麻黄碱对兔主动脉和心房作用机制的研究

麻黄碱(E,×10~(-4)—3.3×10~(-3)M)和去甲肾上腺素(NA,6×10~(-8)—6×10~(-5)M)均能引起离体兔主动脉条浓度依赖性收缩。可卡因能明显地增强 NA 的作用,但明显地减弱麻黄碱的作用,用可卡因后麻黄碱的作用为用可卡因前的10—92.6%。利血平处理后,麻黄碱和 NA的作用都明显增强,但利血平对前者的增强作用比后者更甚。在利血平处理及未处理肌条上,麻黄碱的作用均可被酚妥拉明阻断。麻黄碱(3.3×10~(-6)—3.3×10~(-5)M)和异丙肾上腺素(ISP,10~(-9)—10~(-5)M)均能引起离体兔心房率的增加。可卡因明显地减弱麻黄碱的这一作用,即为对照组的8.8—29.1%,但不影响 ISP 的作用。利血平处理后,麻黄碱对兔心房的作用也明显减弱,为对照纽的15.4—28.4%;而 ISP 作用则略增加。3×10~(-4)麻黄碱可明显增加[3~H]NA 从兔主动脉条的流出量,此作用在给药后5min内即开始,可持续30 min 以上。上述结果提示,对于兔主动脉和心房,麻黄碱兼具直接作用于效应器细胞和通过释放末梢中 NA 的间接作用;直接作用在主动脉占优势,间接作用在心房占优势。     

5-羟色胺诱发的主动脉区化学感受性升血压反射中某些区域性血管反应的分析

在15只麻醉开胸犬中,用在体器官恒流灌注法研究了骨胳肌、皮肤、肾和心脏的血管在5-HT 诱发的主动脉区化学感受性升血压反射中的反应,同时还观察了5-HT 对这些器官血管的直接效应。左心房注入5-HT(200μg)后,在动脉血压急剧上升的同时,股薄肌、皮肤(后爪)和肾脏的灌流压明显增加,其增值分别为43±8.47±5和56±27mmHg(P<0.01),而冠脉灌流压无明显改变。用阿托品和/或心得安阻断骨胳肌、皮肤和心脏灌流区域的 m 和同β-受体后,上述效应无进一步变动。向灌流环路直接注入5-HT(10—50μg),可引起皮肤和肾脏的血管收缩,而股薄肌和心肌的血管则扩张;后一效应不被心得安阻断。以上结果提示:1.在5-HT 诱发的主动脉区化学感受性升血压反射中,骨胳肌、皮肤和肾脏呈现明显的交感性缩血管反应,而并不伴有交感性扩血管活动;2.在外周血管可能存在两种不同的5-HT 受体,一种主要分布在皮肤和肾脏,引起缩血管效应;另一种主要分布于骨胳肌和冠状血管,引起扩血管效应。     

Elasto-regenerative properties of polyphenols

Abdominal aortic aneurysms (AAA) are progressive dilatations of infra-renal aorta causing structural weakening rendering the aorta prone to rupture. AAA can be potentially stabilized by inhibiting inflammatory enzymes such as matrix metalloproteinases (MMP); however, active regression of AAA is not possible without new elastic fiber regeneration. Here we report the elastogenic benefit of direct delivery of polyphenols such as pentagalloyl glucose (PGG), epigallocatechin gallate (EGCG), and catechin, to smooth muscle cells obtained either from healthy or from aneurysmal rat aorta. Addition of 10 μg/ml PGG and ECGC induce elastin synthesis, organization, and crosslinking while catechin does not. Our results indicate that polyphenols bind to monomeric tropoelastin and enhance coacervation, aid in crosslinking of elastin by increasing lysyl oxidase (LOX) synthesis, and by blocking MMP-2 activity. Thus, polyphenol treatments leads to increased mature elastin fibers synthesis without increasing the production of intracellular tropoelastin.     

AT2R agonist NP‐6A4 mitigates aortic stiffness and proteolytic activity in mouse model of aneurysm

Clinical and experimental studies show that angiotensin II (AngII) promotes vascular pathology via activation of AngII type 1 receptors (AT1Rs). We recently reported that NP‐6A4, a selective peptide agonist for AngII type 2 receptor (AT2R), exerts protective effects on human vascular cells subjected to serum starvation or doxorubicin exposure. In this study, we investigated whether NP‐6A4–induced AT2R activation could mitigate AngII‐induced abdominal aortic aneurism (AAA) using AngII‐treated Apoe^?/? mice. Male Apoe^?/? mice were infused with AngII (1 µg/kg/min) by implanting osmotic pumps subcutaneously for 28 days. A subset of mice was pre‐treated subcutaneously with NP‐6A4 (2.5 mg/kg/day) or vehicle for 14 days prior to AngII, and treatments were continued for 28 days. NP‐6A4 significantly reduced aortic stiffness of the abdominal aorta induced by AngII as determined by ultrasound functional analyses and histochemical analyses. NP‐6A4 also increased nitric oxide bioavailability in aortic tissues and suppressed AngII‐induced increases in monocyte chemotactic protein‐1, osteopontin and proteolytic activity of the aorta. However, NP‐6A4 did not affect maximal intraluminal aortic diameter or AAA incidences significantly. These data suggest that the effects of AT2R agonist on vascular pathologies are selective, affecting the aortic stiffness and proteolytic activity without affecting the size of AAA.     

Prostatic irradiation-induced sexual dysfunction: A review and multidisciplinary guide to management in the radical radiotherapy era (Part II on Urological Management)

Prostate cancer is the most common malignancy in men and the second leading cause of cancer-related death in men. Radiotherapy is a curative option that is administered via external beam radiation, brachytherapy, or in combination. Sexual dysfunction is a common toxicity following radiotherapy, similar to men undergoing radical prostatectomy, but the etiology is different. The pathophysiology of radiation-induced sexual dysfunction is multi-factorial, and the toxicity is a major cause of impaired quality of life among long-term prostate cancer survivors. Management of a patient’s sexual function during and after radiotherapy requires multidisciplinary coordination of care between radiation oncology, urology, psychiatry, pharmacy, and dermatology. This review provides a framework for clinicians to better understand prostatic radiotherapy-induced sexual dysfunction diagnosis, evaluation, and a patient-centered approach to toxicity preventive strategies and management.     

Hemodynamic investigation of a patient-specific abdominal aortic aneurysm with iliac artery tortuosity

Abstract

This paper describes a systematic investigation on the hemodynamic environment in a patient-specific AAA with tortuous common iliac artery(CIA) and external iliac artery (EIA). 3D reconstructions from CT scans and subsequent computational simulation are carried out. It is found out that the Newtonian and non-Newtonian models have very similar flow field and WSS distribution. More importantly, it is revealed that the torturous CIA maintained its helical flow. It is concluded that the assumption of Newtonian blood is adequate in capturing the intra-aneurysmal hemodynamics. Moreover, it is speculated that the physiological spiral flow protects the twisted CIA from the thrombosis formation.     

Design of a resilient ring for middle ear’s chamber stapes prosthesis

Abstract

This paper presents the process of designing a new elastic element replacing a membrane in the chamber stapes prosthesis (ChSP). The results of the study are volume displacement characteristics obtained for the prosthesis and physiological stapes. Simulation tests on a 3D CAD model have confirmed that a properly designed ring can stimulate perilymph with the same or greater efficacy as the physiological stapes footplate placed on the elastic annular ligament. The ChSP with a new elastic element creates a good chance of improving hearing in patients suffering from otosclerosis.     

Direct numerical simulation of a 2D-stented aortic heart valve at physiological flow rates

We study the nonlinear interaction of an aortic heart valve, composed of hyperelastic corrugated leaflets of finite density attached to a stented vessel under physiological flow conditions. In our numerical simulations, we use a 2D idealised representation of this arrangement. Blood flow is caused by a time-varying pressure gradient that mimics that of the aortic valve and corresponds to a peak Reynolds number equal to 4050. Here, we fully account for the shear-thinning behaviour of the blood and large deformations and contact between the leaflets by solving the momentum and mass balances for blood and leaflets. The mixed finite element/Galerkin method along with linear discontinuous Lagrange multipliers for coupling the fluid and elastic domains is adopted. Moreover, a series of challenging numerical issues such as the finite length of the computational domain and the conditions that should be imposed on its inflow/outflow boundaries, the accurate time integration of the parabolic and hyperbolic momentum equations, the contact between the leaflets and the non-conforming mesh refinement in part of the domain are successfully resolved. Calculations for the velocity and the shear stress fields of the blood reveal that boundary layers appear on both sides of a leaflet. The one along the ventricular side transfers blood with high momentum from the core region of the vessel to the annulus or the sinusoidal expansion, causing the continuous development of flow instabilities. At peak systole, vortices are convected in the flow direction along the annulus of the vessel, whereas during the closure stage of the valve, an extremely large vortex develops in each half of the flow domain.