Pressure-diameter Behavior Research Articles

The passive biomechanics of human pelvic collecting lymphatic vessels.

The lymphatic system has a major significance in the metastatic pathways in women’s cancers. Lymphatic pumping depends on both extrinsic and intrinsic mechanisms, and the mechanical behavior of lymphatic vessels regulates the function of the system. However, data on the mechanical properties and function of human lymphatics are lacking. Our aim is to characterize, for the first time, the passive biomechanical behavior of human collecting lymphatic vessels removed at pelvic lymph node dissection during primary debulking surgeries for epithelial ovarian cancer. Isolated vessels were cannulated and then pressurized at varying levels of applied axial stretch in a calcium-free Krebs buffer. Pressurized vessels were then imaged using multi-photon microscopy for collagen-elastin structural composition and fiber orientation. Both pressure-diameter and force-elongation responses were highly nonlinear, and axial stretching of the vessel served to decrease diameter at constant pressure. Pressure-diameter behavior for the human vessels is very similar to data from rat mesenteric vessels, though the human vessels were approximately 10× larger than those from rats. Multiphoton microscopy revealed the vessels to be composed of an inner layer of elastin with an outer layer of aligned collagen fibers. This is the first study that successfully described the passive biomechanical response and composition of human lymphatic vessels in patients with ovarian cancer. Future work should expand on this knowledge base with investigations of vessels from other anatomical locations, contractile behavior, and the implications on metastatic cell transport.

Dysfunction in elastic fiber formation in fibulin-5 null mice abrogates the evolution in mechanical response of carotid arteries during maturation

Elastin fragmentation is a common characteristic of vascular diseases, such as abdominal aortic aneurysms, peripheral arterial disease, and aortic dissection. Examining growth and remodeling in the presence of dysfunctional elastic fibers provides insight into the adaptive or maladaptive changes that tissues undergo in compensating for structural deficiencies. This study used the maturation of fibulin-5 knockout (KO) and wild-type mice to study the effects of fragmented elastic fibers on the growth and remodeling of carotid arteries. The microstructural content and organization and the biaxial mechanical behavior of common carotid arteries were measured, and parameter estimation performed from KO and WT mice aged 3, 4, 8, and 13 wk. Gross measurements and biaxial tests revealed significant differences in pressure-diameter behavior, in vivo axial stretch, opening angle, compliance, and wall stresses during maturation of wild-type arteries, but little change in these values in KO mice. Multiphoton microscopy used to image collagen fibers across the vessel wall in pressurized and stretched arteries suggests that there is little variation in fiber angles between different ages. Parameter estimation revealed significant differences in material parameters between genotypes and age groups. This study suggests that neonatal formation and cross-linking of functional elastic fibers, followed by increases in artery size due to growth with little remodeling of the elastic fibers, endow arteries with large distensibility and contribute to the evolution of mechanical behavior of arteries during maturation. Dysfunction in neonatal formation of elastic fibers abrogates many of the changes in mechanical response that take place during the maturation.

Impact of Residual Stretch and Remodeling on Collagen Engagement in Healthy and Pulmonary Hypertensive Calf Pulmonary Arteries at Physiological Pressures

Understanding the mechanical behavior of proximal pulmonary arteries (PAs) is crucial to evaluating pulmonary vascular function and right ventricular afterload. Early and current efforts focus on these arteries' histological changes, in vivo pressure-diameter behavior and mechanical properties under in vitro mechanical testing. However, the in vivo stretch and stress states remain poorly characterized. To further understand the mechanical behavior of the proximal PAs under physiological conditions, this study computed the residual stretch and the in vivo circumferential stretch state in the main pulmonary arteries in both control and hypertensive calves by using in vitro and in vivo artery geometry data, and modeled the impact of residual stretch and arterial remodeling on the in vivo circumferential stretch distribution and collagen engagement in the main pulmonary artery. We found that the in vivo circumferential stretch distribution in both groups was nonuniform across the vessel wall with the largest stretch at the outer wall, suggesting that collagen at the outer wall would engage first. It was also found that the circumferential stretch was more uniform in the hypertensive group, partially due to arterial remodeling that occurred during their hypoxic treatment, and that their onset of collagen engagement occurred at a higher pressure. It is concluded that the residual stretch and arterial remodeling have strong impact on the in vivo stretch state and the collagen engagement and thus the mechanical behavior of the main pulmonary artery in calves.

Effect of a Phosphodiesterase 5 Inhibitor on Pulmonary and Cerebral Arteries of Newborn Piglets with Chronic Hypoxia-Induced Pulmonary Hypertension

Background: The use of phosphodiesterase 5 (PDE5) inhibitors to treat newborns with pulmonary hypertension is increasing. The effect of PDE5 inhibitors on the neonatal cerebral circulation remains unknown. The neonatal piglet model of chronic hypoxia-induced pulmonary hypertension allows the study of the effects of PDE5 inhibitors on both the pulmonary and cerebral circulations. Objectives: To determine whether the PDE5 inhibitor, zaprinast, causes dilation in pulmonary and middle cerebral arteries (MCA) of normoxic newborn piglets and those with chronic hypoxia-induced pulmonary hypertension, and to evaluate whether zaprinast alters responses to increased pressure (autoregulatory ability) of the MCA. Methods: Two-day-old piglets were raised in normoxia or hypoxia for 3 or 10 days. Pulmonary arteries and MCA were isolated and pressurized, after which changes in diameter to zaprinast were measured. MCA pressure-diameter relationships were determined. Results: Dilation to zaprinast was similar in pulmonary arteries from normoxic and hypoxic piglets. Zaprinast dilated MCA from all groups but the response was diminished in MCA from piglets raised in hypoxia for 10 days. MCA pressure-diameter relationships (autoregulation) did not differ between the groups. Conclusions: Pulmonary artery dilation to zaprinast supports the use of PDE5 inhibitors to treat pulmonary hypertension in neonates. PDE5 inhibitors function as MCA dilators but do not impair the pressure-diameter behavior of the cerebral circulation of either normoxic newborn piglets or those with chronic hypoxia-induced pulmonary hypertension. These findings suggest that cerebral autoregulation is likely to be intact with acute PDE5 inhibitor treatment in infants with pulmonary hypertension in conditions associated with chronic hypoxia.

Improvement of Young modulus estimation by ultrasound using static pressure steps

In this work the radial displacement of the arterial wall is measured using a cross correlation algorithm. An elastic model for static pressure conditions is developed, fit to the boundary conditions of the physical problem. Measuring the wall displacements as pressure changes the biomechanical behavior of the arterial wall can be characterized. Validation measurements were performed in a calibrated latex tube. The obtained experimental results are in good agreement with the theoretical model. Human arteries were also characterized. The typical non linear pressure-diameter behavior due to the presence of elastine and collagen was observed. Human arteries with atheroma plaques were also studied presenting a different Young modulus than the healthy ones. From these results we conclude that this method could be used in the characterization of arterial mechanical alterations and/or in the post-implant biomechanical evaluation of vascular grafts.

Pressure‐diameter behavior of airways measured from tantalum bronchograms in isolated mouse lungs

In a previous study, conscious mice in response to methacholine aerosol reached a limit in airway constriction that occurred near zero airway elastic recoil, based on an analysis using elastic and active properties of large dog airways (J. Appl. Physiol. 105: 933‐941, 2008). We wondered whether mice have airway elastic properties similar to dogs. Balb/c mice (n = 5, 23‐27 g) were anesthetized and tantalum dust (5 micron) was insufflated via a 22‐G catheter into the lungs using a 0.2 ml air injection to produce a well‐defined bronchogram. Postmortem, the chest was opened and the lungs were inflated to 25 cmH2O transpulmonary pressure (Ptp) then deflated in steps to 10, 5, 0, ‐5 and ‐10 cmH2O. Tantalum bronchograms were taken at each Ptp. Airway diameters (8‐10) located between 1 and 8 airway generations were measured from the bronchograms of each mouse. Airway diameter decreased from a maximum (Dmax) at 25 cmH2O Ptp to 87, 79, 60, 50 and 47 %Dmax at 10, 5, 0, ‐5 and ‐10 cmH2O Ptp, respectively. The pressure‐diameter (PD) behavior was similar for both large (Dmax of 0.75 ± 0.11 (SD) mm) and small (Dmax of 0.32 ± 0.026 mm) airways. The measured PD behavior of mice was similar to that reported for dog airways (J. Appl. Physiol. 44: 859‐868, 1978). Supported by NIH grant HL 36597.

Maturation of interdependence between extra-alveolar arteries and lung parenchyma in piglets.

Mechanical interdependence between intrapulmonary structures and parenchyma has not been studied previously in immature postnatal lungs. To study these interactions, lung elastic moduli were measured by pressure-volume and punch indentation studies in lobes excised from 3-day-old (n = 6), 1-month-old (n = 6), and 3-month-old (n = 7) piglets. After extra-alveolar arteries were filled with a radiopaque fluid silicone compound, transpulmonary pressure and arterial pressure were varied independently as the lobar vein was occluded. Arterial diameters and lengths were measured from radiographs. Behavior of 3-month-old lungs was consistent with previous studies of adult lungs, but results were unique in 3-day-old lungs. That is, during stepwise deflation of the immature lungs 1) intravascular pressures fell when arteries were occluded experimentally, 2) arteries increased their diameters when kept at a constant intravascular pressure, and 3) arterial lengths decreased by less than 3%. Behavior of 1-month-old lungs was intermediate. A previous continuum mechanics analysis of pressure-diameter behavior was modified to account for compression by alveolar pressure as vascular diameters increase. It was concluded that 1) radial and axial dimensions of extra-alveolar arteries are virtually independent of parenchymal expansion in newborn piglet lungs and 2) periarterial interstitial pressures increase as these lungs are inflated. Our interpretation of these findings is that a mechanical association of the arteries to the parenchyma occurs gradually with postnatal maturation.

Maximum expiratory flow-volume curves during short periods of microgravity

To elucidate the effect of normal gravitation on the shape of the maximum expiratory flow-volume (MEFV) curve, we studied nine normal subjects in a National Aeronautics and Space Administration microgravity research aircraft. They performed multiple MEFV maneuvers at 0, 1, and approximately 2 G. The MEFV curves for each subject were filtered, aligned at residual volume, and ensemble averaged to produce an average MEFV curve for each state, allowing differences to be studied. Most subjects showed a decrease in the forced vital capacity at 0 G, which we attribute to an increased intrathoracic blood volume. In most of these subjects, the mean lung volume associated with a given flow was lower at 0 G over about the upper half of the vital capacity. This is similar to the change previously reported during headout immersion and is consistent with the known effect of engorgement of the lung with blood on elastic recoil. There were also consistent but highly individual changes in the position and magnitude of detailed features of the curve, the individual patterns being similar to those previously reported on transition from the erect to the supine position. This supports the idea that the location and motion of choke points that determine the detailed individual configuration of MEFV curves can be significantly influenced by gravitational forces, presumably via the effects of change in longitudinal tension on local airway pressure-diameter behavior and thus wave speed.

Small airway pressure-diameter relationships during nonhomogeneous lung lobe inflation.

The pressure-diameter behavior of airways within a collaterally ventilating segment of lung was evaluated radiographically in 12 excised dog lung lobes. The results were compared with the pressure-diameter behavior of airways in a lung region adjacent to the collaterally ventilating segment. Airways in each lung region were dusted with powdered tantalum, and airway diameters were measured during homogeneous and nonhomogeneous lobe inflation. Intrasegmental and extrasegmental airways behaved similarly during homogeneous lobe inflation; airway diameter increased as alveolar pressure increased. The lobe was inflated nonhomogeneously by raising pressure in the collaterally ventilating segment (Ps) while maintaining pressure at the lobar bronchus (Pao) constant at 5, 10, or 15 cmH2O. Increasing Ps at constant Pao reciprocally affected intrasegmental and extrasegmental airways. When Pao was low, intrasegmental airways were expanded, and extrasegmental airways were compressed when Ps was raised. When Pao was high, airway diameter was unaffected by increasing Ps presumably because the airways were already maximally expanded. A comparison of diameters during homogenous and nonhomogenous lobe inflation suggests a very small interdependence effect from the parenchyma surrounding the collaterally ventilating segment. These results demonstrate the combined effects of parenchymal properties and airway pressure-diameter relationships in determining the effect of local lung distortion on airway function.

Effects of posture on flow-volume curve configuration in normal humans.

Tien et al. (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 46: 565-570, 1979) found reproducible details in the configuration of averaged maximal expiratory flow-volume curves and suggested that these details may correspond to sudden relocations of airway choke points. The occurrence of choke points depends on factors affecting local airway pressure-diameter behavior. We postulated that changes in posture as they affect the distribution of lung recoil on airways might change the locations of choke points and thereby alter flow-volume configuration. Twenty normal adults performed five flow-volume curves in each of four postures (standing, supine, right, and left lateral recumbent). Volume was measured with a Krogh spirometer and airflow with a Fleisch No. 4 pneumotachometer. Curves were digitally filtered and plotted relative to upright total lung capacity. Five curves in each posture were averaged at increments of 0.1 l/s of flow and average volumes at given flows were compared using the Student's t test. Significant differences (P less than 0.01) in mean volumes at given flows occurred in all subjects from standing to supine and/or right to left lateral postures. Large changes in configuration were apparent in one of the two postural pairs in eight subjects. We conclude that changes in posture result in significant changes in flow-volume configuration in most normal adults. These findings are consistent with the wave-speed theory of flow limitation and suggest that small changes in local airway stresses can significantly alter the location and motion of airway choke points during forced expiration.

Effect of parenchyma and length changes on vessel pressure-diameter behavior in pig lungs.

At several transpulmonary pressures (Ptp), the pressure-diameter (PD) behavior of the largest intraparenchymal arterial segment in the isolated pig lung was compared with the behavior of the segment after its excision from the parenchyma and its extension to lengths equivalent to those in the intact state. For physiological changes in length, as may occur with lung inflation during Ptp changes from 4 to 25 cmH2O, excised-vessel diameters did not change significantly at a constant transmural pressure. The excised-vessel PD behavior was not significantly different from the intact-vessel PD behavior at a Ptp of 4 cmH2O. At any constant arterial pressure, intact-vessel diameters became larger as Ptp increased. Estimates of the perivascular pressure (Px) obtained by directly comparing intact-vessel and excised-vessel PD curves were as follows: 1) Px was equal to pleural pressure at a Ptp approximating the functional residual capacity; 2) Px decreased almost linearly as Ptp increased; and 3) Px decreased with a fall in arterial pressure. These results are consistent with direct measurements of the perivascular interstitial fluid pressure.

A continuum mechanics analysis of pulmonary vascular interdependence in isolated dog lobes

The pressure-diameter (PD) behavior of intact pulmonary vessels was measured roentgenographically at several fixed deflation transpulmonary pressures (Ptp). At any constant vascular pressure (Pv), the intact-vessel diameter was larger for higher Ptp. The behavior of the parenchyma was described by a nonlinear analysis. An excised-vessel PD behavior was computed which was consistent with both nonlinear parenchymal behavior and measured intact-vessel PD behavior. Estimates of Px', the difference between the perivascular pressure and the pleural pressure, as a function of Ptp and Pv were obtained. For physiological values of Pv, mean values of Px' for arteries were -1 cmH2O at Ptp of 4 cmH20 and decreased almost linearly to -15 cmH20 at Ptp of 25 cmH2O. Veins showed a similar behavior, but Px' was more positive. Increasing Pv raised Px' and decreasing Pv lowered Px' at all values of Ptp. These results indicate that the interdependence effect is small at functional residual capacity, increases with lung inflation, and is greater for arteries than veins.

Static mechanical properties of bronchi in normal excised human lungs.

Bronchographic studies were performed on 22 normal human lungs at transpulmonary pressures between 20 and 0 cmH2O. Pressure-diameter behavior of 322 bronchi was evaluated. In younger (less than 40 yr) subjects, the airways of males showed greater recoil than those of females. No difference between sexes was seen in older (greater than 40 yr) subjects. Bronchi less than 2.1 mm diam had a significant decrease in recoil with increasing age in males but not in females. Small bronchi had greater recoil than large bronchi in both sexes in the younger group but not in the older group. The younger group had evidence of anisotropic behavior of the bronchi not seen in the older group. The percentage decrease in lung volume for a given decrease in transpulmonary pressure was less in the older than in the younger subjects in both sexes. Measurements of the cube root of lung volume, bronchial length, and the position of markers attached to the pleura indicated that the lungs deflated in an overall, isotropic manner down to a pressure of 3 cmH2O.

Effect of parenchymal shear modulus and lung volume on bronchial pressure-diameter behavior.

A method that interrelates lung pressure-volume behavior, bronchial pressure-diameter behavior, and parenchymal shear modulus is presented. The method was used to predict changes in intraparenchymal bronchial diameter that occurred when lobe pressure-volume behavior and parenchymal shear modulus were markedly changed by inducing air trapping in isolated dog lobes. Predictions agreed with measurements, thereby supporting the general method. Measured values for the shear modulus were approximately 0.7 times the transpulmonary pressure for the control state. Estimated values for the peribronchial pressure difference from pleural pressure during a deflation pressure-volume maneuver for transpulmonary pressures below 12 cmH2O were small, approximately +/- 1 cmH2O, its sign being positive or negative, depending on whether the bronchus was dilated or contricted.