Influence of age and of desmotropic drugs on the step phenomenon observed in rat skin

Summary Comprehensive analysis of the mechanical properties of rat skin revealed the step phenomenon. This particular observation was made after constant strain rate (analysis of stress strain curves) as well as after constant load (creep experiments). Relative low extensions or low loads were necessary to provoke the steps. In most cases two, sometimes three steps were observed. The step phenomenon was found mainly in skin strips punched out perpendicularly to the body axis. Probably some bonds in the fibrous network are broken giving way to additional elongation whereafter stronger links take over the stress. Since earlier studies demonstrated a pronounced influence of age and of desmotropic drugs on mechanical properties at ultimate load, e.g., tensile strength, ultimate modulus of elasticity, and ultimate strain, also the step phenomenon was studied under these conditions. In stress-strain experiments most of the steps were found at the ages of 2 and 4 months. Total stress loss and total work loss due to the steps were the highest at the age of 4 months. If, however, these values were calculated as percentage of ultimate values, the highest figures were found in young animals. Elongation gain due to the steps also showed a maximum at time of maturation, e.g., 4 months. Similar findings were achieved in creep experiments at medium load (200 g). After treatment with prednisolone acetate more steps and after treatment with d-penicillamine fewer steps were observed. In stress-strain experiments total stress loss and total work loss due to steps were more than twice as high than controls after prednisolone treatment and only one half after d-penicillamine. If calculated as percentage of ultimate stress or percentage of work input, these changes disappeared because of similar changes at ultimate load. However, elongation gain due to steps, which was not significantly influenced by prednisolone acetate but significantly decreased by d-penicillamine, showed the same changes when calculated as percentage of ultimate strain. Under all conditions the step phenomenon mainly influenced the extension parameters. The data presented here confirm earlier observations that mechanical properties at low loads or low and medium extensions show at least to some extent a different pattern under the influence of maturation and age and after treatment with desmotropic drugs compared to the mechanical parameters at ultimate load.     

Physiological responses during a T-piece weaning trial with a deflated tube

Rationale T-piece trials and spontaneous breathing trials through the tracheostomy tube are often used as weaning techniques. They are usually performed with the cuff inflated, which may increase the inspiratory load and/or influence the tidal volume generated by the patient. We assessed diaphragmatic effort during T-piece trials with or without cuff inflation.Settings Respiratory intensive care unitMethods We measured breathing pattern, transdiaphragmatic pressure (Pdi), the pressure-time product of the diaphragm, per minute (PTPdi/min) and per breath (PTPdi/b), and lung mechanics (lung compliance and resistance) in 13 tracheotomized patients ready for a weaning trial. V_T was recorded with respiratory inductive plethysmography (RIP-V_T) or pneumotachography PT-V_T). Patients completed two T-piece trials of 30 min each with or without the cuff inflated.Results RIP-V_T and PT-V_T values were similar with the cuff inflated, but PT-V_T significantly underestimated RIP-V_T when the cuff was deflated, and therefore the RIP-V_T was chosen as the reference method. The RIP-V_T was significantly greater and the Pdi and PTPdi/min significantly lower when the cuff was deflated than when it was inflated. The efficiency of the diaphragm, calculated by the ratio of PTPdi/b over RIP-V_T, was also improved, while no changes were observed in lung mechanics.Conclusions Diaphragmatic effort is significantly lower during a T-piece trial with a deflated cuff than when the cuff is inflated, while RIP-V_T is higher, so that the diaphragm's efficiency in generating tidal volume is also improved.Electronic supplementary material The electronic reference of this article is . The online full-text version of this article includes electronic supplementary material. This material is available to authorised users and can be accessed by means of the ESM button beneath the abstract or in the structured full-text article. To cite or link to this article you can use the above reference.     

Design of a novel MEMS platform for the biaxial stimulation of living cells

Micromechanical systems are increasingly being used as tools in biological applications, since their characteristic dimensions permit to operate at the same length scale of the structures under investigation. Here, we present a methodology for the design, fabrication and operation of a tool for the assessment of mechanical properties of single cells. In particular, we describe a microsystems platform to study bio-mechanical response of single living cells to in-plane biaxial stretching. The proposed device employs a new linkage design in order to obtain the displacement of the quadrants of a sliced circular plate in mutually-orthogonal directions using just one linear actuator. With this linkage geometry, the whole device has only one degree of freedom. This results in a very predictable and reliable mechanical behaviour, thereby allowing use a simple and easily available control electronics. Results of this study have relevance for the design of a powerful yet simple BioMEMS platform for the characterization of living cells as in-plane bi-axial loading simulated the conditions experienced by cells in vivo more realistically than a uniaxial stretching.     

Specific types of activated Factor XII increase following thrombolytic therapy with tenecteplase

Background Activated Factor XII (XIIa) is believed to participate in a number of pathophysiological processes including inflammation, thrombosis and fibrinolysis. Increasing XIIa levels following thrombolytic therapy have previously been reported. In contrast to other thrombolytics, tenecteplase (TNK-tpa) does not show paradoxical thrombin activation, indicating a lower procoagulant effect of this fibrin-selective thrombolytic agent. Recent research has demonstrated that in-vivo XIIa exists in a number of different types, and the aim of this study was to investigate plasma variations of different types of XIIa following thrombolytic treatment with TNK-tpa.Methods Citrated blood samples were obtained from 34 patients admitted with acute ST-elevation myocardial infarction (STEMI) treated with TNK-tpa. Samples were taken immediately prior to treatment, 30–90 min after and 4 days post-treatment. XIIa measurements were performed using 2 ELISA assays designed to preferentially measure different types of XIIa; XIIaA and XIIaR. Both assays utilised a monoclonal antibody 2/215, which is highly specific for XIIa, as the solid phase capture antibody. The assay for XIIaA used a conjugate based on a polyclonal antibody against the entire XIIa molecule, whilst the assay for XIIaR incorporated a reagent to release otherwise unavailable XIIa and used a conjugate based on a monoclonal antibody against β-XIIa.Results Changes in plasma XIIaA concentration as a result of therapy were more evident than changes in XIIaR concentration. XIIaA showed a significant increase from 67.1 (49.0–84.4) pM to 97.8 (75.5–133.1) pM [median and 25 and 75% percentiles] in the 30–90 min sample (P < 0.001), returning to pre-intervention levels 61.5 (47.5–81.0) pM by day 4. In contrast, no significant change in XIIaR concentration was observed following thrombolytic therapy with TNK-tpa.Conclusion In patients admitted with STEMI, thrombolytic therapy with TNK-tpa resulted in a significant short-lasting increase in specific types of XIIa (namely XIIaA), whereas other types of XIIa (XIIaR) were largely unaffected by this intervention.     

Surgical aspects of congestive heart failure

Despite tremendous advances in the medical management of congestive heart failure the gold standard for the treatment of end stage congestive heart failure remains cardiac transplantation. The acknowledged critical limitation of sufficient suitable organ donors has resulted in the refinement and development of novel surgical alternatives for the treatment of congestive heart failure. These approaches include the extension of current conventional cardiac operations such as mitral valve repair to the failing ventricle, surgically reconstructing the size and shape of the failing left ventricle in order to optimize geometry and render it a more efficient pump, and partial or complete replacement of the ventricle with a mechanical device. The continued evolution of such therapies is likely to one day have a significant epidemiologic impact on patients suffering from end stage heart failure.     

Characterization of cerebral tissue by MRI map ISODATA in embolic stroke in rat

ISODATA using MRI parameter-weighted images has been previously employed to characterize ischemic cell damage after stroke in rats. In an effort to increase the objectivity and to further automate the ISODATA, MRI parameter maps were now employed. Male Wistar rats were subjected to embolic stroke and received treatment via a femoral vein at 4 h post-stroke. The control rats received saline and were sacrificed at 6, 24 and 48 h after stroke, respectively. Treated rats received rtPA alone or were treated with a combination of rtPA and an antibody, 7E3 F(ab′)₂, against the glycoprotein receptor that binds the platelet to fibrin. These rats were sacrificed at 24, or 48, h post-stroke. T₁, T₂ and diffusion maps were employed for map ISODATA analysis. H&E histological analysis of coronal sections of tissue was performed and compared with map ISODATA from the corresponding sections. ISODATA signatures were highly correlated (R ∼ 0.80, P < 0.0001) with the ischemic cell damage analyzed at 6, 24 and 48 h post-stroke. At 24 and 48 h after stroke, ISODATA lesion sizes were highly correlated (R > 0.97, P < 0.001) with lesion sizes measured histologically. The combination treatment of rtPA and 7E3 F(ab′)₂ reduced both infarction size (P < 0.002) and average signature (P < 0.03) at 48 h after stroke, compared to saline-treated animals. No significant difference was found between saline and rtPA-alone-treated rats. The map ISODATA successfully provides objective and automated quantitation of the ischemic damage in both size and severity in an embolic stroke model of rat with and without a therapeutic intervention.     

An in vitro model of traumatic brain injury utilising two-dimensional stretch of organotypic hippocampal slice cultures

Traumatic brain injury (TBI) is caused by rapid deformation of the brain, resulting in a cascade of pathological events and ultimately neurodegeneration. Understanding how the biomechanics of brain deformation leads to tissue damage remains a considerable challenge. We have developed an in vitro model of TBI utilising organotypic hippocampal slice cultures on deformable silicone membranes, and an injury device, which generates tissue deformation through stretching the silicone substrate. Our injury device controls the biomechanical parameters of the stretch via feedback control, resulting in a reproducible and equi-biaxial deformation stimulus. Organotypic cultures remain well adhered to the membrane during deformation, so that tissue strain is 93 and 86% of the membrane strain in the x- and y-axis, respectively. Cell damage following injury is positively correlated with strain. In conclusion, we have developed a unique in vitro model to study the effects of mechanical stimuli within a complex cellular environment that mimics the in vivo environment. We believe this model could be a powerful tool to study the acute phases of TBI and the induced cell degeneration could provide a good platform for the development of potential therapeutic approaches and may be a useful in vitro alternative to animal models of TBI.     

The effects of anesthesia and muscle paralysis on the respiratory system

Background Oxygenation is impaired in almost all subjects during anesthesia, and hypoxemia for shorter or longer periods is a common finding. Moreover, postoperative lung complications occur in 3–10% after elective abdominal surgery and more in emergency operations.Discussion Rapid collapse of alveoli on induction of anesthesia and more widespread closure of airways seem to explain the oxygenation impairment and may also contribute to postoperative pulmonary infection. Causative mechanisms to atelectasis and airway closure seem to be loss of respiratory muscle tone and gas resorption.Conclusion Avoiding high inspired oxygen fractions during both induction and maintenance of anesthesia prevents or reduces atelectasis, while intermittent vital capacity maneuvers recruit atelectatic lung regions.     

On the Closing Sounds of a Mechanical Heart Valve

In the 1994 Replacement Heart Valve Guidance of the U.S. Food and Drug Administration (FDA), in-vitro testing is required to evaluate the potential for cavitation damage of a mechanical heart valve (MHV). To fulfill this requirement, the stroboscopic high-speed imaging method is commonly used to visualize cavitation bubbles at the instant of valve closure. The procedure is expensive; it is also limited because not every cavitation event is detected, thus leaving the possibility of missing the whole cavitation process. As an alternative, some researchers have suggested an acoustic cavitation-detection method, based on the observation that cavitation noise has a broadband spectrum. In practice, however, it is difficult to differentiate between cavitation noise and the valve closing sound, which may also contain high-frequency components. In the present study, the frequency characteristics of the closing sound in air of a Björk-Shiley Convexo-Concave (BSCC) valve are investigated. The occluder closing speed is used as a control parameter, which is measured via a laser sweeping technique. It is found that for the BSCC valve tested, the distribution of the sound energy over its frequency domain changes at different valve closing speeds, but the cut-off frequency remains unchanged at 123.32± 6.12 kHz. The resonant frequencies of the occluder are also identified from the valve closing sound.