Dimitrios C. Iliopoulos

Ascending thoracic aortic aneurysms are associated with compositional remodeling and vessel stiffening but not weakening in age-matched subjects

OBJECTIVE We sought to examine in age-matched subjects the biomechanical and compositional remodeling associated with ascending thoracic aortic aneurysms according to region and direction. METHODS Whole, fresh, degenerative ascending thoracic aortic aneurysms were taken from 26 patients (age, 69 +/- 2 years; maximum aortic diameter, 5.9 +/- 0.3 cm) during elective surgical intervention, and 15 nonaneurysmal ascending thoracic aortas were obtained during autopsies (age, 66 +/- 3 years; maximum aortic diameter, 3.3 +/- 0.2 cm). These were cut into anterior, right lateral, posterior, and left lateral regions, and circumferentially and longitudinally oriented specimens were prepared. The aortic specimens were submitted to histomorphometric and biomechanical studies, including measurement of failure strain (ie, extensibility), failure stress (ie, strength), and peak elastic modulus (ie, stiffness). RESULTS Wall elastin, but not collagen content, decreased in aneurysmal specimens, displaying lower wall thickness and failure strain, higher peak elastic modulus, and equal failure stress than control specimens in the majority of regions and directions. Similar differences were noted in pooled data from all regions. Regional variations in mechanical parameters were mostly found in longitudinally oriented tissue. Circumferential specimens showed higher failure stress and peak elastic modulus but equal failure strain than longitudinal specimens. CONCLUSIONS Our findings contradict previous studies on ascending thoracic and abdominal aortic aneurysms, suggesting that the former might not cause weakening but rather only stiffening and reduction in tissue extensibility and elastin content. Marked heterogeneity was evident in healthy and aneurysmal aortas. The present data offer insight into the pathogenesis of aneurysm dissection. Information on directional and regional variations is pertinent because dissections develop circumferentially and bulging preferentially occurs in the anterior region.

Regional and directional variations in the mechanical properties of ascending thoracic aortic aneurysms

This study aimed to assess regional and directional differences in the mechanical properties of ascending thoracic aortic aneurysms (ATAA). Whole fresh ATAA were taken from twelve patients, undergoing elective surgical repair, and cut into tissue specimens. These were divided into groups according to direction and region, and subjected to uniaxial testing beyond rupture. In the majority of tests, the inner layers of the aortic wall ruptured first; failure stress (measure of tissue strength) and peak elastic modulus (measure of tissue stiffness) were significantly higher circumferentially in all regions. Marked heterogeneity was evident in the mechanical properties of ATAA, with the anterior region longitudinally being the weakest and least stiff of all regions. No correlation was found between failure stress and ATAA diameter or patient age. Failure stress showed inverse correlations with wall thickness and direct correlations with peak elastic modulus. The current information, relating to regional and directional differences, may provide a better understanding of the mechanism responsible for the development of circumferential tears of the inner aortic wall layers in ATAA dissections.

Impaired mechanics and matrix metalloproteinases/inhibitors expression in female ascending thoracic aortic aneurysms.

We hypothesized that female gender may have a specific negative impact on the mechanical characteristics, composition, and expression of matrix metalloproteinases/tissue inhibitors (MMPs/TIMPs) in the wall of ascending thoracic aortic aneurysms (ATAAs). Degenerative ATAAs were resected from 35 patients (age: 67±2 years, male: 20, ATAA diameter: 5.5±0.1cm) undergoing elective surgery. Tissue specimens were grouped by gender, region, and direction and submitted to immunohistochemistry for semi-quantitative assessment of MMP-2, MMP-9, TIMP-1, and TIMP-2 expressions, i.e. of staining intensity in extracellular matrix and immunoreactivity in vascular cells, as well as to histology for quantitation of elastin/collagen contents. Biomechanical characterization by the Fung-type model and examination of failure properties was performed. Gender differences in patient age, ATAA diameter, and ATAA diameter/body-surface area were non-significant. Increased MMP-2 and MMP-9, and decreased TIMP-1 and TIMP-2 expressions were observed in females. Elastin/collagen contents were higher in males than females, as was failure stress in circumferential but not longitudinal specimens. In both directions, failure stretch was invariant, while the Fung-type model parameters and elastic moduli calculated at physiologic stress levels were higher in females, suggestive of increased wall stiffness compared to males. MMP and TIMP expressions did not differ with region, unlike failure stress longitudinally that was greater posteriorly than anteriorly. The female gender is associated with impaired ATAA strength and increased stiffness, relating to the more extensive extracellular matrix breakdown and significantly higher ratio of MMP/TIMP expression witnessed in females. The present data may aid to identify the underlying pathophysiology accountable for the higher rupture risk, documented by epidemiologic studies in females.

Effect of statins on serum apolipoprotein j and paraoxonase-1 levels in patients with ischemic heart disease undergoing coronary angiography.

It has been proposed that apolipoprotein J (apo J) and paraoxonase-1 (PON1) correlate with the extent and severity of ischemic heart disease (IHD). This article compares apo J and PON1 serum concentrations, PON1 activity, and the apo J/PON1 ratio in 138 IHD patients (64 statins users and 74 statin nonusers) referred for angiography and possible percutaneous coronary intervention. The effect of statin treatment on apo J and PON1 concentrations, PON1 activity, and the degree of coronary artery stenosis were evaluated. In both groups, apo J levels were increased, whereas PON1 concentration and activity decreased. IHD patients on statins had significantly lower apo J concentration and higher PON1 concentration and activity. Patients on statins had less coronary artery stenosis. High apo J levels, low PON1 levels, low PON1 activity, and a high apo J/PON1 ratio were associated with IHD. Statin treatment reverses these changes, probably by multiple beneficial actions.

Biomechanical properties and histological structure of sinus of Valsalva aneurysms in relation to age and region

Information on the biomechanical properties of aortic root aneurysms that would facilitate our understanding of their rupture modes is currently unavailable. In this study, whole-thickness wall specimens from aortic root aneurysms were studied in vitro so as to compare the biomechanical properties with gross histomorphology and composition, in relation to age, region, and direction. The stress-strain relationship was determined under uniaxial loading conditions and characterized by the Fung-type material model in terms of optimized material constants; failure properties were recorded. The connective tissue contents of the basic scleroproteins were also determined through computerized histology. Aging had a deleterious influence on the tensile strength of the aneurysmal sinus tissue, causing also stiffening and reduced extensibility that was consistent with the deficient elastin and collagen contents. Direction-dependent differences were demonstrated in the noncoronary sinus, with the circumferential being stiffer and stronger than the longitudinal direction, justified by the preferred collagen reinforcement along that direction there. In the left and right coronary sinus, the material constants and failure properties were essentially the same in the two directions, justified by the arbitrary orientation of medial (collagen and elastin fibers, and cellular) components relative to the circumferential-longitudinal directions. The material characterization results afforded, and the regional and age-related differences in the strength of the sinus wall, i.e. in its capacity to withstand hemodynamic stresses, are hoped to provide novel insight into the pathophysiological mechanisms responsible for the highest incidence of ruptured aortic root aneurysms in the right coronary and noncoronary sinus.

Biomechanical Properties of Ascending Thoracic Aortic Aneurysms and Mathematical Characterization

To properly understand the natural history of ascend ing thoracic aortic aneurysms (ATAA) and better assess their risk of rupture, stress analyses asking for biaxial biomechanical data of the tissue are necessary, but information on this matter is restricted in the literature. The present study addressed the role of ATAA on the biomechanical response of vessel wall. Degenera tive ATAA were excised from patients during graft replacement and non-aneurysmal age-matched vessels during autopsy. Uniaxi al tensile-tests were conducted on circumferential (CIRC) and longitudinal (LONG) tissue strips. The experimental recordings were reduced by a Fung-type strain-energy function that was found to be appropriate for characterization of the vessel’s biome chanical response. The material parameters and rupture proper ties disclosed that ATAA and non-aneurysmal aorta were aniso tropic, i.e. stronger and stiffer in the CIRC direction. ATAA had no influence on tissue strength, but caused stiffening and exten sibility reduction. Our findings may serve as input data for the implementation of finite element models to be used as improved surgical intervention criteria.

Chios mastic gum decreases renin levels and ameliorates vascular remodeling in renovascular hypertensive rats

Chios mastic gum (CMG) exerts robust anti-inflammatory and antioxidant properties and it affects pathways that are implicated in the pathophysiology of endothelial and vascular inflammation. Aim of this study was to test the hypothesis that CMG administration lowers blood pressure (BP) and improves hypertension-induced target organ damage. 2-kidney, 1-clip (2K1C) hypertensive rats were treated with CMG (40 mg/kg body weight/day) for 2-weeks after the establishment of hypertension. Acute CMG administration lowered systolic, diastolic and mean arterial BP, while these hemodynamic effects were sustained throughout the 2-week administration period. CMG group also exhibited alleviated target organ damage as proposed by amelioration of biomechanical properties of the aorta -including cross-sectional area (CSA), aortic wall stiffness and thickness-, reversal of myocardial small vessel hypertrophy and maintenance of serum albumin levels. The anti-hypertensive effects of CMG are likely to be mediated by the decrease in renin serum levels. Regression analysis indicated that the effect of CMG on organ damage was BP-lowering dependent and was not associated with direct effects of renin or with its anti-inflammatory properties. We suggest a BP lowering effect of CMG via down-regulation of renin excretion associated with attenuation of target organ damage and inflammatory status. These observations provide profound evidence for the beneficial role of CMG in hypertension, which could possibly translate to further clinical research.

Novel approaches for the treatment of ventricular tachycardia

Ventricular tachycardia (VT) is a crucial cause of sudden cardiac death (SCD) and a primary cause of mortality and morbidity in patients with structural cardiac disease. VT includes clinical disorders varying from benign to life-threatening. Most life-threatening episodes are correlated with coronary artery disease, but the risk of SCD varies in certain populations, with various underlying heart conditions, specific family history, and genetic variants. The targets of VT management are symptom alleviation, improved quality of life, reduced implantable cardioverter defibrillator shocks, prevention of reduction of left ventricular function, reduced risk of SCD, and improved overall survival. Antiarrhythmic drug therapy and endocardial catheter ablation remains the cornerstone of guideline-endorsed VT treatment strategies in patients with structural cardiac abnormalities. Novel strategies such as epicardial ablation, surgical cryoablation, transcoronary alcohol ablation, pre-procedural imaging, and stereotactic ablative radiotherapy are an appealing area of research. In this review, we gathered all recent advances in innovative therapies as well as experimental evidence focusing on different aspects of VT treatment that could be significant for future favorable clinical applications.