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Ethiopathogenesis, diagnosis and prevention of vascular calcification in end stage renal disease.

Extensive atherosclerosis and heavy vascular and valvular calcifications are common complications of end stage renal disease (ESRD) and are very likely related to the high incidence of cardiovascular disease in these patients. The greatly increased incidence of cardiovascular disease is only partly explained by traditional risk factors for atherosclerosis. In ESRD, vascular calcification occurs both in the vascular intima layer and in the tunica media. Intimal calcification is disseminated and is characteristically associated with damaged and abnormally functioning endothelium, and macrophage and vascular smooth muscle cell (VSMC) infiltration typical of atherosclerosis. On the contrary, medial calcification occurs in patchy distribution and the most frequent cell types found in its vicinity are the VSMC and macrophage. The uremic state is associated with numerous metabolic abnormalities and endocrine disturbances primarily involving calcium and phosphorus metabolism. Furthermore, chronic kidney disease and dialysis are considered states of active and strong inflammatory response. These dysfunctions occur early in the course of renal failure and likely contribute to the development and progression of vascular calcification and atherosclerosis. For many years, vascular calcification was considered solely the result of a passive deposition of hydroxyapatite crystals in the arterial wall due to elevated calcium-phosphate ion product. However, a large body of evidence has now shown that this is a highly regulated process governed by factors that closely resemble calcium deposition in bone tissue. In fact, vascular calcification requires changes in the phenotype of VSMC and the expression of several proteins normally involved in bone metabolism. This review is centered on the etiopathogenesis of vascular calcification in ESRD, its detection with modern imaging modalities and the therapeutic approaches currently available to slow its progression.

Calcinosis↗

The radiographic distinction between pericardial and myocardial calcifications.

Calcification overlying the left side of the heart on a chest radiograph may involve either the pericardium or, alternatively, the myocardium in association with a left ventricular aneurysm. Distinction between these two conditions can be of great clinical significance. To identify distinguishing features, we reviewed the radiographs and medical records of 29 patients: 14 had proven calcific pericarditis and 15 had proven calcified left ventricular aneurysm. Pericardial calcification was found primarily over the right-sided cardiac chambers (14 of 14 patients) and in the atrioventricular grooves (11 of 14), infrequently over the base of the left ventricle (five of 14), and rarely over the apex of the left ventricle (two of 14). When the left ventricle was involved, there was always more extensive calcification elsewhere in the pericardium. Myocardial calcification occurred predominantly in the apex of the left ventricle (13 of 15 patients), although it was rarely confined to the posterior wall of the left ventricle (two of 15). By noting characteristic sites of calcium deposition, pericardial calcification can be effectively distinguished from myocardial calcification. Isolated calcification in the region of the left ventricular apex, therefore, strongly suggests left ventricular aneurysm.

Adolescent↗

Ductal carcinoma in situ of the breast: correlation between mammographic calcification and tumor subtype.

OBJECTIVE: Histologic subtypes of ductal carcinoma in situ of the breast have been correlated with disease progression after local excision only. This study was undertaken to determine how the predominant type of calcification seen on mammography correlates with the predominant histologic tumor subtype, knowledge that could aid in the development of clinical criteria for selecting patients for appropriate local treatment. MATERIALS AND METHODS: A prospective double-blind study was performed to correlate the mammographic and histologic findings in 66 consecutive cases of ductal carcinoma in situ, or ductal carcinoma in situ associated with small invasive foci (n = 11), in which microcalcifications seen on mammograms were found in the ductal carcinoma during histologic evaluation of excisional biopsy specimens. Microcalcifications were categorized as predominantly linear or granular and were correlated with the predominant histologic subtype of ductal carcinoma in situ in the tissue containing the calcifications seen on mammograms. RESULTS: Predominantly linear calcifications were present in 47% (18/38) of ductal comedocarcinomas in situ compared with 18% (5/28) of cribriform, solid, or papillary subtypes (p = .01). Predominantly granular calcifications were present in 53% (20/38) of comedocarcinomas compared with 82% (23/28) of the noncomedo types (p = .01). In 94% (16/17) of cribriform ductal carcinomas in situ, granular microcalcifications were seen on mammograms. Seventy-eight percent (18/23) of linear calcifications in ductal carcinoma in situ were associated with the comedo subtype, whereas 53% (23/43) of the granular calcifications were associated with noncomedo subtypes. CONCLUSION: We conclude that the comedo subtype of ductal carcinoma in situ is more likely to be accompanied by linear calcifications than are the noncomedo subtypes, and noncomedo ductal carcinoma in situ is more likely to be associated with granular calcifications than is the comedo subtype when microcalcifications are seen on mammograms. However, there is considerable overlap, and the predominant histologic subtype cannot be predicted on the basis of the microcalcification type with a high degree of accuracy.

Adult↗

Effects of ambient light and view box luminance on the detection of calcifications in mammography.

OBJECTIVE: Viewing conditions can affect diagnostic performance differently depending on background optical densities. We quantified detection accuracy when viewing calcifications in glandular tissue under recommended viewing conditions versus accuracy with lower view box luminance and higher ambient lighting. MATERIALS AND METHODS: A phantom with adipose, 50% adipose and 50% glandular, and glandular-simulating material was imaged, and images were interpreted by five medical imaging physicists using two lighting conditions: the recommended one, high view box luminance (4365 nits) with low ambient light (25 lx), and a suboptimal one, low view box luminance (1763 nits) with moderate ambient lighting (290 lx). Then, a dense (Breast Imaging Reporting and Data System breast composition pattern type 4) unfixed cadaveric breast with numerous native calcifications was imaged 28 times. Nineteen of the films had added clusters of simulated calcifications. Three radiology fellows, each with 11 months of training in mammography, identified the added calcification clusters in the images under the two lighting conditions. Changes in phantom analysis and accuracy of the clinical diagnosis were compared for each lighting condition. RESULTS: On mammograms of the phantom, both speck and fibril identification were degraded by an average of 1.4 objects for the adipose-simulating section (with its darker optical density). For medium optical densities, found in the section with the simulation of 50% glandular and 50% adipose tissue, suboptimal lighting conditions had little or no effect on speck and fibril identification. For sections of the phantom that simulated glandular tissue, an average of 0.6 specks or fibers were not seen when lighting was suboptimal. With the dense cadaveric breast, the fraction of added calcification clusters detected by the three observers improved by an average of 17% when low luminance viewers and high ambient light were replaced with recommended viewing conditions; individual scores of the observers improved significantly: p values ranged from .02 to .05. CONCLUSION: Luminance of the view box and ambient lighting significantly affect detection of calcifications in dense breasts when images are interpreted by radiologists with about 1 year of training in mammography. Detection of calcifications in phantoms is primarily degraded for adipose tissue with its darker optical density. However, when lighting conditions are suboptimal, some observers also have trouble detecting calcifications in glandular tissue with its low optical density.

Adipose Tissue↗

The relationship between ECT nonresponsiveness and calcification of the pineal gland in bipolar patients.

It has been suggested recently that the therapeutic effects of electroconvulsive therapy (ECT) may be mediated in part through stimulation of pineal melatonin secretion. If melatonin does mediate the antidepressant effects of ECT and depression itself is associated in some patients with reduced melatonin secretion, patients with reduced melatonin secretion could respond less readily to ECT. There is evidence to suggest an inverse relationship between melatonin secretion and the degree of pineal calcification. Specifically, heavy pineal calcifications in animals have been reported to be associated with reduced plasma melatonin levels. In this study, an investigation was conducted to establish more precisely the relationship between the clinical response to ECT in 17 bipolar patients and the degrees of pineal calcification present on CT scan. There was a significant association between ECT nonresponsiveness and the presence of pathologically enlarged pineal calcification (i.e., greater than 1 cm in diameter) (p.01). In addition, there was a significant difference in ECT responsiveness in patients without pineal calcification compared to those with pathologically enlarged pineal calcification (F = 6.10; p = .01, one-way ANOVA). These findings indicate an association between enlarged pineal calcification and ECT nonresponsiveness and suggest that reduced melatonin secretion may be associated with ECT nonresponsiveness. An enlarged pineal calcification could be a useful radiological marker of ECT nonresponsiveness and administration of melatonin precursors (i.e., L-tryptophan; 5-HTP) and its cofactors (i.e., pyridoxine, folate) as well as melatonin-release enhancing agents (i.e., 5-methoxypsoralen) prior to ECT might augment its antidepressant effects in bipolar patients.

Adult↗

Electron beam computed tomography and coronary artery disease: scanning for coronary artery calcification.

OBJECTIVE: To review the association of coronary artery calcification with coronary atherosclerosis and its potential clinical application as detected on electron beam computed tomography (EBCT). DESIGN: A literature review of coronary artery calcification, coronary artery disease, and EBCT is presented, and clinical applications of EBCT are discussed. RESULTS: Recent studies have confirmed that arterial calcification is an active process intimately associated with atherosclerotic plaque evolution. Clinical investigations with use of EBCT have shown that a scan "negative" for coronary calcification is common in patients with normal or near-normal findings on coronary angiography, whereas patients with severe obstructive disease most commonly have "positive" scans--greater amounts of coronary artery calcium are associated with more severe luminal disease. Coronary artery calcium as evaluated on EBCT follows patterns that reflect the development of coronary atheromatous disease as a function of age and gender. Although histologic studies have confirmed that not all atherosclerotic segments have detectable calcification, the area of coronary artery calcification quantified on EBCT has a direct, positive relationship with the histopathologic coronary plaque area. CONCLUSION: The long-held notion of "degenerative" calcification of the coronary arteries with aging is incorrect. Although the incidence of coronary artery calcification increases with patient age, this relationship simply parallels the increased incidence of coronary atherosclerosis with advancing age. Data suggest that EBCT is a highly sensitive and specific test for coronary atherosclerosis and provide a basis for clinical applications when EBCT is viewed as a noninvasive method to estimate human coronary atherosclerotic involvement and "plaque burden."

Adult↗

Genetic determinants of arterial calcification associated with atherosclerosis.

Increasing research interest has focused on arterial calcification in the setting of atherosclerosis. Many features of atherosclerosis-related calcification provide useful clinical information. For example, calcium mineral deposits frequently form in atherosclerotic plaque, and intimal arterial calcification can be used as a surrogate marker for atherosclerosis; also, calcium deposits are readily and noninvasively quantified, which is useful because greater amounts of coronary calcification predict a higher risk of myocardial infarction and death. Several mechanisms leading to calcification associated with atherosclerosis have been proposed; however, no direct testing of proposed mechanisms has yet been reported. Studies in genetically altered animals and in humans have shed light on potential genetic determinants, which in turn could form the basis for a more comprehensive understanding of the factors affecting calcification within plaque and the associated pathobiologic implications. We review proposed molecular and cellular mechanisms of atherosclerosis-associated arterial calcification, summarize genetic influences, and suggest areas in which further investigation is needed. Understanding the molecular and genetic determinants of specific structural plaque components such as calcification can provide a solid foundation for the development of novel therapeutic approaches to favorably alter plaque structure and minimize vulnerability to arterial rupture.

Animals↗

Tropoelastin inhibits vascular calcification via 67-kDa elastin binding protein in cultured bovine aortic smooth muscle cells.

In cases of vascular calcification, the expression of tropoelastin is down-regulated, which most likely decreases elastic fiber formation. However, the function of tropoelastin in vascular calcification remains unknown. We investigated whether tropoelastin affects the induction of vascular calcification. Calcification was induced using inorganic phosphate in cultured bovine aortic smooth muscle cells. The increase in tropoelastin due to the addition of recombinant bovine tropoelastin (ReBTE; 1 or 10 microg/ml) or beta-aminopropionitrile (25 microg/ml) significantly inhibited calcification at day 6, as assessed by the o-cresolphthalein complexone method. The addition of an elastin-derived peptide, VGVAPG peptide (0.1-1,000 nM), inhibited calcification at day 6 in a dose-dependent manner. In addition, these responses of beta-aminopropionitrile, ReBTE, and VGVAPG peptide were confirmed using von Kossa staining. To examine whether ReBTE inhibited calcium deposition via the elastin binding protein, lactose and elastin-specific antibody were used. The combination of lactose (20 mM) or this antibody (50 microg/ml) with ReBTE (10 microg/ml) attenuated the inhibition of calcification. These results suggest that increased tropoelastin inhibits vascular calcification in this model via the interaction between tropoelastin and elastin binding protein.

Animals↗

Angiographic correlation of CT calcification in the carotid siphon.

BACKGROUND AND PURPOSE: Calcification in the coronary arteries has been correlated with significant vessel stenosis. The predictive value of calcification within the carotid siphon has not been characterized; however, stenosis in the carotid siphon is potentially important in determining management of patients with ipsilateral carotid bifurcation stenosis. The purpose of this study was to determine optimal parameters for assessing carotid siphon calcification on head CT scans and to compare the CT findings with angiographic results. METHODS: We performed a retrospective review of patients referred for diagnostic carotid arteriography. Those patients who also had undergone a head CT study at our institution were selected. The CT scans and angiograms of 64 patients (128 vessels) were reviewed. Carotid siphon calcification on CT scans was characterized on brain and bone windows as mild, moderate, or severe. Comparison was then made with angiographic findings. RESULTS: The sensitivity and specificity of CT for depicting greater than 50% angiographic stenosis in the carotid siphon were 86% and 98%, respectively, for bone windows and 100% and 0%, respectively, for brain windows. The positive predictive value (PPV) for a stenosis of greater than 50% as evidenced by severe calcification was 86% on bone windows and 11% on brain windows. The PPV for mild and moderate calcification on bone windows was 2.5% and 0%, respectively. CONCLUSION: Severe CT calcification in the carotid siphon as characterized on bone windows correlates with a carotid siphon stenosis of greater than 50% as determined angiographically. Therefore, the identification of severe calcification offers a potential noninvasive method for identifying stenosis of the carotid siphon. This information may be essential in determining management and prognosis for patients with carotid bifurcation stenosis.

Adolescent↗

Relationship between intrathyroid calcifications and thyroglobulin in endemic goiter.

Intrathyroid calcifications represent a common finding within simple or nodular goiters, but, as far as they can be found also inside papillary and medullary thyroid carcinomas, an ultrasonographic detection of intrathyroid calcifications stands as a different diagnosis problem. We have been looking for the presence of parameters associated with thyroid calcifications in patients affected by simple or nodular goiter, either sporadic or endemic. We studied 284 euthyroid subjects, 250 females, ageing from 24 to 90 years, affected by a simple goiter, in the 9.51% of the cases, and by a nodular goiter in the remaining part. 69.37% of the patients came from an endemic goiter area, while the others were affected by sporadic goiter. We tested fT3, fT4, TSH, hTG, Ab-TG, Ab-TPO and performed an ultrasonography in all the subjects, 57.75% of patients shown intrathyroid calcifications in the 57.75% of them. We applied a multistep discriminant analysis taking for the presence/absence of calcifications as dependent variable and we tried to find which variable, by itself or in combination with others, could foretell its presence. We also created a new variable (TG1) to differentiate normal from supraphysiologic concentrations of hTG (< 60 ng/ml). The variable with the highest significance F originated from endemic goiter area (F = 96.36), followed by TG1 (F = 24.46) and age (F = 10.61). On the contrary hTG did not relate to calcifications, due to non-proportionally direct relationship between these two parameters, afterwards we used the multistep logistic regression that gave overlapping significances. This means that supraphysiologic hTG rates are sufficient to predict the possible presence of intrathyroid calcifications. In conclusion, as far as a follicular hyperstimulation can be assumed, especially if long-lasting, the presence of intrathyroid calcifications should rise a clinical suspect toward an old goiter rather than a neoplastic lesion.

Adult↗

Association of osteopontin with calcification in human mitral valves.

BACKGROUND: Little is known about the long-standing inflammation leading to calcification within heart valves. Osteopontin, a phosphorylated glycoprotein, is present within atheromatous calcific plagues in response to vascular endothelial injury. The purpose of the study was to investigate whether osteopontin exists in calcific mitral valve leaflets in human beings, and to determine a link between chronic inflammation leading to mitral stenosis and the osteopontin status of mitral valvular tissue. MATERIALS AND METHODS: We reviewed the case histories of 17 patients who underwent mitral valve replacement therapy for mitral stenosis between 1995 and 1997 (8 men and 9 women, mean age 61 years). Hybrid mouse monoclonal immunoglobulin G1 antibodies were used for immunohistochemical detection of osteopontin in the acetone-fixed specimen. The control group consisted of normal mitral valve tissue from cardiomyopathy patients who underwent cardiac transplantation. RESULTS: A weak osteopontin immunoreactivity was present in apparently normal mitral valve tissue obtained from cardiomyopathy patients. All mitral stenosis patients had immunoreactivity (17/17) for osteopontin within calcific deposits of mitral valve tissue. The intensity of osteopontin activity had a strong association with increasing macrophage and calcium aggregations in the mitral valvular tissue. We found no correlation between osteopontin status and clinical features on the prognosis of calcific mitral stenosis. CONCLUSIONS: We conclude that osteopontin coexists with intimal macrophages in calcific human mitral valve tissue. Demonstration of such association between the presence of osteopontin and calcification in human mitral valves is consistent with the hypothesis that calcification in this tissue is, at least in part, an actively mediated phenomenon.

Aged↗

Calcification of the internal elastic membrane in temporal arteries: its relation to age and gender.

OBJECTIVE: To investigate the age and sex distribution of calcifications of the internal elastic membrane (IEM) in temporal arteries. METHODS: Calcifications of the IEM were assessed light-microscopically in temporal arteries from 40 women and 21 men, aged 51 or more, who were known not to have giant cell arteritis (GCA). Their relation to age and the difference between women and men were tested statistically. RESULTS: The IEM calcifications differed morphologically from the calcifications in Mönckeberg's mediosclerosis and atherosclerosis. They increased significantly with age and were 2.62 times more common in women than men. CONCLUSION: Previous morphological studies indicate that the inflammatory process in GCA is initiated by a foreign-body, giant-cell attack on calcifications of the IEM. The present study showed that IEM calcifications in non-GCA controls show an age and sex distribution similar to that of GCA morbidity. The results may indicate that the presence of IEM calcifications in the general population influences the age and sex distribution of GCA. Furthermore, the findings support the hypothesis that the calcifications, although not disease specific, may play a pathogenetic role in the latter.

Age Factors↗

Thoracic calcifications in childhood.

Thoracic calcifications are found in the following locations: mediastinum, lung, pleura, cardiovascular system, and thoracic wall. The calcifications of the mediastinum include mostly inflammatory lesions and malignant neoplasms. Pulmonary calcifications are mainly inflammatory lesions and metastases of osteosarcomas. Where the cardiovascular system is concerned, the most common calcifications are those of the heart relating to tumors or surgery. Calcifications of the aortic wall and valve calcifications can be found. In the thoracic wall there are calcifications of the bone and of soft tissues. The knowledge of shape and location is very useful for the diagnosis of the underlying disease. Calcifications in the thorax are frequently manifestations of previous infectious processes. Less often, they may be due to neoplasms, metabolic disorders, or previous medical therapy.

Adolescent↗

Vascular calcification in end-stage renal disease.

Vascular calcification is common in patients with end-stage renal disease (ESRD) who are treated with regular dialysis, and it may contribute to the very high mortality rate from cardiovascular causes in such patients. Arterial calcification in those with chronic renal failure can result from the deposition of mineral along the intimal layer of arteries in conjunction with atherosclerotic plaques or from calcium deposition in the medial wall of arteries that is due, at least in part, to disturbances in mineral metabolism. Several reports indicate that coronary artery calcification as measured by electron-beam computed tomography (EBCT) is common and often quite extensive in patients with ESRD, but the clinical significance of this finding remains uncertain. EBCT measurements of coronary artery calcification have been shown to be a useful marker of atherosclerotic burden in the general population, and values serve to predict the risk of adverse cardiovascular events. By contrast, the relationship between coronary artery calcification scores as measured by EBCT and clinically significant coronary artery lesions has not been studied adequately in patients with ESRD. Indeed, calcium accumulation in the coronary arteries and other systemic vessels in patients with chronic renal failure is probably attributable to both intimal and medial wall calcification. Concurrent assessments using coronary angiography and EBCT are needed to determine the diagnostic value of EBCT as a predictor of cardiovascular disease in patients with ESRD. Despite the shortcomings of currently available data, the technique of EBCT makes it possible to detect the presence and to monitor the progression of coronary calcification in those undergoing long-term dialysis. Studies using this non-invasive diagnostic method may provide important new information about factors that initiate the development and mediate the progression of arterial calcification in patients with ESRD.

Calcinosis↗

Inhibition of cusp and aortic wall calcification in ethanol- and aluminum-treated bioprosthetic heart valves in sheep: background, mechanisms, and synergism.

BACKGROUND AND AIM OF THE STUDY: Calcification of bioprosthetic heart valves fabricated from glutaraldehyde (GA)-pretreated heterograft tissue is frequently responsible for the clinical failure of these devices. Stentless bioprostheses fabricated from GA-fixed porcine aortic valves pose an important challenge in this regard, as pathologic calcification can affect not only the bioprosthetic cusps, but also the aortic wall segment. METHODS: A synergistic approach was used to prevent bioprosthetic cusp and aortic wall calcification. Ethanol pretreatment of bioprosthetic heart valves was shown to inhibit cuspal calcification due to multiple mechanisms, including alterations of collagen structure and lipid extraction. AlCl3 pretreatment of bioprostheses to prevent calcification was also investigated; this alters elastin structure, inhibits alkaline phosphatase, and complexes with phosphoesters, thereby inhibiting aortic wall mineralization. RESULTS: Experimental data from rat subdermal implants and sheep mitral replacements showed successful synergism with co-pretreatment of porcine aortic valve bioprostheses with ethanol and AlCl3. Significant inhibition of both cusp and aortic wall calcification was achieved by differential pretreatments that restrict AlCl3 to only the aortic wall, and not the cusp, accompanied by ethanol cuspal exposure. Sequential exposure of bioprostheses, first to AlCl3 and then to ethanol, led to unexpectedly severe cuspal calcification. CONCLUSION: Differential pretreatment of stentless bioprostheses with ethanol and AlCl3 can effectively inhibit both cuspal and aortic wall calcification.

Aluminum↗

[Vascular and tissue calcifications of hemodialysis patients].

The present paper aims to assess radiographic vascular and soft parts calcifications occurrence and its correlation with biochemical profiles. The study was performed in 47 patients (ten diabetic patients), 49 years old, who had been on dialysis for a period of 51 months. Vascular calcifications (VCs) were classified as proximal, distal and soft tissues. In addition, Ca, P, CaxP values in the six months prior to the recruitment period, PTH, FAL and calcium carbonate, calcium acetate, and vitamin D3 intake were determined. A higher frequency of VCs was observed in diabetics, yielding a significant association with proximal 60% (p = 0.05) and almost significant with distal calcifications 70% (p = 0.07). Likewise, a lower CaxP was noted for diabetic VCs in comparison to that seen in non-diabetic VCs (p < 0.05). Proximal and distal VCs in the non-diabetics population were 25% and 20%, respectively; and tissue calcifications were 24%. Age was correlated with proximal and distal VCs (p < 0.01). A higher CaxP was observed in patients with VCs and it yielded an even higher value for tissue calcifications. Lastly, calcium acetate and overall calcium intake was higher in patients with tissue calcifications (p = 0.05). VCs were more frequent in diabetics and they also showed a lower CaxP. VCs in non-diabetics were correlated with CaxP values, whereas tissue calcifications were associated with calcium intake. Therefore, the management of renal osteodystrophy should be changed in order to prevent calcifications as well as to decrease morbidity in hemodialysis patients.

Acetates↗

Integrative measurements of calcifications in stented, antibiotic sterilized and cryopreserved sheep biological valves implanted for one year in tricuspid position.

UNLABELLED: The aim of the study was the characterization of calcification in the leaflets of a cryopreserved and alive heart valve depending on the diagnosed pathologic process. Sheep antibiotic sterilised and cryopreserved biological valves were implanted in tricuspid position in young sheeps for one year period. After this time the valves removed and studied morphologically. The control group consisted of 7 intact valves, the comparative group, so called group of valves after the processing antibiotic sterilization and cryopreservation consisted of 7 valves after mentioned procedures. Histological investigations were based on paraffin sections, calcium deposits were stained von Kossa technique. The measured values included integrative parameters as: 1. area fraction, 2. number of calcifications per area, 3. anisotropy. CONCLUSIONS: 1. A process of initial processing, sterilization and cryopreservation of biological valve increases a number of microcalcifications. 2. Cryopreserved biological valves explanted after one-year implantation into an animal in a tricuspid position possess fine calcifications and calcification foci. A number and size of fine calcifications decreases together with an intensification of degeneration and regressive processes of the connective tissue, especially in hyalinization. Hyalinization of the biological valve tissue seems to be favorable for a valve durability and as a pathological process decreasing calcification. 3. Mathematic analysis of morphometric features defining density and structure of calcifications indicate similarities among cryopreservation and initial processing groups, hyalinization, inflammation, whereas in a group of calcification foci, the similarity can be noticed between inflammation and hyalinization group.

Animals↗

A new model to test the calcification characteristics of bioprosthetic heart valves.

BACKGROUND: Tissue degeneration and calcification are the two chief obstacles to the successful application of bioprosthetic heart valves. To enable the study of the durability of bioprosthetic heart valves and the efficacy of anti-calcification treatment, it has become necessary to develop animal models. The aim of this study is to validate a new model for implantation in the pulmonary position. METHODS: Three juvenile sheep underwent implantation of Carpentier-Edwards pericardial valves in the pulmonary position (experimental group). These three valves were compared with three Carpentier-Edwards pericardial valves in the aortic position in patients which had been explanted due to primary tissue failure (clinical group). The valves were analyzed. RESULTS: The findings of macroscopic, X-ray and light microscopic examination were very similar between the two groups. Scattered irregular calcification was seen near the commissures and at the base of the cusps in both groups. Quantitative calcium content analysis showed that calcification of the cusps had progressed to almost the same degree in both groups (experimental group, 3.7+/-0.2 micro g/mg dry tissue; clinical group, 4.3+/-0.3; p>0.05). In the experimental group, calcification in the commissural area of the cusp was pronounced (6.5+/-1.0). In the clinical group, calcification had also progressed in the commissural area of the cusp (6.0+/-1.5), and extended to the base area of the cusp (6.6+/-1.2). CONCLUSIONS: This model is promising for preclinical evaluation of bioprosthetic heart valves. The degree of calcification is not significantly different between our experimental results after three months of implantation in sheep and clinical results after 10 years of implantation in elderly patients. However, the pattern of calcification is somewhat different between the two groups.

Aged↗