Role of smooth muscle activation in the static and dynamic mechanical characterization of human aortas

Experimental data and a suitable material model for human aortas with smooth muscle activation are not available in the literature despite the need for developing advanced grafts; the present study closes this gap. Mechanical characterization of human descending thoracic aortas was performed with and without vascular smooth muscle (VSM) activation. Specimens were taken from 13 heart-beating donors. The aortic segments were cooled in Belzer UW solution during transport and tested within a few hours after explantation. VSM activation was achieved through the use of potassium depolarization and noradrenaline as vasoactive agents. In addition to isometric activation experiments, the quasistatic passive and active stress–strain curves were obtained for circumferential and longitudinal strips of the aortic material. This characterization made it possible to create an original mechanical model of the active aortic material that accurately fits the experimental data. The dynamic mechanical characterization was executed using cyclic strain at different frequencies of physiological interest. An initial prestretch, which corresponded to the physiological conditions, was applied before cyclic loading. Dynamic tests made it possible to identify the differences in the viscoelastic behavior of the passive and active tissue. This work illustrates the importance of VSM activation for the static and dynamic mechanical response of human aortas. Most importantly, this study provides material data and a material model for the development of a future generation of active aortic grafts that mimic natural behavior and help regulate blood pressure.

The rupture of aortic aneurysms causes around 10,000 deaths each year in the United States (1). Surgical repair of aortic aneurysms and aortic dissections absorb significant healthcare resources (2). Prosthetic tubes made of polyester (Dacron) or polytetrafluoroethylene are often used for the surgical repair of large arteries in aneurysms or acute dissection. Unfortunately, these grafts are so stiff to diameter expansion (3) that they can cause cardiovascular and perfusion problems because they fail to reduce the highly pulsatile nature of the blood flow exiting the heart. This is the reason for an increasing interest in the development of a new generation of grafts (4) in innovative biomaterials or in tissue engineering that mimic the dynamic behavior of the aorta, which is achieved through the correct adjustment of mechanical properties and the introduction of a layered design. Arteries respond to vasoactive chemical stimuli by varying their mechanical properties and diameter because of vascular smooth muscle (VSM) activation; this helps in regulating blood pressure (5). We envision a future generation of aortic grafts based on tissue engineering that mechanically respond to vasoconstrictors to maintain this function. To achieve this result, it is first necessary to investigate the relationship between VSM activation and the mechanical properties of the aorta and to develop a suitable model of the active mechanical response for the graft design. Since the VSM is mainly located in the tunica media (some cells can infiltrate the intima and adventitia with increasing age), the activation strain can be attributed to this aortic layer. Experimental data and a suitable material model for human aortas with smooth muscle activation are not available in the literature despite the need for the development of advanced grafts. This appears to be due to the difficulty of obtaining suitable human samples. In fact, VSM activation is only possible for a small number of hours after the explantation from a heart-beating donor (i.e., donor in intensive care unit with neurological determination of death) and when the tissue is kept refrigerated in organ preservation solution all the time before testing. The present study is important as it provides much-needed experimental data. These data made it possible to create a precise structure-based model of the active aortic tissue and to identify the corresponding material parameters.The passive (i.e., without VSM activation) quasistatic mechanical properties of the intact wall of the human aorta and its three individual layers have been extensively investigated experimentally. In particular, uniaxial extension tests were carried out on strips (cut in the circumferential and longitudinal directions) from the intact wall or separated layers (6–9), and biaxial tests on squares and cruciform samples of aortic tissue (10, 11) were conducted. The microstructure of the collagen and elastin fiber distributions in the three layers was also examined in detail using second-harmonic generation and two-photon excited fluorescence microscopy (9, 10, 12). Along with the progress of experiments, advanced structure-based material models have also been refined. It was assumed that a ground substance/elastin matrix is reinforced by collagen fibers. The orientations and dispersions of the collagen fiber identified from experiments were taken into account in the more advanced models (13–15). The passive dynamic material properties (also referred to as viscoelastic) of the human aortas, on the other hand, are much less studied, even if they are of great importance since the aorta is dynamically loaded by pulsating pressure under physiological conditions. The experiments were performed on a mock circulatory loop under physiological pulsatile pressure and flow (3, 16) and on strips of thoracic descending aortas (8, 17). Viscoelastic models have been developed (18, 19), but they can only partially describe the experimental results. Experimental data show that the aorta stiffens with increasing age (8, 9, 11), which favors hypertension (20).The active (i.e., with VSM activation), quasistatic mechanical characterization of arteries has been less studied than its passive counterpart. The number of studies on human samples is very limited (21, 22), and none have been found on large arteries. Vasoactive agents commonly used to induce VSM contraction are potassium depolarization (KCl) (23), noradrenaline (22), norepinephrine (21), and phenylephrine (24). By using different concentrations of agents, different degrees of activation can be achieved. In previous studies, two methodologies of activation experiments were carried out: 1) pressurization of arterial segments (21, 24–29) and 2) extension tests on arterial strips and rings (5, 22, 30–32). Experiments on strips and rings can be isometric, in which the sample is constantly stretched, and the increase in force from the passive to the active state is measured (5); these are the typical experiments that are carried out on a myograph (22). In isobaric experiments performed on arterial segments, the pressure and axial stretch are fixed; activation of the VSM leads to a reduction in diameter (5). Approximation formulas allow the change in diameter to be linked to the arterial stiffness. Another type of experiment can be performed to measure the force-displacement curve (then converted to stress/strain) in the case of VSM activation by following a similar procedure used for passive mechanical characterization (6–9). A comparison of the active and passive curves gives the mechanical characteristics of the VSM activation. Excluding refs. 5, 28, and 30, a literature review shows that activation was only measured in the circumferential direction. Indeed, the orientation of VSM cells in arteries has usually been believed to be almost circumferential; the present study shows that this is not the case with the descending thoracic aorta in humans. Mechanical models of the mechanical response of active arteries have been developed (5, 14, 33–39) but generally only consider activation in the circumferential direction. There are two exceptions: the model in ref. 5 introduces independent activation stresses in the circumferential and axial directions; another study (38) considers two helically arranged symmetric families of VSM without fiber dispersion.In the present study, the active and passive mechanical characterization of human descending thoracic aortas was performed on specimens from 13 heart-beating donors. The aortic segments were cooled in Belzer UW solution during transport and tested within a few hours after explantation. VSM activation was achieved through the use of KCl and noradrenaline as vasoactive agents. In addition to isometric activation experiments, the quasistatic passive and active stress–strain curves for circumferential and longitudinal strips of the aortic material were obtained. This characterization made it possible to build an original mechanical model of the active aortic material that exactly matched the experimental data. The dynamic mechanical characterization was also performed using cyclic strain at different frequencies of physiological interest. An initial prestretch, which corresponded to the physiological conditions, was applied before the cyclic loading. Dynamic tests allowed to identify the differences in the viscoelastic behavior of the passive and active tissue. The influence of age was also studied. The present study illustrates the importance of VSM activation for the static and dynamic mechanical response of human aortas. Most importantly, it provides material data for the development of a future generation of active aortic grafts that mimic the natural behavior.     

Effects on proliferation ability of vascular smooth muscle cells by static and/or dynamic cell culture: utility of pre-seeding technique for dynamic cell culture

OBJECTIVES: Conventional biomaterials are not viable, do not grow, and do not provide contractile effects in cardiac tissue. Foreign synthetic material may become thrombogenic or infected. The most recent cardiac constructs consist of biodegradable material which has the potential to solve these problems. However, dynamic three-dimensional cell culture is necessary because conventional culture is limited to construct tough biografts. METHODS: Vascular smooth muscle cells derived from rat aorta were seeded to poly-L-lactide-epsilon-capro-lactone copolymer in three groups; static culture group (static cell seeding + static cell culture), dynamic culture group (dynamic cell seeding + dynamic cell culture), and pre-seeding group [static cell seeding and culture for 1 week (pre-seeding) + dynamic cell culture]. The dynamic cell culture system used an original spinner flask. The pre-seeding technique used static cell seeding and culture before dynamic culture. The three groups were evaluated by cell proliferation and histologic studies. RESULTS: Vascular smooth muscle cells could be proliferated in/on the biodegradable materials. The pre-seeding group cells grew much more efficiently than the other groups. Very few cells were found in the biodegradable materials with the dynamic groups. However, there were many cells in the materials with the static culture group and pre-seeding group, especially the pre-seeding group. CONCLUSIONS: Dynamic culture is useful for constructing tough biografts by the pre-seeding technique.     

Reference values for dynamic and static pulmonary compliance in men

The aim of the present study was to determine new reference values and predictive variables for dynamic and static pulmonary compliance in men. The investigation was conducted as a prospective study in healthy, non-smoking men with normal pulmonary function parameters including spirometry, bodyplethysmography and CO diffusing capacity. The esophageal pressure method was used to measure dynamic compliance (Cdyn), specific dynamic compliance (Cdyn/ITGV), static compliance (Cstat) and specific static compliance (Cstat/ITGV). Lung recoil pressures were recorded at different levels of total lung capacity (TLC). A total of 208 men aged 20-69 years were included in the study. The mean values for the compliance parameters were: Cdyn: 2.91+/-1.08 L/kPa; Cdyn/ITGV: 0.71 +/- 0.30 kPa (-1); Cstat: 3.34 +/- 1.04 L/kPa; Cstat/ITGV: 0.82 +/- 0.31 kPa (-1). Cdyn, Cdyn/ITGV and Cstat/ITGV were significantly correlated with age and Cstat was related to height, but in multiple regression analyses the predictability for compliance parameters was very low. Lung recoil pressures at all TLC levels significantly decreased with ageing. In conclusion, we demonstrated that the contribution of anthropometric variables to the regression equations of pulmonary compliance was low. With ageing the static pressure-volume curve of the lung shifted to the left without substantial alteration of the slope.     

Diastolic time during static and dynamic exercise in myocardial infarction

To evaluate the difference in the response of DT in the early phase of static (sustained weight load) and dynamic (treadmill) exercise, the relation of DT and HR was studied by ear densitography in 11 patients with myocardial infarction. None of the patients had an ischemic electrocardiographic response during exercise. Despite an increase in HR and the pressure-HR product with both types of exercise, the pressure-HR product was significantly higher at three minutes of dynamic exercise, which was associated with a significant lengthening of left ventricular ejection time. Diastolic blood pressure rose significantly during static exercise, but it remained unchanged with dynamic exercise. Electromechanical systole and HR had a linear inverse relation at three minutes of exercise, and DT and HR had a nonlinear inverse relation (DT = e7.29-0.0156 x HR, and DT = e7.07-0.0142 x HR for static and dynamic exercises, respectively). A significant prolongation of QS2 with a consequent shortening of DT (p less than 0.05) was observed in dynamic exercise. In addition to a higher pressure-HR product, the disproportionate shortening of diastole in the early phase of dynamic exercise has a potential for initiating imbalance of myocardial oxygen supply and demand.     

Plasma renin activity during and after dynamic and static exercise.

The effect of dynamic and static exercise on plasma renin activity was investigated in three normal males. Near maximal supine exercise for 10 min on a bicycle ergometer caused a small increase in plasma renin activity during exertion with a much larger increase during recovery which reached a peak between 10-20 min. Supine exercise at half this level and static exercise (hand-grip) had no detectable effect on plasma renin activity.     

Cardiac autonomic modulation following high-intensity static muscle contractions

BACKGROUND: The purpose of this investigation was to examine cardiac autonomic modulation, as measured by wavelet analysis of heart rate variability, following a series of high-intensity static muscle contractions. METHODS: After 10 minutes of rest, electrocardiograms (ECGs) were collected in 17 participants (age, 24.5 +/- 1 yr) 2.5 minutes before (REST) and 10 minutes after a series of static contractions of the knee extensors. Participants performed contractions with the nondominant leg (knee fixed at 90 degrees) at either 70% or 85% (randomized order) of their maximal voluntary contraction (MVC) on two separate visits. The postexercise ECGs were further divided into four consecutive 2.5-minute segments (POST 1-POST 4) to evaluate the time course of any possible autonomic changes after exercise. Each 2.5-minute segment was evaluated for the standard deviation of normal RR intervals (SDNN) and the percentage of successive RR intervals that differed by more than 50 ms (pNN50). Frequency-domain indices were obtained via wavelet transformation giving coefficients that reflected high- and low-frequency fluctuations in heart period (HFw and LFw). RESULTS: SDNN was elevated during POST-1 and pNN50 was reduced during POST-3 and POST-4 (P < 0.05) compared to REST for both intensities. Furthermore, HFw and LFw were increased during POST-1 and reduced during POST-3 and POST-4 compared to REST for both intensities (P < 0.05). CONCLUSION: These data suggest that complex alterations cardiac autonomic modulation exist for at least 10 minutes following a series of high-intensity static contractions performed at either 70% or 85% of MVC.     

Parasite prevalence: a static measure of dynamic infections

The intensity of malaria transmission is often measured by looking at the fraction of individuals infected at a given point in time. However, malaria infections in individuals are dynamic, leading to uncertainty about whether a cross-sectional survey that represents a single snapshot in time is a useful representation of a temporally complex process. In this analysis, we examine the impact of parasite density fluctuations on the measurement of parasite prevalence. Our results show that parasite prevalence may be underestimated by 20% or more, depending on the sensitivity of parasite detection.     

Assessment of static and dynamic plantar data of patients with acromegaly

Pituitary - To determine both static and dynamic plantar data of acromegalic subjects while barefoot. Seventy acromegalic patients and 48 age-, sex-, weight- and height-matched healthy controls...     

Differential increase in natriuretic peptides in elite dynamic and static athletes.

The echocardiographic measures and plasma concentrations of either atrial natriuretic peptide (ANP) or brain natriuretic peptide (BNP) were compared in elite judo practitioners (static athletes), elite marathon runners (dynamic athletes) and healthy controls to investigate the relationship between the different types of left ventricular (LV) hypertrophy and plasma concentrations of natriuretic peptides in athletes. The LV mass and LV wall thickness of marathon runners and judo practitioners were significantly greater than those of controls. The LV end-diastolic dimension index was significantly larger in the marathon group, but smaller in the judo group. The left atrial dimension (LAD) index was significantly larger only in marathon runners. Plasma BNP concentrations were higher in both the judo and marathon groups than in controls, and positively correlated with LV mass as well as with deceleration time. Plasma ANP concentrations were significantly higher in marathon runners than in the controls and judo groups, and positively correlated with the LAD index, but negatively correlated with ejection fraction. Multivariate analyses showed that the type of athlete and LAD index were independent predictors of plasma BNP and ANP concentrations, respectively. Thus, there is an intimate link between plasma concentrations of natriuretic peptides and cardiac morphology in different types of athletes.     

PROMs in inflammatory arthritis: moving from static to dynamic

There are several advantages in using patient-reported outcome measures (PROMs) in standard clinical practice, particularly if a questionnaire is distributed to each patient at each visit as a standard in the infrastructure usual care. The patients, being the most knowledgeable persons concerning their pain and global estimate, do most of the work by completing a questionnaire. Completion of the questionnaire helps the patients prepare for their visit as well as improving doctor–patient communication. Recently, the role of PROMs has expanded from the static phase of capturing and measuring outcomes at a single point of time to a more dynamic role. This dynamic role is aiming at driving improvement not only in the quality of inflammatory arthritis care but also in the patients' reported experience. Therefore, in addition to its value in tailoring treatment targets adapted to the patient's needs, PROMs also have the potential of modifying the disease impact through improving the patients' adherence to therapy and allowing the patients to monitor the changes in their condition. Though more attention has been given to the use of PROMs in routine clinical care, little was published regarding what could be done with the plethora of data gained from PROMs and how dynamic it can be enhancing the “patient-centered care” approach and improving patients' experience. This article highlights the value of adopting PROMs for arthritic patients in standard clinical practice and its impact on long-term patients' management.     

Roles of static and dynamic domains in stability and catalysis of adenylate kinase

Protein dynamics, including conformational switching, are recognized to be crucial for the function of many systems. These motions are more challenging to study than simple static structures. Here, we present evidence suggesting that in the enzyme adenylate kinase large "hinge bending" motions closely related to catalysis are regulated by intrinsic properties of the moving domains and not by their hinges, by anchoring domains, or by remote allosteric-like regions. From a pair of highly homologous mesophilic and thermophilic adenylate kinases, we generated a series of chimeric enzymes using a previously undescribed method with synthetic genes. Subsequent analysis of the chimeras has revealed unexpected spatial separation of stability and activity control. Our results highlight specific contributions of dynamics to catalysis in adenylate kinase. Furthermore, the overall strategy and the specific mutagenesis method used in this study can be generally applied.     

Vitamin B6 status and static muscle function. 2 case reports

2 young adult females, identified as vitamin B6 deficient based on xanthurenic acid excretion levels following a loading dose of tryptophan, were tested twice during each of 3 menstrual cycles for static muscle strength and endurance of the handgrip muscles. During each of the last 2 cycles either a 25-mg dose of pyridoxine hydrochloride or a placebo were administered daily in the double-blind fashion. Measurement of 24-hour xanthurenic acid and 4-pyridoxic acid excretion levels indicated correction of the biochemical indicators of vitamin B6 deficiency. Results of the tests of static muscle strength and endurance indicated no substantial improvement following vitamin B6 supplementation.     

Analysis of rectal dynamic and static compliances in patients with irritable bowel syndrome

Aims Our aim was to investigate whether the dynamic and static compliances differ between patients with irritable bowel syndrome (IBS) and normal subjects. Materials and methods Fifty-five IBS patients (age range 20–65 years, mean age 39.0 years, 28 women and 27 men; 36 diarrhea-predominant IBS (IBS-D) patients and 19 constipation-predominant IBS (IBS-C) patients) with symptoms that fulfilled the Rome-II criteria and 21 healthy controls (age range 25–58 years, mean age 37.8 years; 11 women and ten men) were recruited. The anorectal functions, including dynamic compliance, were evaluated via barostat tests. A power exponential model was used for the evaluation of static compliance. Results There was no significant difference in dynamic compliance between the normal subjects and the IBS patients (10.3 ± 3.1 and 8.9 ± 2.9 mmHg, respectively, P > 0.05). However, even though no significant difference was detected in the overall shape of the curve (β; P > 0.05), there were significant differences in the κ and P _half between the normal subjects and the IBS patients (P < 0.05), respectively. When we compared the dynamic and static compliances between the IBS-C and IBS-D patients, there were no significant differences found (P > 0.05). Conclusions An exponential model provided good fit to the actual data, and there were significant differences in static compliance between the normal subjects and the IBS patients. This result can reveal the altered biomechanical properties of the gut wall in IBS patients.     

Learning effects, variation during office hours and reproducibility of static and dynamic spirometry

Static and dynamic spirometric tests were performed in 21 healthy subjects (21-61 years old, 8 smokers and 9 ex-smokers) on 3 different days within 2 weeks. The design of the study allowed separation of the influence of learning and diurnal changes between 09.00 and 17.00 h. In addition, the reproducibility of the tests and the effect of inhalation of 2.5 mg of terbutaline sulphate were studied. No learning effect was observed. There were slight, but statistically significant differences between morning, noon and afternoon measurements. Thus, the residual volume and flow in the early phase of forced expiration were highest in the afternoon, while maximal voluntary ventilation was lower at noon than in the afternoon or morning. The intraindividual variabilities (defined as standard deviation of difference between first and second measurement) of total lung capacity, vital capacity and forced expiratory volume in 1 s (FEV1) were about 3% of the predicted values. The ratio of intra- to interindividual variability was 0.2-0.3. The remaining tests showed higher variability and a higher intra- to interindividual variability ratio. Terbutaline inhalation caused a significant increase in most forced expiratory flow variables. A 10% increase in FEV1 corresponded to a 50-60% increase in endexpiratory flow. In spite of this, the endexpiratory flow and mean transit time were better discriminators of the effects of bronchodilation in normal subjects.