Aortic Wall Specimens Research Articles

Immunohistochemical Abnormalities of Fibrillin in Cardiovascular Tissues in Marfan’s Syndrome

Background. Molecular defects in the glycoprotein fibrillin are believed to be responsible for impaired structural integrity of cardiovascular, skeletal, and ocular tissues in Marfan’s syndrome (MFS). Traditionally, excellent results have been achieved with the Bentall composite graft repair of aneurysms of the ascending aorta in MFS. However, because of the potential complications associated with prosthetic valves, there is growing interest in techniques that preserve the native aortic valve.Methods. Between May 1994 and February 1995, 15 patients with a history of concomitant or remote aortic root aneurysms or dissection underwent operation for valvular heart disease. Specimens of aortic valve, ascending aortic wall, and mitral valve were obtained specifically to observe differences in fibrillin content and architecture between patients with (n = 9) and without (n = 6) MFS. In addition, control specimens of aortic valve, aortic wall, and mitral valve were obtained from 4 patients with isolated valvular or coronary artery disease but no evidence of connective tissue disorders or other aortic pathologic conditions. Fibrillin immunostaining using indirect immunofluorescence was used. Specimens were coded and graded by a blinded observer to determine quantity, homogeneity, and fragmentation of fibrillin.Results. Observed fibrillin abnormalities in MFS and control patients were limited to the midportion (elastin-associated microfibrils) of the aortic valve, aortic wall, and mitral valve tissues. Fibrillin abnormalities of aortic valve, aortic wall, and mitral valve tissues were seen in all patients with MFS and were most severe in those older than 20 years. Similar fibrillin abnormalities of aortic valve and aortic wall specimens were observed in control patients more than 60 years old.Conclusions. Even in the setting of a normal-appearing aortic valve, the current rationale for widespread use of valve-sparing repairs of aortic root aneurysms in patients with MFS and patients older than 60 years should be carefully reexamined in light of these findings.(Ann Thorac Surg 1997;63:1012–17)

Cytokine gene expression in aortic adventitial inflammation associated with advanced atherosclerosis (chronic periaortitis).

To determine whether aortic adventitial chronic inflammation associated with advanced atherosclerosis ("chronic periaortitis") is associated with any detectable cytokine gene expression. RNA was extracted from six fresh surgical specimens of atherosclertic aortic aneurysm wall showing a spectrum of chronic periaortitis. Controls included four normal aortas and an HUT 78 T cell line. Reverse transcriptase and the polymerase chain reaction (PCR) were used to amplify mRNA for interleukins-1 alpha (IL-1 alpha), -2 (IL-2), -4 (IL-4), IL-2 receptor-alpha (IL-2R-alpha), tumour necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma) with beta-actin as an internal control. No TNF-alpha mRNA was detected in any of the inflamed aortic tissue samples, in contrast to the aortic T lymphocytes propagated in culture in IL-2 conditioned medium (aortic cultured T cells) and peripheral blood mononuclear cells from these patients. In contrast, IFN-gamma, IL-1 alpha, IL-2, IL-2 receptor and IL-4 PCR products were detected for each inflamed aortic tissue RNA sample with IFN-gamma mRNA expression increasing with increasing degrees of adventitial inflammation. Only beta-actin mRNA was present in the normal aorta. These findings indicate the active nature of aortic adventitial chronic inflammation associated with human advanced atherosclerosis ("chronic periaortitis") and show its possible progressive potential to the clinically important diseases termed "idiopathic retroperitoneal fibrosis" and "inflammatory aneurysm".

Inflammatory aortic aneurysms: Characteristic appearance on magnetic resonance imaging

Ten to 15% of all aortic aneurysms show inflammatory change. They are characteristically covered on their anterior and lateral sides with thick white fibrous tissue. Peri-aortic fibrosis may spread into the retroperitoneum to encase and obstruct adjacent organs making operative treatment more difficult and increasing the operative morbidity and mortality. Fifteen patients with inflammatory aneurysms and 46 patients with simple non-inflammatory aneurysms were studied prospectively. Each patient underwent magnetic resonance imaging (MRI) using a Picker Vista MR2055 scanner operating at 0.5 tesla. Each scan was reviewed by a radiologist (G.G.H.) preoperatively and a diagnosis of inflammatory or non-inflammatory aneurysm made. At operation, the diagnosis of aneurysm type was made on macroscopic features of inflammatory change, and confirmed histologically using previously published criteria. The radiological diagnosis was found to correspond to the surgical and pathological diagnosis in all cases. In cases of inflammatory aortic aneurysm the aneurysm wall appeared laminated on MRI scan, showing three or more bright, high-signal layers. These appearances of inflammatory change are characteristic, and were present in all 15 patients with such aneurysms. There were no false positives among those patients with simple aneurysms, and no false negatives. Operative specimens of aortic wall were taken from four patients with inflammatory aortic aneurysms and four patients with simple non-inflammatory aortic aneurysms, and subjected to MRI scanning. The characteristic banding appeared only in the inflammatory aneurysm wall samples. Magnetic resonance imaging is a highly sensitive investigative technique for the detection of inflammatory aneurysms, showing characteristic changes. These changes are also seen in in vitro scans of wall samples from inflammatory aneurysms.(ABSTRACT TRUNCATED AT 250 WORDS)

Attenuation measurements in atherosclerotic tissues: problems with phase-cancellation artefacts.

The study was designed to establish whether changes in arterial wall structure due to atherosclerosis may be reflected in the increase of ultrasonic attenuation. Accordingly, fresh aortic wall specimens were analysed by an attenuation technique and pathologically classified into three groups: normal, fibrofatty and calcific. Analysis was performed by using a single broadband transducer acting as transmitter and receiver of the echo produced by a specular reflector positioned behind the specimen under study. Two indices were derived from the transfer function H(f) of the specimen: the slope of the best-fit straight line to In |H(f)| and the absolute value of In |H(f)| at 9MHz. The index based on the slope of In |H(f)| is able to distinguish normal wall from atherosclerotic lesions. The absolute value of In |H(f)| is able to differentiate normal, fibrofatty and calcific groups. However, such an index is strongly influenced by specular reflections at water/specimen interfaces. Acquisition of ultrasonic echoes was improved with the use of a small-diameter transducer, which is presumed to reduce distortion in the transfer function due to phase-cancellation effects. According to a statistical test based on the evaluation of the goodness of the straight-line fit to In |H(f)|, the results of the two sets of measurements were compared. The importance of a small-diameter transducer for the further reduction of phase-cancellation artefacts was assessed.

Viruses in the etiology of atherosclerosis.

To examine the possible role of viruses in the etiology of atherosclerosis, we searched for the presence of viral genomes in arterial tissues by in situ hybridization. Because chickens infected with Marek disease virus, a herpesvirus, develop atherosclerotic lesions after infection, we looked for the presence of herpesvirus or parts thereof in human artery wall tissue, particularly in individuals with evidence of atherosclerosis. Herpesvirus probes were used on specimens of aortic wall removed from patients undergoing coronary bypass surgery. Evidence for the presence of herpes simplex viral mRNA was obtained in 13 specimens. Some of the specimens positive for herpes simplex virus appear to represent early stages in atherogenesis. Evidence for the presence of cytomegalovirus or Epstein-Barr viral genome was not observed in any of the specimens examined. We have also shown that herpes simplex virus can infect human fetal smooth muscle cells in culture. There are several ways in which viruses could operate in the pathogenesis of atherosclerosis: They could induce proliferation of artery wall intimal smooth muscle cells via injury or by genomic alterations leading to clonal expansion of intimal smooth muscle cell populations. We suggest that expression of at least a part of the herpesvirus genome in arterial smooth muscle cells may in some cases be instrumental in initiating or maintaining this enhanced cell proliferation. Furthermore, viral agents could explain other puzzling features in the occurrence of atherosclerosis and the attendant heart disease and strokes.

Different degrees of atherosclerosis detected by backscattered ultrasound: an in vitro study on fixed human aortic walls.

The aim of the study was to establish whether ultrasonic backscattered signals may characterize the atherosclerotic process, providing a quantitative assessment of severity. Measurements on aortic specimens were made in vitro by a transducer acting as transmitter and receiver. Two different indices were measured, one based on peak amplitude value (Vmax) and the other on fast Fourier transform (FFT) analysis of ultrasonic reflected signal (IBI). Two hundred fixed aortic wall specimens (50 normal, 50 fatty streaks, 50 fibrofatty, and 50 calcific) were first characterized ultrasonically and then pathologically, both macroscopically (before ultrasonic study) and histologically (after it). Differentiation of normal, fibrofatty and calcific specimens was achieved using Vmax. Values obtained in fatty streaks overlapped with normal wall but significantly differed from values of fibrofatty and calcific subsets. The results with IBI were similar except that the difference between normal and fibrofatty specimens was not statistically significant. Such changes in acoustic behavior of atherosclerotic walls could be due to increased deposition of highly echogenic biological materials, such as collagen, cholesterol crystals (in fibrofatty specimens), and calcium salts (in calcific ones). Therefore, backscattered signals appear to provide in vitro simple parameters indicative of changes in the arterial wall structure due to the atherosclerotic process.