The effects of aneurysm on the biaxial mechanical behavior of human abdominal aorta

The biomechanical response of normal and pathologic human abdominal aortic tissue to uniaxial loading conditions is insufficient for the characterization of its three-dimensional (3D) mechanical behavior. Planar biaxial mechanical evaluation allows for 3D constitutive modeling of nearly incompressible tissues, as well as the investigation of the nature of mechanical anisotropy. In the current study, 26 abdominal aortic aneurysm (AAA) tissue samples and 8 age-matched (> 60 years of age) nonaneurysmal abdominal aortic (AA) tissue samples were obtained and tested using a tension-controlled biaxial testing protocol. Graphical response functions (Sun et al., 2003. J. Biomech. Eng. 125, 372-380) were used as a guide to describe the pseudo-elastic response of AA and AAA. Based on the observed pseudo-elastic response, a four-parameter exponential strain energy function developed by Vito (1990. J. Biomech. Eng. 112, 153-159) was used from which both an individual specimen and group material parameter sets were determined for both AA and AAA. Peak Green strain values in the circumferential (Ethetatheta,max) and longitudinal (ELL,max) directions under an equibiaxial tension of 120 N/m were also compared. The strain energy function fit all of the individual specimens well with an average R2 of 0.95 +/- 0.02 and 0.90 +/- 0.02 (mean +/- SEM) for the AA and AAA groups, respectively. The average Ethetatheta,max at 200 N/m equibiaxial tension was found to be significantly smaller for AAAs as compared to AAs (0.07 +/- 0.01 versus 0.13 +/- 0.03, respectively; p < 0.01). There was also a pronounced increase in the circumferential stiffness for AAA tissue as compared to AA tissue, indicating a larger degree of anisotropy for this tissue as compared to age-matched AA tissue. We also observed that the four-parameter Fung-elastic model was not able to fit the AAA tissue mechanical response using physically realistic material parameter values. It was concluded that aneurysmal degeneration of the abdominal aorta is associated with an increase in mechanical anisotropy, with preferential stiffening in the circumferential direction.     

Distribution of stress and strain along the porcine aorta and coronary arterial tree

The existence of a homeostatic state of stresses and strains has been axiomatic in the cardiovascular system. The objective of this study was to determine the distribution of circumferential stress and strain along the aorta and throughout the coronary arterial tree to test this hypothesis. Silicone elastomer was perfused through the porcine aorta and coronary arterial tree to cast the arteries at physiological pressure. The loaded and zero-stress dimensions of the vessels were measured. The aorta (1.8 cm) and its secondary branches were considered down to 1.5 mm diameter. The left anterior descending artery (4.5 mm) and its branches down to 10 microm were also measured. The Cauchy mean circumferential stress and midwall stretch ratio were calculated. Our results show that the stretch ratio and Cauchy stress were lower in the thoracic than in the abdominal aorta and its secondary branches. The opening angle (theta) and midwall stretch ratio (lambda) showed a linear variation with order number (n) as follows: theta = 10.2n + 63.4 (R(2) = 0.989) and lambda = 4.47 x 10(-2)n + 1.1 (R(2) = 0.995). Finally, the stretch ratio and stress varied between 1.2 and 1.6 and between 10 and 150 kPa, respectively, along the aorta and left anterior descending arterial tree. The relative uniformity of strain (50% variation) from the proximal aorta to a 10-microm arteriole implies that the vascular system closely regulates the degree of deformation. This suggests a homeostasis of strain in the cardiovascular system, which has important implications for mechanotransduction and for vascular growth and remodeling.     

A planar biaxial constitutive relation for the luminal layer of intra-luminal thrombus in abdominal aortic aneurysms

The rupture risk of abdominal aortic aneurysms (AAAs) is thought to be associated with increased levels of wall stress. Finite element analysis (FEA) allows the prediction of wall stresses in a patient-specific, non-invasive manner. We have recently shown that it is important to include the intra-luminal thrombus (ILT), present in approximately 70% of AAA, into FEA simulations of AAA. All FEA simulations to date assume an isotropic, homogeneous material behavior for this material. The purpose of this work was to investigate the multi-axial biomechanical behavior of ILT and to derive an appropriate constitutive relation. We performed planar biaxial testing on the luminal layer of nine ILT specimens obtained fresh in the operating room (9 patients, mean age 71+/-4.5 years, mean diameter 5.9+/-0.4 cm), and a constitutive relation was derived from this data. Peak stretch and maximum tangential modulus (MTM) values were recorded for the equibiaxial protocol in both the circumferential (theta) and longitudinal (L) directions. Stress contour plots were used to investigate the presence of mechanical anisotropy, after which an appropriate strain energy function was fit to each of the specimen datasets. The peak stretch values for the luminal layer of the ILT were (mean+/-SEM) 1.18+/-0.02 and 1.13+/-0.02 in the theta and L directions, respectively (p=0.14). The MTM values were 20+/-2 and 23+/-3N/cm(2) in the theta and L directions, respectively (p=0.37). From these results and our observation of the symmetry of the stress contour plots for each specimen, we concluded that the use of an isotropic strain energy function for ILT is appropriate. Each specimen data set was then fit to a second-order polynomial strain energy function of the first invariant of the left Cauchy-Green strain tensor, resulting in an accurate fit (average R(2)=0.92+/-0.02; range 0.80-0.99). Comparison of our previously reported, uniaxially derived constitutive relation with the biaxially derived relation derived here shows large differences in the predicted mechanical response, underscoring the importance of the appropriate experimental methods used to derive constitutive relations. Further work is merited in an effort to produce more accurate predictions of wall stresses in patient-specific AAA, and viscoelastic behaviors of the ILT.     

Mechanical properties of spinal nerve roots subjected to tension at different strain rates

An understanding of the biomechanical and physiological properties of spinal nerve roots, particularly in response to tension, is critical in understanding the pathomechanisms of pain and nerve root injury and subsequent management of related injuries. Biomechanical properties of dorsal nerve roots at the lumbar and sacral levels were evaluated at various strain rates. Nerve roots were stretched at two different rates, 0.01 mm/s (Group A, quasistatic) and 15 mm/s (Group B, dynamic). Load, displacement and digital video data were obtained as the nerve roots were stretched until failure. Maximum stress, strain at maximum stress and modulus of elasticity (E) were calculated from the load-displacement measurements. Comparison of mechanical properties and failure patterns of nerve roots at two different rates revealed significant differences. Maximum load, maximum stress and E values of 5.7+/-2.7 gm, 257.9+/-111.3 kPa and 1.3+/-0.8 MPa were observed for Group A and 13.9+/-7.5 gm, 624.9+/-306.8 kPa and 2.9+/-1.5 MPa were observed for Group B, respectively. Higher maximum load, maximum stress and E values occurred at the dynamic stretch rate as compared to the quasistatic stretch rate, illustrating the strain-rate dependency of spinal nerve roots. No differences were observed in the strain values. Differences in mechanical behavior of nerve roots were also observed among the four root levels (L4-S1). A significant interaction effect was observed between nerve root diameter and stretch rates. Overall, results from the present study demonstrate viscoelastic material properties of spinal nerve roots and provide better insight on the tensile properties of nerve roots at different strain rates.     

Influence of tensile strain on smooth muscle cell orientation in rat blood vessels.

Blood vessels are subject to tensile stress and associated strain which may influence the structure and organization of smooth muscle cells (SMCs) during physiological development and pathological remodeling. This study focused on the influence of the major tensile strain on the SMC orientation in the blood vessel wall. Several blood vessels, including the aorta, the mesenteric artery and vein, and the jugular vein of the rat were used to observe the normal distribution of tensile strains and SMC orientation; and a vein graft model was used to observe the influence of altered strain direction on the SMC orientation. The circumferential and longitudinal strains in these blood vessels were measured by using a biomechanical technique, and the SMC orientation was examined by fluorescent microscopy at times of 10, 20, and 30 days. Results showed that the SMCs were mainly oriented in the circumferential direction of straight blood vessels with an average angle of approximately 85 deg between the SMC axis and the vessel axis in all observed cases. The SMC orientation coincided with the principal direction of the circumferential strain, a major tensile strain, in the blood vessel wall. In vein grafts, the major tensile strain direction changed from the circumferential to the longitudinal direction at observation times of 10, 20, and 30 days after graft surgery. This change was associated with a decrease in the angle between the axis of newly proliferated SMCs and that of the vessel at all observation times (43 +/- 11 deg, 42 +/- 10 deg, and 41 +/- 10 deg for days 10, 20, and 30, respectively), indicating a shift of the SMC orientation from the circumferential toward the longitudinal direction. These results suggested that the major tensile strain might play a role in the regulation of SMC orientation during the development of normal blood vessels as well as during remodeling of vein grafts.     

Pipette aspiration technique for the measurement of nonlinear and anisotropic mechanical properties of blood vessel walls under biaxial stretch

A pipette aspiration technique was proposed for the measurement of nonlinear mechanical properties of arteries under biaxial stretching. A cross-shaped specimen of porcine thoracic aorta whose principal axes corresponded with the axial and circumferential directions of the aortic walls was excised. The intraluminal surface of the specimen was aspirated with a circular cross-sectioned glass pipette while the specimen was stretching in the axial and circumferential directions in 10% increments. The elastic modulus agreed with the incremental elastic modulus obtained through a conventional pressure-diameter test of the same specimen to within an error of 30% at a circumferential stretch ratio below 1.3 and an axial stretch ratio of 1.0, 1.1 or 1.2, which represent lower range of physiological stretch ratios for the porcine aorta. A rectangular cross-sectioned pipette was utilized to measure anisotropic properties of the specimen under biaxial stretching. When aspirated with such a pipette, the specimens' elastic properties along the length of the rectangular pipette cross section can be neglected. The elastic modulus was found to increase rapidly when the specimen was stretched in the direction of the pipette's width. Thus, pipette aspiration should have many advantages such as well measurement of the local nonlinear and anisotropic mechanical properties of blood vessel walls.     

The effect of progestin and GnRH treatments on ovarian function and reproductive hormone secretions of anestrous postpartum suckled beef cows

Eighteen anestrous crossbred suckled beef cows were assigned to one of three treatment groups. Treatments were as follows: Group 1 cows (n = 3) were untreated and served as controls, Groups 2 cows (n = 6) were intramuscularly administered 250 mug GnRH, and Group 3 cows (n = 9) were subcutaneously administered a progestin ear implant for eight days prior to the administration of 250 mug GnRH. The GnRH was given to cows in Group 3 24 h after the time of progestin implant removal. Cows were 21 to 31 days postpartum at the time of GnRH treatment. The percent of cows that ovulated after the time of GnRH treatment was 0%, 83% and 100% for Groups 1, 2 and 3, respectively. For the cows that ovulated, more (P < 0.05) cows in Group 2 (80%) had abnormal luteal phases than in Group 3 (33%). The GnRH-induced LH release and peak LH concentrations were greater (P < 0.01) in the cows in Group 3 (214.3 +/- 37.1 ng/ml) than in the cows in Group 2 (142.7 +/- 19.0 ng/ml). The LH concentrations of the control cows remained very low throughout the sampling period. Although prostaglandin metabolite (PGFM) concentrations were not significantly (P > 0.10) different among groups, mean concentrations were higher and more variable for cows in Groups 1 (39.2 +/- 5.2 pg/ml) and 2 (39.4 + 6.1 pg/ml) than for cows in Group 3 (25.1 + 1.4 pg/ml).     

Linked mechanical and biological aspects of remodeling in mouse pulmonary arteries with hypoxia-induced hypertension

Supravalvular aortic stenosis (SVAS) is associated with decreased elastin and altered arterial mechanics. Mice with a single deletion in the elastin gene (ELN(+/-)) are models for SVAS. Previous studies have shown that elastin haploinsufficiency in these mice causes hypertension, decreased arterial compliance, and changes in arterial wall structure. Despite these differences, ELN(+/-) mice have a normal life span, suggesting that the arteries remodel and adapt to the decreased amount of elastin. To test this hypothesis, we performed in vitro mechanical tests on abdominal aorta, ascending aorta, and left common carotid artery from ELN(+/-) and wild-type (C57BL/6J) mice. We compared the circumferential and longitudinal stress-stretch relationships and residual strains. The circumferential stress-stretch relationship is similar between genotypes and changes <3% with longitudinal stretch at lengths within 10% of the in vivo value. At mean arterial pressure, the circumferential stress in the ascending aorta is higher in ELN(+/-) than in wild type. Although arterial pressures are higher, the increased number of elastic lamellae in ELN(+/-) arteries results in similar tension/lamellae compared with wild type. The longitudinal stress-stretch relationship is similar between genotypes for most arteries. Compared with wild type, the in vivo longitudinal stretch is lower in ELN(+/-) abdominal and carotid arteries and the circumferential residual strain is higher in ELN(+/-) ascending aorta. The increased circumferential residual strain brings the transmural strain distribution in ELN(+/-) ascending aorta close to wild-type values. The mechanical behavior of ELN(+/-) arteries is likely due to the reduced elastin content combined with adaptive remodeling during vascular development.     

Gonadotrophin secretion and ovarian responses in prepubertal heifers actively immunized against androstenedione and oestradiol-17 beta

Groups of heifer calves received a primary immunization against androstenedione (Group A; N = 11) or oestradiol-17 beta (Group E; N = 10) at 3 months of age and booster injections on 5 occasions at 2- to 3-month intervals. Controls (Group C, N = 11) were immunized against human serum albumin alone using the same protocol. Immunity was achieved against both steroids as judged by the secondary antisteroid antibody titres in Group A (1126 +/- 261; reciprocal of titre) and Group E (10,357 +/- 4067) heifers. In Groups A and E there was a general decline in the respective peak antibody titres after successive booster injections. From 3 to 9 months of age mean plasma concentrations of LH were higher (P less than 0.05) in Group E heifers (0.89 +/- 0.08 ng/ml) than in Group C (0.46 +/- 0.03 ng/ml) and Group A (0.59 +/- 0.05 ng/ml) heifers which did not differ from one another. There were no differences between groups in plasma FSH concentrations. At 10 months of age the LH response to exogenous LHRH was of higher (P less than 0.05) amplitude for heifers in Group E (2.59 +/- 0.56 ng/ml) than for those in Groups C (0.61 +/- 0.07 ng/ml) and A (1.04 +/- 0.22 ng/ml). Elevated plasma progesterone concentrations at 5 months of age were shown by 2 heifers in Group C, 10 in Group A, and 6 in Group E. From 8 to 14 months of age a consistently higher proportion of Group A heifers exhibited elevated progesterone compared with Group C and Group E heifers. After ovarian synchronization and booster injection at 15 months of age a corpus luteum was present in 2 heifers in Group C, 7 in Group A and none in Group E. The ovaries of Group A heifers were different from those of Groups C and E and were characterized by greater numbers of 2-4 mm follicles. It is concluded that active immunization against gonadal steroids influences both LH secretion and ovarian function in prepubertal heifers. Early increases in ovarian activity in androstenedione-immunized heifers are maintained after puberty and may therefore confer some lifetime reproductive advantages.     

The effects of angiotensin II on the coupled microstructural and biomechanical response of C57BL/6 mouse aorta

RationaleAbdominal aortic aneurysm (AAA) is a complex disease that leads to a localized dilation of the infrarenal aorta, the rupture of which is associated with significant morbidity and mortality. Animal models of AAA can be used to study how changes in the microstructural and biomechanical behavior of aortic tissues develop as disease progresses in these animals. We chose here to investigate the effect of angiotensin II (AngII) in C57BL/6 mice as a first step towards understanding how such changes occur in the established ApoE^?/? AngII infused mouse model of AAA.ObjectiveThe objective of this study was to utilize a recently developed device in our laboratory to determine how the microstructural and biomechanical properties of AngII-infused C57BL/6 wildtype mouse aorta change following 14 days of AngII infusion.MethodsC57BL/6 wildtype mice were infused with either saline or AngII for 14 day. Aortas were excised and tested using a device capable of simultaneously characterizing the biaxial mechanical response and load-dependent (unfixed, unfrozen) extracellular matrix organization of mouse aorta (using multiphoton microscopy). Peak strains and stiffness values were compared across experimental groups, and both datasets were fit to a Fung-type constitutive model. The mean mode and full width at half maximum (FWHM) of fiber histograms from two photon microscopy were quantified in order to assess the preferred fiber distribution and degree of fiber splay, respectively.ResultsThe axial stiffness of all mouse aorta was found to be an order of magnitude larger than the circumferential stiffness. The aortic diameter was found to be significantly increased for the AngII infused mice as compared to saline infused control (p=0.026). Aneurysm, defined as a percent increase in maximum diameter of 30% (defined with respect to saline control), was found in 3 of the 6 AngII infused mice. These three mice displayed adventitial collagen that lacked characteristic fiber crimp. The biomechanical response in the AngII infused mice showed significantly reduced circumferential compliance. We also noticed that the ability of the adventitial collagen fibers in AngII infused mice to disperse in reaction to circumferential loading was suppressed.ConclusionsCollagen remodeling is present following 14 days of AngII infusion in C57BL/6 mice. Aneurysmal development occurred in 50% of our AngII infused mice, and these dilatations were accompanied with adventitial collagen remodeling and decreased circumferential compliance.     

A comparison of uniaxial and biaxial mechanical properties of the annulus fibrosus: a porcine model

The annulus fibrosus of the intervertebral disk experiences multidirectional tension in vivo, yet the majority of mechanical property testing has been uniaxial. Therefore, our understanding of how this complex multilayered tissue responds to loading may be deficient. This study aimed to determine the mechanical properties of porcine annular samples under uniaxial and biaxial tensile loading. Two-layer annulus samples were isolated from porcine disks from four locations: anterior superficial, anterior deep, posterior superficial, and posterior deep. These tissues were then subjected to three deformation conditions each to a maximal stretch ratio of 1.23: uniaxial, constrained uniaxial, and biaxial. Uniaxial deformation was applied in the circumferential direction, while biaxial deformation was applied simultaneously in the circumferential and compressive directions. Constrained uniaxial consisted of a stretch ratio of 1.23 in the circumferential direction while holding the tissue stationary in the axial direction. The maximal stress and stress-stretch ratio (S-S) moduli determined from the biaxial tests were significantly higher than those observed during both the uniaxial tests (maximal stress, 97.1% higher during biaxial; p=0.002; S-S moduli, 117.9% higher during biaxial; p=0.0004) and the constrained uniaxial tests (maximal stress, 46.8% higher during biaxial; S-S moduli, 82.9% higher during biaxial). These findings suggest that the annulus is subjected to higher stresses in vivo when under multidirectional tension.     

Mechanical anisotropy of inflated elastic tissue from the pig aorta

Uniaxial and biaxial mechanical properties of purified elastic tissue from the proximal thoracic aorta were studied to understand physiological load distributions within the arterial wall. Stress–strain behaviour was non-linear in uniaxial and inflation tests. Elastic tissue was 40% stiffer in the circumferential direction compared to axial in uniaxial tests and～100% stiffer in vessels at an axial stretch ratio of 1.2 or 1.3 and inflated to physiological pressure. Poisson’s ratio v_θz averaged 0.2 and v_zθ increased with circumferential stretch from ～0.2 to ～0.4. Axial stretch had little impact on circumferential behaviour. In intact (unpurified) vessels at constant length, axial forces decreased with pressure at low axial stretches but remained constant at higher stretches. Such a constant axial force is characteristic of incrementally isotropic arteries at their in vivo dimensions. In purified elastic tissue, force decreased with pressure at all axial strains, showing no trend towards isotropy. Analysis of the force–length–pressure data indicated a vessel with v_θz≈0.2 would stretch axially 2–4% with the cardiac pulse yet maintain constant axial force. We compared the ability of 4 mathematical models to predict the pressure-circumferential stretch behaviour of tethered, purified elastic tissue. Models that assumed isotropy could not predict the stretch at zero pressure. The neo-Hookean model overestimated the non-linearity of the response and two non-linear models underestimated it. A model incorporating contributions from orthogonal fibres captured the non-linearity but not the zero-pressure response. Models incorporating anisotropy and non-linearity should better predict the mechanical behaviour of elastic tissue of the proximal thoracic aorta.     

Effect of expectorants on relaxation behavior of sputum viscoelasticity in vivo

We studied the effects of expectorants (mucolytic agents) in vivo on the relaxation behavior of sputum viscoelasticity. Seven female and thirty-three male patients (56.8 +/- 19.3 yrs, range: 21 to 82 years old) with a chronic pulmonary disease except bronchial asthma were studied. They were randomly put into the control group or a group which would be given oral treatments with an expectorant for a week after a one week washout period. The groups were as follows: Group I (n = 8), control; Group II (n = 7), Bromhexine hydrochloride 24 mg per day; Group III (n = 10), Ambroxol 90 mg per day; Group IV (n = 9) alpha - Chymotrypsin buccle 100 ch.u. per day; Group V (n = 6), Serratiopeptidase 30 mg per day. In Groups IV & V, frequency dependence of sputum viscoelasticity at the range of omega = 10(-3) to 10(0) rad.sec-1 were clearly changed after the treatments, and the magnitude of the relaxation and its main relaxation time were significantly increased. On the other hand, in Groups I, II & III, no significant changes of the frequency dependences were observed. These findings suggest that proteolytic enzymes administered orally work on the molecular structure of sputum, and break down their linkages between subunits of the structure.     

Direct biomechanical induction of endogenous calcineurin inhibitor Down Syndrome Critical Region-1 in cardiac myocytes

Signaling through the protein phosphatase calcineurin may play a critical role in cardiac hypertrophy. The gene for Down Syndrome Critical Region-1 (DSCR1) encodes a protein that is an endogenous calcineurin inhibitor. This study was designed to test the hypothesis that DSCR1 is directly induced by biomechanical stimuli. Neonatal rat cardiac myocytes were exposed to biaxial cyclic mechanical strain; mechanical strain upregulated DSCR1 mRNA expression in a time- and amplitude-dependent manner (3.4 +/- 0.2-fold at 8% strain for 6 h, n = 11, P < 0.01), and this induction was angiotensin II and endothelin I independent. Biomechanical induction of DSCR1 mRNA was partially blocked by calcineurin inhibition with cyclosporine A (30 +/- 5%, n = 3, P < 0.01). DSCR1 promoter-reporter experiments showed that mechanical strain induced DSCR1 promoter activity by 2.3-fold and that this induction was completely inhibited by cyclosporin A. Furthermore, DSCR1 gene expression was increased in the left ventricles of mice with pressure-overload hypertrophy induced by transverse aortic banding. These data demonstrate that biomechanical strain directly induces gene expression for the calcineurin inhibitor DSCR1 in cardiac myocytes, indicating that mechanically induced DSCR1 may regulate the hypertrophic response to mechanical overload.     

Comparison of weighted jump squat training with and without eccentric braking

The purpose of this study was to investigate the effect of weighted jump squat training with and without eccentric braking. Twenty male subjects were divided into two groups (n = 10 per group), Non-Braking Group and Braking Group. The subjects were physically active, but not highly trained. The program for Non-Braking Group consisted of 6 sets of 6 repetitions of weighted jump squats without reduction of eccentric load for 8 weeks. The training program for the Braking Group consisted of the same sets and repetitions, but eccentric load was reduced by using an electromagnetic braking mechanism. Jump and reach, countermovement jump, static jump, drop jump, one repetition maximum half squat, weighted jump squat, and isometric/isokinetic knee extension/flexion at several different positions/angular velocities were tested pre- and posttraining intervention. The Non-Braking Group exhibited greater improvement in peak torque during isokinetic concentric knee flexion at 300 degrees/s [Non-Braking Group: (mean +/- SD) 124.0 +/- 22.6 Nm at pre- and 134.1 +/- 18.4 Nm at posttraining, and Braking Group: 118.5 +/- 32.7 Nm at pre- and 113.2 +/- 26.7 Nm at posttraining]. Braking Group exhibited superior adaptations in peak power relative to body mass during weighted jump squat [Non-Braking Group: (mean +/- SD) 49.1 +/- 8.6 W/kg at pre- and 50.9 +/- 6.2 W/kg at posttraining, and Braking Group: 47.9 +/- 6.9 W/kg at pre- and 53.7 +/- 7.3 W/kg at posttraining]. It appears that power output in relatively slow movement (weighted jump squat) was improved more in the Braking Group, however strength in high velocity movements (isokinetic knee flexion at 300 degrees/s) was improved more in Non-Braking Group. This study supports load and velocity specific effects of weighted jump squat training.     

Measurements of mouse pulmonary artery biomechanics

BACKGROUND: Robust techniques for characterizing the biomechanical properties of mouse pulmonary arteries will permit exciting gene-level hypotheses regarding pulmonary vascular disease to be tested in genetically engineered animals. In this paper, we present the first measurements of the biomechanical properties of mouse pulmonary arteries. METHOD OF APPROACH: In an isolated vessel perfusion system, transmural pressure, internal diameter and wall thickness were measured during inflation and deflation of mouse pulmonary arteries over low (5-40 mmHg) and high (10-120 mmHg) pressure ranges representing physiological pressures in the pulmonary and systemic circulations, respectively. RESULTS: During inflation, circumferential stress versus strain showed the nonlinear "J"-shape typical of arteries. Hudetz's incremental elastic modulus ranged from 27 +/- 13 kPa (n = 7) during low-pressure inflation to 2,700 +/- 1,700 kPa (n = 9) during high-pressure inflation. The low and high-pressure testing protocols yielded quantitatively indistinguishable stress-strain and modulus-strain results. Histology performed to assess the state of the tissue after mechanical testing showed intact medial and adventitial architecture with some loss of endothelium, suggesting that smooth muscle cell contractile strength could also be measured with these techniques. CONCLUSIONS: The measurement techniques described demonstrate the feasibility of quantifying mouse pulmonary artery biomechanical properties. Stress-strain behavior and incremental modulus values are presented for normal, healthy arteries over a wide pressure range. These techniques will be useful for investigations into biomechanical abnormalities in pulmonary vascular disease.     

Evolving biaxial mechanical properties of mouse carotid arteries in hypertension

Quantifying the time course of load-induced changes in arterial wall geometry, microstructure, and properties is fundamental to developing mathematical models of growth and remodeling. Arteries adapt to altered pressure and flow by modifying wall thickness, inner diameter, and axial length via marked cell and matrix turnover. To estimate particular biomaterial implications of such adaptations, we used a 4-fiber family constitutive relation to quantify passive biaxial mechanical behaviors of mouse carotid arteries 0 (control), 7-10, 10-14, or 35-56 days after an aortic arch banding surgery that increased pulse pressure and pulsatile flow in the right carotid artery. In vivo circumferential and axial stretches at mean arterial pressure were, for example, 11% and 26% lower, respectively, in hypertensive carotids 35-56 days after banding than in normotensive controls; this finding is consistent with observations that hypertension decreases distensibility. Interestingly, the strain energy W stored in the carotids at individual in vivo conditions was also less in hypertensive compared with normotensive carotids. For example, at 35-56 days after banding, W was 24%, 39%, and 47% of normal values at diastolic, mean, and systolic pressures, respectively. The energy stored during the cardiac cycle, W(sys)-W(dias), also tended to be less, but this reduction did not reach significance. When computed at normal in vivo values of biaxial stretch, however, W was well above normal for the hypertensive carotids. This net increase resulted from an overall increase in the collagen-related anisotropic contribution to W despite a decrease in the elastin-related isotropic contribution. The latter was consistent with observed decreases in the mass fraction of elastin.     

Use of a GnRH agonist to prevent the endogenous LH surge and injection of exogenous LH to induce ovulation in heifers superstimulated with FSH: a new model for superovulation

A new protocol for superovulating cattle which allows for control of the timing of ovulation after superstimulation with FSH was developed. The preovulatory LH surge was blocked with the GnRH agonist deslorelin, and ovulation was induced by injection of LH. In Experiment 1, heifers (3-yr-old) were assigned to a control group (Group 1A, n = 4) or a group with deslorelin implants (Group 1B, n = 5). On Day -7, heifers in Group 1A received a progestagen CIDR-B((R))device, while heifers in Group 1B received a CIDR-B((R))device + deslorelin implants. Both groups were superstimulated with twice daily injections of FSH (Folltropin((R))-V): Day 0, 40 mg (80 mg total dose on Day 0); Day 1, 30 mg; Day 2, 20 mg; Day 3, 10 mg. On Day 2, heifers were given PGF (a.m.) and CIDR-B((R)) devices were removed (p.m.). Three heifers in Group 1A had a LH surge and ovulated, whereas neither of these events occurred in Group 1B (with deslorelin implants) heifers. In Experiment 2, heifers (3-yr-old) were assigned to 1 of 4 equal groups (n = 6). On Day -7, heifers in Group 2A received a norgestomet implant, while heifers in Groups 2B, 2C and 2D received norgestomet + deslorelin implants. Heifers were superstimulated with FSH starting on Day 0 as in Experiment 1. On Day 2, heifers were given PGF (a.m.) and norgestomet implants were removed (p.m.). Heifers in Groups 2B to 2D were given 25 mg LH (Lutropin((R))): Group 2B, Day 4 (a.m.); Group 2C, Day 4 (p.m.); Group 2D, Day 5 (a.m.). Heifers in Group 2A were inseminated at estrus and 12 and 24 h later, while heifers in Groups 2B to 2D were inseminated at the time of respective LH injection and 12 and 24 h later. Injection of LH induced ovulation in heifers in Groups 2B to 2D. Heifers in Group 2C had similar total ova and embryos (15.2 +/- 1.4) as heifers in Group 2A (11.0 +/- 2.8) but greater (P < 0.05) numbers than heifers in Group 2B (7.0 +/- 2.3) and Group 2D (6.3 +/- 2.0). The number of transferable embryos was similar for heifers in Group 2A (5.8 +/- 1.8) and Group 2C (7.3 +/- 2.1) but lower (P < 0.05) for heifers in Group 2B (1.2 +/- 0.8) and Group 2D (1.3 +/- 1.0). The new GnRH agonist-LH protocol does not require observation of estrus, and induces ovulation in superstimulated heifers that would not have an endogenous LH surge.     

Inferior vena caval hemodynamics quantified in vivo at rest and during cycling exercise using magnetic resonance imaging

Compared with the abdominal aorta, the hemodynamic environment in the inferior vena cava (IVC) is not well described. With the use of cine phase-contrast magnetic resonance imaging (MRI) and a custom MRI-compatible cycle in an open magnet, we quantified mean blood flow rate, wall shear stress, and cross-sectional lumen area in 11 young normal subjects at the supraceliac and infrarenal levels of the aorta and IVC at rest and during dynamic cycling exercise. Similar to the aorta, the IVC experienced significant increases in blood flow and wall shear stress as a result of exercise, with greater increases in the infrarenal level compared with the supraceliac level. At the infrarenal level during resting conditions, the IVC experienced higher mean flow rate than the aorta (1.2 +/- 0.5 vs. 0.9 +/- 0.4 l/min, P < 0.01) and higher mean wall shear stress than the aorta (2.0 +/- 0.6 vs. 1.3 +/- 0.6 dyn/cm(2), P < 0.005). During exercise, wall shear stress remained higher in the IVC compared with the aorta, although not significantly. It was also observed that, whereas the aorta tapers inferiorly, the IVC tapers superiorly from the infrarenal to the supraceliac location. The hemodynamic and anatomic data of the IVC acquired in this study add to our understanding of the venous circulation and may be useful in a clinical setting.     

Mechanical discoordination rather than dyssynchrony predicts reverse remodeling upon cardiac resynchronization

By current guidelines a considerable part of the patients selected for cardiac resynchronization therapy (CRT) do not respond to the therapy. We hypothesized that mechanical discoordination [opposite strain within the left ventricular (LV) wall] predicts reversal of LV remodeling upon CRT better than mechanical dyssynchrony. MRI tagging images were acquired in CRT candidates (n = 19) and in healthy control subjects (n = 9). Circumferential strain (epsilon(cc)) was determined in 160 regions. From epsilon(cc) signals we derived 1) an index of mechanical discoordination [internal stretch fraction (ISF), defined as the ratio of stretch to shortening during ejection] and 2) indexes of mechanical dyssynchrony: the 10-90% width of time to onset of shortening, time to peak shortening, and end-systolic strain. LV end-diastolic volume (LVEDV), end-systolic volume (LVESV), and ejection fraction (LVEF) were determined before and after 3 mo of CRT. Responders were defined as those patients in whom LVESV decreased by >15%. In responders (n = 10), CRT increased LVEF and decreased LVEDV and LVESV (11 +/- 6%, 21 +/- 16%, and 30 +/- 16%, respectively) significantly more (P < 0.05) than in nonresponders (1 +/- 6%, 3 +/- 4%, and 5 +/- 10%, respectively). Among mechanical indexes, only ISF was different between responders and nonresponders (0.53 +/- 0.25 vs. 0.31 +/- 0.16; P < 0.05). In patients with ISF >0.4 (n = 10), LVESV decreased by 31 +/- 18% vs. 5 +/- 11% in patients with ISF <0.4 (P < 0.05). We conclude that mechanical discoordination, as estimated from ISF, is a better predictor of reverse remodeling after CRT than differences in time to onset and time to peak shortening. Therefore, discoordination rather than dyssynchrony appears to reflect the reserve contractile capacity that can be recruited by CRT.