Biomechanical properties of decellularized porcine common carotid arteries

To analyze the effects of decellularization on the biomechanical properties of porcine common carotid arteries, decellularization was performed by a detergent-enzymatic procedure that preserves extracellular matrix scaffold. Internal diameter, external diameter, and wall thickness were measured by optical microscopy on neighboring histological sections before and after decellularization. Rupture tests were conducted. Inner diameter and wall thickness were measured by echo tracking during pressure inflation from 10 to 145 mmHg. Distensibility and incremental elastic modulus were computed. At 10 mmHg, mean diameter of decellularized arteries was 5.38 mm, substantially higher than controls (4.1 mm), whereas decellularized and control arteries reached the same internal diameter (6.7 mm) at 145 mmHg. Wall thickness decreased 16% for decellularized and 32% for normal arteries after pressure was increased from 10 to 145 mmHg. Decellularized arteries withstood pressure >2,200 mmHg before rupture. At 145 mmHg, decellularization reduced compliance by 66% and increased incremental elastic modulus by 54%. Removal of cellular elements from media led to changes in arterial dimensions. Collagen fibers engaged more rapidly during inflation, yielding a stiffer vessel. Distensibility was therefore significantly lower (by a factor of 3) in decellularized than in normal vessels: reduced in the physiological range of pressures. In conclusion, decellularization yields vessels that can withstand high inflation pressures with, however, markedly different geometrical and biomechanical properties. This may mean that the potential use of a decellularized artery as a scaffold for the creation of xenografts may be compromised because of geometrical and compliance mismatch.     

Active and passive properties of carotid arteries]

A mathematical model of carotid arteries is constructed from the known experimental data. Passive properties of the vascular wall are characterized by an alternating module of elasticity, the active ones by the specific power of muscle contraction. Its maximum value (0,023 n/m-3) is shown to be reached with intravascular pressure 190 mm Hg. The dependence of inner radius on the power of muscle contraction is studied at different values of intravascular pressure. It is shown that theactive properties of carotid arteries are essentially determined by their passive properties and depend on the stretching of the vessel wall.     

Age and sex dependence of hemodynamic parameters of human internal carotid arteries

The study of the ultrasound diameter, linear velocity, and resistance of the internal carotid arteries in 647 subjects of both sexes aged from 1 to 74 years has been performed. Additionally, shear stress and the Reynolds number have been calculated. During the period from early childhood to adolescence and from the first mature to younger elderly ages, there is an increase in the diameter of the internal carotid arteries. Phases of an increase in the vascular resistance by the first period of childhood, adolescence, and younger elderly age are observed. The space flow velocity has relatively stable parameters till youth, and then it declines by younger elderly age. The average linear velocity, shear stress, and the Reynolds number progressively diminish twice by younger elderly age. Laminar blood flow with local twists in the early stages of postnatal ontogenesis is characteristic of the internal carotid arteries. The diameter of the internal carotid arteries, vascular resistance index, and blood flow velocity are higher in men than in women during most age periods. Shear stress in both internal carotid arteries during all the age periods studied is symmetrical and has no sex differences.     

Condition of the internal arterial and microcirculatory bed of the neck muscles of the dog after simultaneous ligation of the common carotid and vertebral arteries

In 21 mongrel dogs changes in the intraorganic arterial and microcirculatory bed of the cervical muscles have been studied after a simultaneous ligation of the common carotid and vertebral arteries. The most pronounced changes of rearrangement are observed during early periods after the operation (up to two months). The form, size of the arterial loops and direction of the blood stream change in them. On the base of the arterio-arterial anastomoses collateralies are formed, their degree of development is progressing with the increase of the postoperative time. The arteriolo-arteriolar anastomoses in small loops convert into microvascular collateralies that are of importance only during early postoperative stages. The new conditions of hemodynamics at the arteriolar level result in a dependent rearrangement in other links of the microcirculatory bed, where a number of compensatory-adaptive mechanisms are revealed. After the magistral by-pass ways are completely formed, the changes observed disappear and the microcirculatory network acquires the features specific for intact animals.     

Methodology to study intimal failure mechanics in human internal carotid arteries

While the incidence of blunt carotid artery injuries is low, the mortality rate is extremely high (40%). Clinical evidence indicates that the intimal region of the artery often sustains failure, while maintaining the integrity of the outer layers. This condition may lead to delayed ischemic symptoms, commonly reported in clinical literature. To date, the mechanical properties of the intima relative to the outer vessel layers have not been quantified in the human carotid artery. The purpose of the present study was to develop a methodology to determine the longitudinal mechanical properties of the human internal carotid artery in tension, with an emphasis on intimal failure. This was accomplished by opening the vessel at the mid-diameter level, creating an ‘I’-shaped testing specimen, subjecting the specimen to failure loading, documenting the stretch characteristics of the intimal and adventitial sides in the temporal domain, and correlating the synchronized videography with mechanical loading. Intimal failure data were quantified using stress and strain parameters in conjunction with digital videography of the intimal and adventitial sides. The present methodology can be used to determine the mechanical properties of the intima relative to ultimate carotid artery failure. These data will assist in the understanding of blunt carotid artery injuries, its diagnosis and treatment.     

Pharmacological characterization of the mechanisms involved in the vasorelaxation induced by progesterone and 17β-estradiol on isolated canine basilar and internal carotid arteries

Progesterone and 17β-estradiol induce vasorelaxation through non-genomic mechanisms in several isolated blood vessels; however, no study has systematically evaluated the mechanisms involved in the relaxation induced by 17β-estradiol and progesterone in the canine basilar and internal carotid arteries that play a key role in cerebral circulation. Thus, relaxant effects of progesterone and 17β-estradiol on KCl- and/or PGF_2α-pre-contracted arterial rings were investigated in absence or presence of several antagonists/inhibitors/blockers; the effect on the contractile responses to CaCl₂ was also determined. In both arteries progesterone (5.6–180 μM) and 17β-estradiol (1.8–180 μM): (1) produced concentration-dependent relaxations of KCl- or PGF_2α-pre-contracted arterial rings; (2) the relaxations were unaffected by actinomycin D (10 μM), cycloheximide (10 μM), SQ 22,536 (100 μM) or ODQ (30 μM), potassium channel blockers and ICI 182,780 (only for 17β-estradiol). In the basilar artery the vasorelaxation induced by 17β-estradiol was slightly blocked by tetraethylammonium (10 mM) and glibenclamide (K_ATP; 10 μM). In both arteries, progesterone (10–100 μM), 17β-estradiol (3.1–31 μM) and nifedipine (0.01–1 μM) produced a concentration-dependent blockade of the contraction to CaCl₂ (10 μM–10 mM). These results suggest that progesterone and 17β-estradiol produced relaxation in the basilar and internal carotid arteries by blockade of L-type voltage dependent Ca²⁺ channel but not by genomic mechanisms or production of cAMP/cGMP. Potassium channels did not play a role in the relaxation to progesterone in both arteries or in the effect of 17β-estradiol in the internal carotid artery; meanwhile K_ATP channels play a minor role on the effect of 17β-estradiol in the basilar artery.     

Experimental determination of wall shear rate in canine carotid arteries perfused in vitro

The mathematical model of Hung (Tsai and Hung, 1984) is employed to determine the wall shear rate acting on canine carotid arteries perfused in vitro. Model equations for pulsatile flow in a deformable vessel are coupled with experimental data of dynamic pressure drop, flow rate, vessel radius and radial wall motion. Derived quantities, e.g. velocity profiles and wall shear, are obtained for vessels exposed to 'normotensive' hemodynamics, 'hypertension' simulations and perfusions in which the compliance of the vessel wall is deliberately altered. Our results indicate that wall shear varies markedly as a function of the hemodynamic environment. The effects of vessel radius vs flow rate on the development of wall shear are also demonstrated. It is found that convective processes correlate with the magnitude of wall shear in the 'hypertension' simulations. The present findings and complementary published data may explain, at least in part, the variations in vessel wall transport and endothelial cell biology we observe as a function of the hemodynamic environment. For example we have documented that the exposure of canine carotids to 'hypertensive' (vs 'normotensive') hemodynamics is associated with an increased flux of lipoproteins (LDL) into the intima and luminal media. Alternations in wall compliance, on the other hand, profoundly influence endothelial shape, orientation and cytoskeletal array.     

Effect of acute ischaemia on active and passive large deformation mechanics of canine carotid arteries

Large deformation mechanical properties of dog carotid arteries excised following 1 hour of ischaemia and 1 hour of reperfusion were compared to those of contralaterial normal arteries in vitro. Vascular smooth muscle was invariably activated by 0.5 microgram/ml noradrenaline. Relative reduction in the diameter of postischaemia arteries following noradrenaline administration was twice as large (max.: 13.2 +/- 2.0%) as that of normal controls (max.: 5.7 +/- 1.5%) in the pressure range of 0--220 mmHg. If the smooth muscle was totally relaxed there were no differences between the geometrical (wall-thickness, radius) and mechanical properties (stress, incremental elastic modulus, incremental distensibility, strain-energy density) of the arteries in the two series. It is concluded that the increased reactivity of postischaemic arteries is not caused by changes in geometric or mechanical properties of their passive wall elements.     

Effect of variations in pressure and flow on the geometry of isolated canine carotid arteries

A study is described in which the effects of hemodynamics on arterial geometry are investigated in vitro. A novel perfusion apparatus is employed to deliver pulsatile flow through excised canine carotid arteries under carefully controlled conditions. Data of perfused vessel diameter and arterial wall thickness are derived from the radial displacement of the pulsating vessel as measured using a scanning laser micrometer whose accuracy is determined to be 0.0125 mm (0.0005 in). The results of 30 perfusion experiments suggest that the hemodynamic variables of transmural pressure, pulse pressure and flow rate influence vessel size and radial strain. The physiologic implications of these findings are discussed.     

Analysis of the passive mechanical properties of rat carotid arteries

The passive mechanical properties of rat carotid arteries were studied in vitro. Using a tensile testing machine and a piston pump, intact segments of carotid arteries were subjected to large deformations both in the longitudinal and circumferential directions. Internal pressure, external diameter, length and longitudinal force were measured during the experiment and compared with the in vivo dimensions of the segments prior to excision. The anisotropic mechanical properties of the vessel wall material were analyzed using incremental elastic moduli and incremental Poisson's ratios. The results suggest that there is a characteristic deformation pattern common to all vessels investigated which is highly correlated with the conditions of loading that occur in vivo. That is, under average physiological deformation of the vessel, the longitudinal force is nearly independent of internal pressure. In this range of loading the circumferential incremental elastic modulus is nearly independent of longitudinal strain. However, the longitudinal and radial incremental elastic moduli vary significantly with deformation in this direction. The values of the moduli in all three directions increase with raising internal pressure. The weak coupling between circumferential and longitudinal direction in the wall material of carotid arteries is shown by the small value of the corresponding incremental Poisson's ratios.     

Innervation of the human internal carotid arteries under normal conditions and in stenosis]

The neurohistological investigation of a portion of the internal carotid artery removed in operation on the occasion of occlusion revealed afferent, cholinergic and adrenergic nerve elements randomly located in the examined area. The histochemical and electronmicroscopic investigation of the superior cervical sympathetic ganglion removed from 42 patient operated on the occasion of occlusion of the carotid artery revealed a depletion in the ganglia of synaptic active zones, focal absence of catecholamines and neurohistological materials suggests that a substantial role in the process of stenosing of vascular walls is played by sophisticated effects of innervation connections upon the vessel sheaths.     

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.     

Localization of atherosclerotic lesions in the curving sites of human internal carotid arteries

We studied the distribution of the early atherosclerotic lesions in the curving sites of the human internal carotid arteries composed of the carotid siphon portion (part I) and carotid canal portion (part II). These early atherosclerotic lesions included a localized cloudy thickening with pallor, slight elevation, a non-fibrotic lesion and gray-white or yellowish-white, firm, elevated fibrous plaques. These lesions had the same pattern-distribution in each curving artery. Both were located in the distal regions from the middle of the inner curvature of parts I and II, where eddying fluid motions and directional change in the wall shear stress were considered to occur. In part I, there was a localized cloudy thickening in the younger subjects (average age: 22.8 years) rather than fibrous plaques (average age: 63.3 years). A positive correlation between the extent of the surface areas involved with fibrous plaques and the age of subjects was found in parts I and II. The extent of the surface areas involved with fibrous plaques was significantly greater in part I (26.9%) than in part II (7.85%). The radius of curvature was shorter in the former than in the latter. These results suggest that hemodynamic factors associated with flow in the curving sites of arteries may be important for the localization and progression of atherosclerotic lesions.