Regional biomechanical characterization of human ascending aortic aneurysms: Microstructure and biaxial mechanical response

: The ascending thoracic aortic aneurysm (ATAA) is a permanent dilatation of the vessel with a high risk of adverse events, and shows heterogeneous properties. To investigate regional differences in the biomechanical properties of ATAAs, tissue samples were collected from 10 patients with tricuspid aortic valve phenotype and specimens from minor, anterior, major, and posterior regions were subjected to multi-ratio planar biaxial extension tests and second-harmonic generation (SHG) imaging. Using the data, parameters of a microstructure-motivated constitutive model were obtained considering fiber dispersion. SHG imaging showed disruptions in the organization of the layers. Structural and material parameters did not differ significantly between regions. The non-symmetric fiber dispersion model proposed by Holzapfel et al. [25] was used to fit the data. The mean angle of collagen fibers was negatively correlated between minor and anterior regions, and the parameter associated with collagen fiber stiffness was positively correlated between minor and major regions. Furthermore, correlations were found between the stiffness of the ground matrix and the mean fiber angle, and between the parameter associated with the collagen fiber stiffness and the out-of-plane dispersion parameter in the posterior and minor regions, respectively. The experimental data collected in this study contribute to the biomechanical data available in the literature on human ATAAs. Region-specific parameters for the constitutive models are fundamental to improve the current risk stratification strategies, which are mainly based on aortic size. Such investigations can facilitate the development of more advanced finite element models capable of capturing the regional heterogeneity of pathological tissues. STATEMENT OF SIGNIFICANCE: Tissue samples of human ascending thoracic aortic aneurysms (ATAA) were collected. Samples from four regions underwent multi-ratio planar biaxial extension tests and second-harmonic generation imaging. Region-specific parameters of a microstructure-motivated model considering fiber dispersion were obtained. Structural and material parameters did not differ significantly between regions, however, the mean fiber angle was negatively correlated between minor and anterior regions, and the parameter associated with collagen fiber stiffness was positively correlated between minor and major regions. Furthermore, correlations were found between the stiffness of the ground matrix and the mean fiber angle, and between the parameter associated with the collagen fiber stiffness and the out-of-plane dispersion parameter in the posterior and minor regions, respectively. This study provides a unique set of mechanical and structural data, supporting the microstructural influence on the tissue response. It may facilitate the development of better finite element models capable of capturing the regional tissue heterogeneity

The Study of the Fixed Dose Combination of Lisinopril with Prolonged Indopamide (FIXLINDA) with Daily Blood Pressure Monitoring and Diuresis in Hypertensive Patients

Аim. To study the efficacy, tolerability and safety of using a fixed dose combination of an ACE inhibitor lisinopril with a prolonged-action diuretic indapamide in patients with degree 1-2 hypertension.Material and methods. Patients (n = 32) with uncontrolled 1-2 degrees hypertension, moderate or high cardiovascular risk, without severe comorbid diseases, who were prescribed a fixed dose combination of lisinopril (5, 10 or 20 mg) and indapamide (1.5 mg) were included in the observational study. All patients had home monitoring of blood pressure and diuresis, as well as assessment of subjective tolerance of treatment and registration of adverse events within 3 months of observation. Assessment of changes in circadian fluctuations in blood pressure and diuresis, the frequency of achieving the target blood pressure at the outpatient stage, as well as the subjective tolerance of treatment and adverse events during a three-month follow-up.Results. Target blood pressure was achieved in 44.5% of patients taking the fixed dose combination of lisinopril 5 mg + prolonged-acting indapamide1.5 mg; 76.9% – in patients taking the combination of lisinopril 10 mg + indapamide 1.5 mg; 78,6% – in patients taking the combination of lisinopril 20 mg + indapamide 1.5 mg. The achieved antihypertensive effect was characterized by daily circadian stability, accompanied by an improvement in the initially impaired day and night diuretic profile (increase in the share of daytime diuresis by 29.6% and 22.3% with a decrease in the share of nighttime diuresis by 35% and 49% when using a combination with lisinopril 5 and 10 mg, respectively). The treatment was well tolerated by patients and did not cause the development of serious adverse events. Reported adverse events (non-intense dry cough, headache, general weakness) were transient and did not require correction or withdrawal of treatment.Conclusion. The fixed dose combination of the ACE inhibitor lisinopril (5, 10 or 20 mg) and the long-acting thiazide-like diuretic indapamide (1.5 mg) had good antihypertensive efficacy with improved circadian blood pressure and diuresis profiles, acceptable tolerance and safety of treatment, as well as a simple choice of doses of the drug components