Velocity profiles in the wake of two prosthetic heart valves using a new cardiovascular simulator

In this paper we present a study of the post valvular flow field on a new cardiovascular simulator including an elastic model of the aortic arch. Transverse and vertical two-dimensional velocity measurements are performed with an ultrasonic velocimeter. Two prosthetic heart valves are tested in the aortic position. The behaviour of the velocity vectors patterns during one pulsatile cycle is one of the most striking features of the flow.     

Histogenesis of the semilunar valves: an immunohistochemical analysis of tenascin and type-I collagen distribution in developing chick heart valves

Summary The development of the semilunar valves takes place in association with septation of the outflow tract in the embryonic heart. Although numerous studies have focused on this process, the causal mechanisms of valvular development remain obscure. This paper reports an immunohistochemical analysis of tenascin and type-I collagen distribution in developing chick heart valves. Tenascin is a glycoprotein that is present on some embryonic extracellular matrices. It plays several significant roles in tissue differentiation, cell growth, and tissue interactions; it is also important for the formation of specific zones of connective tissue that fulfill mechanical functions. Our results show that tenascin is present during valvular morphogenesis and histogenesis, and that its distribution is associated with zones specialized in bearing mechanical loads.     

Can pulsed ultrasound increase tissue damage during ischemia? A study of the effects of ultrasound on infarcted and non-infarcted myocardium in anesthetized pigs

Background

Natural history of paroxysmal atrial fibrillation (AF) is not very well documented. Clinical experience suggests that paroxysmal AF could progress to chronic AF with estimates ranging between 15 and 30% over a period of 1–3 years. We performed an epidemiologic study to elucidate the natural history of paroxysmal AF, this study estimated its incidence in a general practice setting, identified associated factors and analyzed the progression into chronic AF as well as the mortality rate.

Methods

Using the UK General Practice Research Database (GPRD), we identified patients aged 40–89 years with a first-recorded episode of paroxysmal AF during 1996. Risk factors were assessed using 525 incident paroxysmal AF cases confirmed by the general practitioner (GP) and a random sample of controls. We follow-up paroxysmal AF patients and estimated their mortality rate and progression to chronic AF.

Results

The incidence of paroxysmal AF was 1.0 per 1,000 person-years. Major risk factors for paroxysmal AF were age and prior valvular heart disease, ischaemic heart disease, heart failure and hyperthyroidism. During a mean follow-up of 2.7 years, 70 of 418 paroxysmal AF patients with complete information progressed to chronic AF. Risk factors associated with progression were valvular heart disease (OR 2.7, 95% CI 1.2–6.0) and moderate to high alcohol consumption (OR 3.0, 95% CI 1.1–8.0). Paroxysmal AF patients did not carry an increased risk of mortality, compared to an age and sex matched sample of the general population. There was a suggestion of a small increased risk among patients progressing to chronic AF (RR 1.5, 96% CI 0.8–2.9).

Conclusion

Paroxysmal AF is a common arrhythmia in the general practice setting, increasing with age and commonly associated with other heart diseases. It sometimes is the initial presentation and then progress to chronic AF. A history of valvular heart disease and alcohol consumption are associated with this progression.     

Chondromodulin-I maintains cardiac valvular function by preventing angiogenesis

The avascularity of cardiac valves is abrogated in several valvular heart diseases (VHDs). This study investigated the molecular mechanisms underlying valvular avascularity and its correlation with VHD. Chondromodulin-I, an antiangiogenic factor isolated from cartilage, is abundantly expressed in cardiac valves. Gene targeting of chondromodulin-I resulted in enhanced Vegf-A expression, angiogenesis, lipid deposition and calcification in the cardiac valves of aged mice. Echocardiography showed aortic valve thickening, calcification and turbulent flow, indicative of early changes in aortic stenosis. Conditioned medium obtained from cultured valvular interstitial cells strongly inhibited tube formation and mobilization of endothelial cells and induced their apoptosis; these effects were partially inhibited by chondromodulin-I small interfering RNA. In human VHD, including cases associated with infective endocarditis, rheumatic heart disease and atherosclerosis, VEGF-A expression, neovascularization and calcification were observed in areas of chondromodulin-I downregulation. These findings provide evidence that chondromodulin-I has a pivotal role in maintaining valvular normal function by preventing angiogenesis that may lead to VHD.     

LEFT HEART CATHETERIZATION—The Clinical Importance of Findings

Left heart catheterization using the transbronchial route to obtain pressures in the left atrium and left ventricle was used successfully in 29 cases with no mortality or morbidity. It was found to be useful in differentiating between mitral stenosis and mitral insufficiency, as well as determining the amount of aortic stenosis present when there was involvement of the aortic valve. The technique was also helpful in determining which is the predominant lesion when there is a disease of the aortic and mitral valves.In two patients in a series of 29, data obtained by left heart catheterization forestalled operation on the basis of a mistaken diagnosis of mitral stenosis when actually no mitral valvular disease was present. In another eight patients, the predominant lesion was found to be mitral stenosis rather than mitral insufficiency as it was thought to be before catheterization. In two patients, who had only systolic murmurs, catheterization revealed mitral stenosis rather than mitral insufficiency. In four patients who were thought to have mixed valvular disease, left heart catheterization showed only aortic valvular disease.     

Left heart catheterization; the clinical importance of findings

Left heart catheterization using the transbronchial route to obtain pressures in the left atrium and left ventricle was used successfully in 29 cases with no mortality or morbidity. It was found to be useful in differentiating between mitral stenosis and mitral insufficiency, as well as determining the amount of aortic stenosis present when there was involvement of the aortic valve. The technique was also helpful in determining which is the predominant lesion when there is a disease of the aortic and mitral valves. In two patients in a series of 29, data obtained by left heart catheterization forestalled operation on the basis of a mistaken diagnosis of mitral stenosis when actually no mitral valvular disease was present. In another eight patients, the predominant lesion was found to be mitral stenosis rather than mitral insufficiency as it was thought to be before catheterization. In two patients, who had only systolic murmurs, catheterization revealed mitral stenosis rather than mitral insufficiency. In four patients who were thought to have mixed valvular disease, left heart catheterization showed only aortic valvular disease.     

A field of myocardial-endocardial NFAT signaling underlies heart valve morphogenesis

The delicate leaflets that make up vertebrate heart valves are essential for our moment-to-moment existence. Abnormalities of valve formation are the most common serious human congenital defect. Despite their importance, relatively little is known about valve development. We show that the initiation of heart valve morphogenesis in mice requires calcineurin/NFAT to repress VEGF expression in the myocardium underlying the site of prospective valve formation. This repression of VEGF at E9 is essential for endocardial cells to transform into mesenchymal cells. Later, at E11, a second wave of calcineurin/NFAT signaling is required in the endocardium, adjacent to the earlier myocardial site of NFAT action, to direct valvular elongation and refinement. Thus, NFAT signaling functions sequentially from myocardium to endocardium within a valvular morphogenetic field to initiate and perpetuate embryonic valve formation. This mechanism also operates in zebrafish, indicating a conserved role for calcineurin/NFAT signaling in vertebrate heart valve morphogenesis.     

Red Cell Survival after Heterograft Valve Surgery

Intravascular haemolysis was studied in 24 patients three to nine months after calf or pig valve heterografts had been inserted for severe valvular heart disease. No patient had haemolytic anaemia. In five of the 24 patients there was subclinical haemolysis, and in these five the haemolysis appeared to be related to residual aortic regurgitation or to the presence of other foreign material such as a Dacron aortic graft. The extent of postoperative haemolysis in these five patients was comparable to that observed preoperatively in patients with valvular heart disease.The results support the belief that, in contrast to artificial valve prostheses, heterograft valves behave similarly to human valves as regards haemolysis.     

Second set method for determining the immunogenicity of heart valves

The "second set" method was used on inbred rats to study immunogenicity of the heart valves treated with a proteolytic enzyme and glutaric aldehyde and to compare it with immunogenicity of the valves treated with glutaric aldehyde alone according to Hancock's method. The valves treated by the enzyme and 0.2-0.5% glutaric aldehyde did not lead to the body sensitization in contrast to the valves exposed to 0.5% glutaric aldehyde alone. During transplantation of the latter ones, there were signs of the immunologic response on the part of the recipients and calcification of valvular tissue 70 days after subcutaneous implantation. It is assumed that pretreatment with the enzyme makes it possible to appreciably reduce immunogenicity of the heart valves.     

Partitioning the heart: mechanisms of cardiac septation and valve development

Heart malformations are common congenital defects in humans. Many congenital heart defects involve anomalies in cardiac septation or valve development, and understanding the developmental mechanisms that underlie the formation of cardiac septal and valvular tissues thus has important implications for the diagnosis, prevention and treatment of congenital heart disease. The development of heart septa and valves involves multiple types of progenitor cells that arise either within or outside the heart. Here, we review the morphogenetic events and genetic networks that regulate spatiotemporal interactions between the cells that give rise to septal and valvular tissues and hence partition the heart.     

Histochemical and ultrastructural changes in the extracellular matrix of the developing chick semilunar heart valves.

The present study analyzes the composition and organization of the extracellular matrix (ECM) and its changes in the course of development of the chick embryo semilunar heart valves. In the present work we have employed chick embryos from stage 29 until hatching, using silver and picrosirius red staining, lectin probes and light and transmission electron microscopy. Our results show that during semilunar valve development a series of elements arise and are organized in the ECM which seem to be more closely related to the maintenance of the structural and biomechanical properties of the valvular leaflets than with morphogenetic processes per se.     

The adhering junctions of valvular interstitial cells: molecular composition in fetal and adult hearts and the comings and goings of plakophilin-2 in situ, in cell culture and upon re-association with scaffolds

The interstitial cells of cardiac valves represent one of the most frequent cell types in the mammalian heart. In order to provide a cell and molecular biological basis for the growth of isolated valvular interstitial cells (VICs) in cell culture and for the use in re-implantation surgery we have examined VICs in situ and in culture, in fetal, postnatal and adult hearts, in re-associations with scaffolds of extracellular matrix (ECM) material and decellularized heart valves. In all four mammalian species examined (human, bovine, porcine and ovine), the typical mesenchymal-type cell-cell adherens junctions (AJs) connecting VICs appear as normal N-cadherin based puncta adhaerentia. Their molecular ensemble, however, changes under various growth conditions insofar as plakophilin-2 (Pkp2), known as a major cytoplasmic plaque component of epithelial desmosomes, is recruited to and integrated in the plaques of VIC-AJs as a major component under growth conditions characterized by enhanced proliferation, i.e., in fetal heart valves and in cell cultures. Upon re-seeding onto decellularized heart valves or in stages of growth in association with artificial scaffolds, Pkp2 is - for the most part - lost from the AJs. As Pkp2 has recently also been detected in AJs of cardiac myxomata and diverse other mesenchymal tumors, the demonstrated return to the normal Pkp2-negative state upon re-association with ECM scaffolds and decellularized heart valves may now provide a safe basis for the use of cultured VICs in valve replacement surgery. Even more surprising, this type of transient acquisition of Pkp2 has also been observed in distinct groups of endothelial cells of the endocardium, where it seems to correspond to the cell type ready for endothelial-mesenchymal transition (EMT).     

Essential role for ADAM19 in cardiovascular morphogenesis

Congenital heart disease is the most common form of human birth defects, yet much remains to be learned about its underlying causes. Here we report that mice lacking functional ADAM19 (mnemonic for a disintegrin and metalloprotease 19) exhibit severe defects in cardiac morphogenesis, including a ventricular septal defect (VSD), abnormal formation of the aortic and pulmonic valves, leading to valvular stenosis, and abnormalities of the cardiac vasculature. During mouse development, ADAM19 is highly expressed in the conotruncus and the endocardial cushion, structures that give rise to the affected heart valves and the membranous ventricular septum. ADAM19 is also highly expressed in osteoblast-like cells in the bone, yet it does not appear to be essential for bone growth and skeletal development. Most adam19(-/-) animals die perinatally, likely as a result of their cardiac defects. These findings raise the possibility that mutations in ADAM19 may contribute to human congenital heart valve and septal defects.     

Culturing Mouse Cardiac Valves in the Miniature Tissue Culture System

Heart valve disease is a major burden in the Western world and no effective treatment is available. This is mainly due to a lack of knowledge of the molecular, cellular and mechanical mechanisms underlying the maintenance and/or loss of the valvular structure. Current models used to study valvular biology include in vitro cultures of valvular endothelial and interstitial cells. Although, in vitro culturing models provide both cellular and molecular mechanisms, the mechanisms involved in the 3D-organization of the valve remain unclear. While in vivo models have provided insight into the molecular mechanisms underlying valvular development, insight into adult valvular biology is still elusive. In order to be able to study the regulation of the valvular 3D-organization on tissue, cellular and molecular levels, we have developed the Miniature Tissue Culture System. In this ex vivo flow model the mitral or the aortic valve is cultured in its natural position in the heart. The natural configuration and composition of the leaflet are maintained allowing the most natural response of the valvular cells to stimuli. The valves remain viable and are responsive to changing environmental conditions. This MTCS may provide advantages on studying questions including but not limited to, how does the 3D organization affect valvular biology, what factors affect 3D organization of the valve, and which network of signaling pathways regulates the 3D organization of the valve.     

Atrioventricular valves development in human heart: the Paris embryological collection revisited

29 human embryos staging from stage 15 to stage 23 (post-somitic period, collection of the UER Biomedicale des Saints-Péres, Université René Descartes Paris V) have been studied. The most important morphological events of the atrioventricular valves development have been reinvestigated and photographed. This is a complementary information about cardiac development analysing this french collection of human embryos (Mandarim-de-Lacerda, in press). At stage 15, we can observe the gelatinous reticulum well organized when cardiac valves will become established; progressively the fused endocardial cushions and right and left lateral cushions encircle the atrioventricular channels indicating the site of the tricuspid valves. These cushions, however, have a temporary influence being replaced gradually by atrial and ventricular myocardium. At stage 23, the heart presents a complete atrioventricular valvular structure.     

Correlation between heart valve interstitial cell stiffness and transvalvular pressure: implications for collagen biosynthesis

It has been speculated that heart valve interstitial cells (VICs) maintain valvular tissue homeostasis through regulated extracellular matrix (primarily collagen) biosynthesis. VICs appear to be phenotypically plastic, inasmuch as they transdifferentiate into myofibroblasts during valve development, disease, and remodeling. Under normal physiological conditions, transvalvular pressures (TVPs) on the right and left side of the heart are vastly different. Hence, we hypothesize that higher left-side TVPs impose larger local tissue stress on VICs, which increases their stiffness through cytoskeletal composition, and that this relation affects collagen biosynthesis. To evaluate this hypothesis, isolated ovine VICs from the four heart valves were subjected to micropipette aspiration to assess cellular stiffness, and cytoskeletal composition and collagen biosynthesis were quantified by using the surrogates smooth muscle alpha-actin (SMA) and heat shock protein 47 (HSP47), respectively. VICs from the aortic and mitral valves were significantly stiffer (P < 0.001) than those from the pulmonary and tricuspid valves. Left-side isolated VICs contained significantly more (P < 0.001) SMA and HSP47 than right-side VICs. Mean VIC stiffness correlated well (r = 0.973) with TVP; SMA and HSP47 also correlated well (r = 0.996) with one another. Assays were repeated for VICs in situ, and, as with in vitro results, left-side VIC protein levels were significantly greater (P < 0.05). These findings suggest that VICs respond to local tissue stress by altering cellular stiffness (through SMA content) and collagen biosynthesis. This functional VIC stress-dependent biosynthetic relation may be crucial in maintaining valvular tissue homeostasis and also prove useful in understanding valvular pathologies.     

Spread of excitation through the heart upon electrical stimulation of the atrioventricular valves]

Experiments were conducted on the isolated hearts of rabbits and dogs. Synchronous recording of the electrical activity of the right auricle, the right ventricle, and tricuspid valve demonstrated the existence of definite functional associations between the auricular, ventricular and valvular depolarization. The spread of excitation in the heart in electrical stimulation of the atrio-ventricular valves was investigated. The impulses from the heterotopic excitation focus localized in these valves could be conducted to the other parts of the heart and thus lead to cardiac arrhythmias.