Effects of superimposed pressure oscillations on a chronic sensitized airways mouse model.

The hyperconstriction of airway smooth muscle (ASM) is the main driving mechanism during an asthmatic attack. The airway lumen is reduced, resistance to airflow increases, and normal breathing becomes more difficult. The tissue contraction can be temporarily relieved by using bronchodilator drugs, which induce relaxation of the constricted airways. In vitro studies indicate that relaxation of isolated, precontracted ASM is induced by mechanical oscillations in healthy subjects but not in asthmatic subjects. Further, short-term acute asthmatic subjects respond to superimposed pressure oscillations (SIPO) generated in the range of 5-15 Hz with ~50% relaxation of preconstricted sensitized airways. Mechanical oscillations, and specifically SIPO, are not widely characterized in asthmatic models. The objective of this in vivo study is to determine the effects of a range of oscillation patterns similar to our previous acute study differing from normal breathing. Both healthy and sensitized mice were observed, with their responses to SIPO treatments measured during induced bronchoconstriction resulting from acetylcholine (Ach) challenge. SIPO-generated results were compared with data from treatments using the bronchorelaxant isoproterenol (ISO). The study shows that SIPO in the range of 5-20 Hz induces relaxation in chronic sensitized airways, with significant improvements in respiratory parameters at SIPO values near 1.7 cmH2O irrespective of the frequency of generation.

Superimposed pressure oscillations: An alternative to treat airway hyperresponsiveness in an acute sensitized airways mouse model.

The main driving mechanism during an asthma attack is the hyper-constrictions of airway smooth muscle (ASM), which reduces the airway lumen and makes normal breathing difficult. In spite of some noticeable side effects, bronchodilator drugs such as salbutamol are used to alleviate these symptoms by inducing temporary relaxation of the contracted ASM. In vitro studies have shown that mechanical oscillation can induce relaxation in isolated contracted ASM obtained from healthy subjects but not from asthmatics. To date, little is known about in vivo ASM behaviours, in particular in asthmatic subjects. This in vivo study aims at determining the effect of various superimposed pressure oscillation (SIPO) patterns (different to those occurring during normal breathing) on sensitized airways during an ACh challenge (mimicking an asthmatic attack) and comparing it with the effect of a widely studied broncho-relaxant drug, Isoproterenol (ISO). The study shows that superimposed pressure oscillation in the range of 5-15Hz induces approximately 50% relaxation on pre-constricted sensitized airways in vivo; however, this behaviour was not observed at 20Hz. Our finding suggests that mechanical oscillation, particularly SIPO, may act as a bronchodilator and achieve ASM relaxation.

Brachial artery waveforms for automatic blood pressure measurement.

Theoretically the auscultatory method using Korotkoff sounds is more related to the maximum artery closure status, while the oscillometric method is more related to the overall artery closure status under the cuff. Therefore, the latter is less accurate than the former. This work introduces a new method, which is more accurate than the oscillometric method and suitable for automatic devices. To monitor the maximum artery closure status, a piezoelectric film sensor is attached to the skin just above the brachial artery and under the central section of the cuff where maximum cuff pressure is transferred to the arm. Using the waveform features obtained by this sensor, measurement errors of 0.7±2.5 and 1.27±4.53 mmHg were obtained for the systolic and diastolic pressure, respectively. These reflect small deviations from auscultatory clinical data.

Effect of tissue mechanical properties on cuff-based blood pressure measurements.

This paper presents a 3D finite element upper arm model, validated by experiments as well as clinical data, used to study the error introduced in blood pressure measurements due to variability of arm tissue mechanical properties. The model consists of three separate cylindrical parts: soft tissue, bone and brachial artery. The artery volume changes under the cuff are used to represent the cuff pressure oscillations for analyzing blood pressure measurements. These oscillation trends are identical to observed clinical data. Also an upper arm simulator is designed and built for model validation. The model shows that the variation of soft tissue compressibility introduces an error up to 5% in blood pressure measurements. It is also revealed that the variation of the brachial artery and arm tissue stiffness has an insignificant effect on oscillometric blood pressure measurement method.

Fading memory model for airway smooth muscle dynamic response.

This work presents the application of a fading memory model to describe the behavior of contracted airway smooth muscle (ASM) for two biophysical cases: finite duration length steps and longitudinal sinusoidal oscillations. The model parameters were initially determined from literature data on transient step length change response and subsequently the model was applied to the two cases. Results were compared with previously published experimental data on ASM oscillations. The model confirms a trend observed in the experimental data which shows that: (i) the value of tissue length change is the most important factor to determine the degree of cross-bridge detachment and (ii) a strong correlation exists between increasing frequency and declining stiffness until a certain frequency (~25 Hz) beyond which frequency dependence is negligible. Although the model was not intended to simulate biophysical events individually, the data could be explained by cross-bridge cycling rates. As the frequency increases, cross-bridge reattachment becomes less likely, until no further cross-bridge attachment is possible.

Logarithmic superposition of force response with rapid length changes in relaxed porcine airway smooth muscle.

We present a systematic quantitative analysis of power-law force relaxation and investigate logarithmic superposition of force response in relaxed porcine airway smooth muscle (ASM) strips in vitro. The term logarithmic superposition describes linear superposition on a logarithmic scale, which is equivalent to multiplication on a linear scale. Additionally, we examine whether the dynamic response of contracted and relaxed muscles is dominated by cross-bridge cycling or passive dynamics. The study shows the following main findings. For relaxed ASM, the force response to length steps of varying amplitude (0.25-4% of reference length, both lengthening and shortening) are well-fitted with power-law functions over several decades of time (10⁻² to 10³ s), and the force response after consecutive length changes is more accurately fitted assuming logarithmic superposition rather than linear superposition. Furthermore, for sinusoidal length oscillations in contracted and relaxed muscles, increasing the oscillation amplitude induces greater hysteresivity and asymmetry of force-length relationships, whereas increasing the frequency dampens hysteresivity but increases asymmetry. We conclude that logarithmic superposition is an important feature of relaxed ASM, which may facilitate a more accurate prediction of force responses in the continuous dynamic environment of the respiratory system. In addition, the single power-function response to length changes shows that the dynamics of cross-bridge cycling can be ignored in relaxed muscle. The similarity in response between relaxed and contracted states implies that the investigated passive dynamics play an important role in both states and should be taken into account.

Non-invasive model-based estimation of aortic pulse pressure using suprasystolic brachial pressure waveforms.

Elevated central arterial (aortic) blood pressure is related to increased risk of cardiovascular disease. Methods of non-invasively estimating this pressure would therefore be helpful in clinical practice. To achieve this goal, a physics-based model is derived to correlate the arterial pressure under a suprasystolic upper-arm cuff to the aortic pressure. The model assumptions are particularly applicable to the measurement method and result in a time-domain relation with two parameters, namely, the wave propagation transit time and the reflection coefficient at the cuff. Central pressures estimated by the model were derived from completely automatic, non-invasive measurement of brachial blood pressure and suprasystolic waveform and were compared to simultaneous invasive catheter measurements in 16 subjects. Systolic blood pressure agreement, mean (standard deviation) of difference was -1 (7)mmHg. Diastolic blood pressure agreement was 4 (4)mmHg. Correlation between estimated and actual central waveforms was greater than 90%. Individualization of model parameters did not significantly improve systolic and diastolic pressure agreement, but increased waveform correlation. Further research is necessary to confirm that more accurate brachial pressure measurement improves central pressure estimation.

Understanding the use of continuous oscillating positive airway pressure (bubble CPAP) to treat neonatal respiratory disease: an engineering approach.

A continuous oscillatory positive airway pressure with pressure oscillations incidental to the mean airway pressure (bubble CPAP) is defined as a modified form of traditional continuous positive airway pressure (CPAP) delivery where pressure oscillations in addition to CPAP are administered to neonates with lung diseases. The mechanical effect of the pressure oscillations on lung performance is investigated by formulating mathematical models of a typical bubble CPAP device and a simple representation of a neonatal respiratory system. Preliminary results of the respiratory system's mechanical response suggest that bubble CPAP may improve lung performance by minimizing the respiratory system impedance and that the resonant frequency of the respiratory system may be a controlling factor. Additional steps in terms of clinical trials and a more complex respiratory system model are required to gain a deeper insight into the mechanical receptiveness of the respiratory system to pressure oscillations. However, the current results are promising in that they offer a deeper insight into the trends of variations that can be expected in future extended models as well as the model philosophies that need to be adopted to produce results that are compatible with experimental verification.

Smooth muscle stiffness variation due to external longitudinal oscillations.

This research focuses on an in vitro investigation of the stiffness changes of contracted airway smooth muscles (ASM) subjected to external longitudinal oscillations. ASM tissues were dissected from excised pig tracheas and stimulated by a chemical stimulus (acetylcholine, 10(-3) M) to produce maximum contractions. The tissues were then systematically excited with external oscillations. Various frequencies, amplitudes and durations were used in the experiments to determine stiffness changes in response to these variations. Force changes were recorded to reflect the muscle stiffness changes. Two stiffness definitions were used to quantify the results, dynamic stiffness to reflect variations during oscillation and static stiffness to reflect the net effect of oscillation. Under isometric contractions, these two stiffnesses were determined before, during and after oscillations. Incorporating an empirical stiffness equation, a two-dimensional finite element model (FEM) was developed to generalize the tissue responses to oscillation. The main outcomes from this work are: the dynamic stiffness has the tendency to decrease as the frequency and/or amplitude of external oscillation increases; the static stiffness has the tendency of decreasing with an increase in the frequency and/or amplitude of excitation until it reaches almost a constant value for frequencies at and above 25 Hz. The difference in the behavior of the dynamic and static stiffness changes may be attributed to the effect of elasticity and mass inertia that are involved in the dynamic motion. The findings of this research are in agreement with the hypothesis that oscillations exert a direct action on the contractile processes by causing an increased rate of actin-myosin detachments.

Obstruction identification in branching compliant tubes with application to airway passages.

A feasibility study for occlusion identification in a branched tube-like structure using the frequency spectrum of the acoustic input impedance determined at the main entrance to the network is presented. The frequency spectra for one- and two-generation models are generated to study the effect of an occlusion in one of the branches on the spectra with an application to the trachea and the first two generations of the airways. The result demonstrates that the input impedance resonant frequencies can map the location, severity and degree of an obstruction in any of the considered branches.