughout tissues where it is hydrolyzed to active terbutaline. Biotransformations are determined by environmental or genetic factors and by the associated therapy and can change dramatically from one patient to another (interindividual variability) or for the same patient by multiple dosing (intra-individual variability). These differences in the rates of the metabolism can explain, partly, the differences observed in the response to beta-adrenoceptor stimulants by responder or non-responder patients. Decision about a therapeutic dosage regiment involves the choice of the drug, of the route of administration and of the dose. This choice is made on the basis of the dose/response relationship. In the kinetic approach, pharmacokinetic data obtained after a single dose facilitate the development of an appropriate dosage regimen.