Mechanical behaviour and rupture of normal and pathological human ascending aortic wall.

The mechanical properties of aortic wall, both healthy and pathological, are needed in order to develop and improve diagnostic and interventional criteria, and for the development of mechanical models to assess arterial integrity. This study focuses on the mechanical behaviour and rupture conditions of the human ascending aorta and its relationship with age and pathologies. Fresh ascending aortic specimens harvested from 23 healthy donors, 12 patients with bicuspid aortic valve (BAV) and 14 with aneurysm were tensile-tested in vitro under physiological conditions. Tensile strength, stretch at failure and elbow stress were measured. The obtained results showed that age causes a major reduction in the mechanical parameters of healthy ascending aortic tissue, and that no significant differences are found between the mechanical strength of aneurysmal or BAV aortic specimens and the corresponding age-matched control group. The physiological level of the stress in the circumferential direction was also computed to assess the physiological operation range of healthy and diseased ascending aortas. The mean physiological wall stress acting on pathologic aortas was found to be far from rupture, with factors of safety (defined as the ratio of tensile strength to the mean wall stress) larger than six. In contrast, the physiological operation of pathologic vessels lays in the stiff part of the response curve, losing part of its function of damping the pressure waves from the heart.

Response of human coronary arteries at different mechanical conditions.

The lack of reliable mechanical data on coronary arteries hampers the application of numerical models to vascular problems, and precludes physicians from knowing in advance the response of coronary arteries to the different interventions. In this work, the mechanical properties of human coronary arteries have been characterized. Whole samples from human right (RC) and left anterior descending (LAD) coronary arteries aged between 23 and 83 years have been studied by means of in-vitro tensile testing up to failure. Knowledge of the mechanical response of human coronary arteries could be applied to optimize the election of vascular grafts or to prevent arterial damage during angioplasty.

Mechanical properties of human coronary arteries.

The lack of reliable mechanical data on coronary arteries and, more specifically, on their wall strength hampers the application of numerical models and simulations to vascular problems, and precludes physicians from knowing in advance the response of coronary arteries to the different interventions. Studies of the mechanical properties of coronary arteries have been carried out almost exclusively on animals. Only a few studies have tried to characterize the in vivo behavior of human coronaries through tests under physiological conditions. In this work, the mechanical properties of human coronary arteries have been characterized. Whole samples from human right (RC) and left anterior descending (LAD) coronary arteries aged between 23 and 83 years have been studied by means of in-vitro tensile testing up to failure.

Association between mechanics and structure in arteries and veins: theoretical approach to vascular graft confection.

Biomechanical and functional properties of tissue engineered vascular grafts must be similar to those observed in native vessels. This supposes a complete mechanical and structural characterization of the blood vessels. To this end, static and dynamic mechanical tests performed in the sheep thoracic and abdominal aorta and the cava vein were contrasted with histological quantification of their main constituents: elastin, collagen and muscle cells. Our results demonstrate that in order to obtain adequate engineered vascular grafts, the absolute amount of collagen fibers, the collagen/elastin ratio, the amount of muscle cells and the muscle cells/elastic fibers ratio are necessary to be determined in order to ensure adequate elastic modulus capable of resisting high stretches, an adequate elastic modulus at low and normal stretch values, the correct viscous energy dissipation, and a good dissipation factor and buffering function, respectively.

Effect of atherosclerosis on thermo-mechanical properties of arterial wall and its repercussion on plaque instability.

Data from the literature report febrile reactions prior to myocardial infarction in patients with normal coronary arteries and that coronary syndromes seem to be triggered by bacterial and viral infections, being fever the common symptom. The thermo-mechanical behavior of thoracic aortas of New Zealand White rabbits with different degrees of atherosclerosis was measured by means of pressure-diameter tests at different temperatures. Specific measurements of the thermal dilatation coefficient of atheroma plaques were performed by means of tensile tests. Results show a different thermo-mechanical behavior, the dilatation coefficient of atheroma plaque being at least twice that of the arterial wall. Temperature-induced mechanical stress at the plaque-vessel interface could be enough to promote plaque rupture. Therefore, increases of corporal temperature, either local or systemic, can play a role in increasing the risk of acute coronary syndromes and deserve a more comprehensive study.

Arterial complex elastic modulus was preserved after an intercontinental cryoconserved exchange.

There is a pressing need to obtain adequate vascular substitutes for arterial by-pass or reconstruction. Since the performance of venous and commercially prosthetic grafts is not ideal and the availability of autologous arteries is limited, the use of cryopreserved arteries has emerged as a very attractive alternative. In this sense, the development of an inter-continental network for cryopreserved tissue exchange would improve international cooperation increasing the possibilities of obtaining the requested materials. In this work, the effects of an inter-continental shipment, which includes cryopreservation, on the biomechanical properties of sheep aortas were evaluated by means of the arterial complex elastic modulus. It is shown that these properties were preserved after the shipment. The actual possibilities of establishing a network for arterial exchange for the international cooperation are discussed.

Thermomechanical behavior of human carotid arteries in the passive state.

Localized heating or cooling is expanding the clinical procedures used to treat cardiovascular diseases. Advantageous implementation and development of these methods are linked indissolubly to a deeper understanding of the arterial response to combined mechanical and thermal loads. Despite this, the basic thermomechanical behavior of human blood vessels still remains largely unknown, primarily due to the lack of appropriate experimental data. In this work, the influence of temperature on the passive behavior of human carotid arteries was studied in vitro by means of inflation tests. Eleven carotid segments were tested in the range 0-200 mmHg at four different temperatures of 17, 27, 37, and 42 degrees C. The results show that the combined change of temperature and stress has a dramatic effect on the dilatation coefficient of the arterial wall, which is shifted from negative to positive depending on the stress state, whereas the structural stiffness of the arterial wall does not change appreciably in the range of temperatures tested.

Human ERK1 induces filamentous growth and cell wall remodeling pathways in Saccharomyces cerevisiae.

Expression of an activated extracellular signal-regulated kinase 1 (ERK1) construct in yeast cells was used to examine the conservation of function among mitogen-activated protein (MAP) kinases. Sequence alignment of the human MAP kinase ERK1 with all Saccharomyces cerevisiae kinases reveals a particularly strong kinship with Kss1p (invasive growth promoting MAP kinase), Fus3p (pheromone response MAP/ERK kinase), and Mpk1p (cell wall remodeling MAP kinase). A fusion protein of constitutively active human MAP/ERK kinase 1 (MEK) and human ERK1 was introduced under regulated expression into yeast cells. The fusion protein (MEK/ERK) induced a filamentation response element promoter and led to a growth retardation effect concomitant with a morphological change resulting in elongated cells, bipolar budding, and multicell chains. Induction of filamentous growth was also observed for diploid cells following MEK/ERK expression in liquid culture. Neither haploids nor diploids, however, showed marked penetration of agar medium. These effects could be triggered by either moderate MEK/ERK expression at 37 degrees C or by high level MEK/ERK expression at 30 degrees C. The combination of high level MEK/ERK expression and 37 degrees C resulted in cell death. The deleterious effects of MEK/ERK expression and high temperature were significantly mitigated by 1 m sorbitol, which also enhanced the filamentous phenotype. MEK/ERK was able to constitutively activate a cell wall maintenance reporter gene, suggesting misregulation of this pathway. In contrast, MEK/ERK effectively blocked expression from a pheromone-responsive element promoter and inhibited mating. These results are consistent with MEK/ERK promoting filamentous growth and altering the cell wall through its ability to partially mimic Kss1p and stimulate a pathway normally controlled by Mpk1p, while appearing to inhibit the normal functioning of the structurally related yeast MAP kinase Fus3p.

Identification of inhibitor specificity determinants in a mammalian phosphodiesterase.

Mammalian phosphodiesterase types 3 and 4 (PDE3 and PDE4) hydrolyze cAMP and are essential for the regulation of this intracellular second messenger in many cell types. Whereas these enzymes share structural and biochemical similarities, each can be distinguished by its sensitivity to isozyme-specific inhibitors. By using a series of chimeric enzymes, we have localized the region of PDE4 that confers sensitivity to selective inhibitors. This inhibitor specificity domain lies within a short sequence at the carboxyl terminus of the catalytic domain of the protein, consistent with the competitive nature of inhibition by these compounds. Surprisingly, the identified region also includes some of the most highly conserved residues among PDE isoforms. A yeast-based expression system was used for the isolation and characterization of mutations within this area that confer resistance to the PDE4-specific inhibitor rolipram. Analysis of these mutants indicated that both conserved and unique residues are required for isoform-specific inhibitor sensitivity. In some cases, combined point mutations contribute synergistically to the reduction of sensitivity (suppression of IC50). We also report that several mutations display differential sensitivity changes with respect to distinct structural classes of inhibitors.

Yeast model system for study of mammalian phosphodiesterases.

Facile manipulation and rapid regeneration have helped to establish the yeast Saccharomyces cerevisiae as a genetic workhorse. More recently, these simple eukaryotes have been used for the biochemical analysis of mammalian proteins. This article describes the use of a yeast expression system for both in vitro and in vivo assays of mammalian phosphodiesterase (PDE) activity using yeast cells devoid of endogenous PDEs. It also presents simple methodologies for the analysis of the pharmacological properties of mammalian PDEs and describes the use of a powerful genetic selection for mutant forms of PDEs with altered biochemical and pharmacological characteristics.

Use of spirometry to predict risk of pneumothorax in CT-guided needle biopsy of the lung.

OBJECTIVE: Our goal was to assess the usefulness of spirometry to estimate the risk of pneumothorax in patients undergoing percutaneous needle biopsy with CT guidance for solitary pulmonary nodule (SPN). MATERIALS AND METHODS: We studied the results of 51 consecutive percutaneous needle biopsies with CT guidance for SPN obtained between 1988 and 1990. Forty-five men and six women, aged 65 +/- 11 (36-86) years, were included in the study. All biopsies were performed under CT guidance, with 90 mm 25G needles (0.5 mm thickness) fitted into luer-type syringes. The number of needle pass attempts never exceeded three. A spirometry before biopsy was performed in all patients. RESULTS: Pneumothorax occurred in only 10 cases (19%). The patients with pneumothorax showed lower lesion size, forced vital capacity (FVC), forced expiratory volume (FEV1), and FEV1/FVC ratio. The contribution of these factors to pneumothorax was analyzed by a logistic regression model. The FEV1 was most strongly associated with the incidence of pneumothorax. We developed an equation for predicting the risk of this complication. CONCLUSION: We conclude that decreasing FEV1 is associated with a higher pneumothorax rate.

Structural and thermotropic properties of synthetic C16:0 (palmitoyl) ceramide: effect of hydration.

Differential scanning calorimetry (DSC) and X-ray diffraction techniques have been used to investigate the structure and thermotropic properties of synthetic, non-hydroxy fatty acid (16:0) ceramide (NFA(C16)CER) as a function of hydration. Anhydrous NFA(C16)CER shows a single, broad endothermic transition at 95.4 degrees C (delta H = 10.4 kcal/mol). On hydration, a broad exothermic transition appears at approximately 50-70 degrees C while the main endothermic transition decreases to 90.0 degrees C (delta H = 13.8 kcal/mol). The enthalpy of the exothermic transition increases with hydration to a maximum value, delta H = 4.8 kcal/mol. This polymorphic phase behavior depends on the low temperature incubation time and prior cooling rate. X-ray diffraction of fully hydrated NFA(C16)CER at 26 degrees C, shows a well-ordered lamellar phase with a bilayer periodicity d = 46.9 A. At 68 degrees C, above the first exothermic transition, X-ray diffraction shows again a lamellar phase with reduced bilayer periodicity d = 41.8 A and an increased number of both lamellar and wide-angle reflections indicative of enhanced layer and chain packing order, respectively. At 90.0 degrees C, above the main transition, the diffraction pattern shows a broad, intense reflection at 29.9 A and a diffuse reflection at 4.6 A, indicative of a melted chain phase. On cooling, NFA(C16)CER exhibits polymorphic phase behavior involving the conversion of the melted chain phase to a metastable bilayer phase. On heating, this metastable phase undergoes an exothermic transition to a stable bilayer phase; on further heating, NFA(C16)CER converts endothermically to the melted-chain phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Physical properties of ceramides: effect of fatty acid hydroxylation.

The structural and thermotropic properties of alpha-hydroxy fatty acid (HFA) and non-hydroxy fatty acid (NFA) ceramides (CER) have been studied using differential scanning calorimetry (DSC) and X-ray diffraction techniques. The DSC of anhydrous HFA-CER shows a single, sharp reversible transition at 95.6 degrees C (delta H = 15.3 kcal/mol). At intermediate hydrations HFA-CER exhibited more complex behavior but at maximum hydration only a single reversible transition is observed at 80.0 degrees C (delta H = 8.5 kcal/mol). X-ray diffraction of hydrated (74% water) HFA-CER at 20 degrees C shows a lamellar structure with a bilayer periodicity d = 60.7 Angstrum; a single wide angle reflection at 4.2 Angstrum is characteristic of hexagonal chain packing. Above the main transition temperature at 91 degrees C, a hexagonal (HII) phase is observed. In contrast, DSC of anhydrous NFA-CER demonstrates two thermal transitions at 81.3 degrees C (delta H = 6.8 kcal/mol) and 85.9 degrees C (delta H = 3.5 kcal/mol). With increasing hydration, both transitions shift towards lower temperatures; at maximum hydration, on heating, the endothermic transitions occur at 72.7 degrees C (delta H = 9.8 kcal/mol) and 81.1 degrees C (delta H = 4.0 kcal/mol). On cooling, there is hysteresis of both transitions. X-ray diffraction of NFA-CER (80% water) at 20 degrees C shows a well-ordered lamellar structure with a bilayer periodicity d = 58.6 Angstrum and three wide-angle reflections at 4.6 Angstrum, 4.2 Angstrum, and 3.8 Angstrum. At 77 degrees C (between the two transitions), again a lamellar structure exists with reduced bilayer periodicity d = 53.1 Angstrum and four wide-angle reflections at 4.6 Angstrum, 4.2 Angstrum, and 3.8 Angstrum are observed. Above the second transition, only a single low angle reflection at 30.0 Angstrum is observed; a diffuse reflection at 4.6 Angstrum is indicative of a melted chain phase. Thus, HFA-CER exhibits a simple phase behavior involving the reversible conversion of a gel phase to a hexagonal phase (L beta-->HII). However, NFA-CER shows a more complex polymorphic phase behavior involving two gel phases.