Search PubMed⌕ Search

Biomedical subjects

E Bos

Publications and source records attributed to E Bos.

At least 19 recordsLinked to original sources

Decline in ventricular function and clinical condition after Mustard repair for transposition of the great arteries (a prospective study of 22-29 years).

BACKGROUND: Great concern exists about the ability of the anatomic right ventricle to sustain the systemic circulation in patients with transposition of the great arteries who have undergone a Mustard procedure. A prospective study was made to examine long-term survival, clinical outcome, and right ventricular function 25 years after surgery. METHODS: Ninety-one consecutive patients underwent the Mustard procedure between 1973 and 1980. After 14 years and again after 25 years (range 22-29 years), patients were studied with ECG, echocardiography, exercise testing, and Holter monitoring. RESULTS: The cumulative survival and event-free survival were 77% and 36%, respectively, after 25 years. Reoperation was necessary in 46%. No major loss of sinus rhythm was found. While all patients had good right ventricular function 14 years after repair, 61% of patients showed moderate-to-severe dysfunction after 25 years, when studied by echocardiography. Furthermore, the QRS complex widened and exercise capacity decreased. CONCLUSION: The anatomic right ventricle appears to be unable to sustain the systemic circulation at long-term follow-up and the clinical condition of patients late after Mustard repair is declining. We can expect more deaths or need for heart transplantation in the next decade.

Adult↗

Direct visualization of receptor arrays in frozen-hydrated sections and plunge-frozen specimens of E. coli engineered to overproduce the chemotaxis receptor Tsr.

We have recently reported electron tomographic studies of sections obtained from chemically fixed E. coli cells overproducing the 60-kDa chemotaxis receptor Tsr. Membrane extracts from these cells prepared in the presence of Tween-80 display hexagonally close-packed microcrystalline assemblies of Tsr, with a repeating unit large enough to accommodate six Tsr molecules arranged as trimers of receptor dimers. Here, we report the direct visualization of the Tsr receptor clusters in (i) vitrified cell suspensions of cells overproducing Tsr, prepared by rapid plunge-freezing, and (ii) frozen-hydrated sections obtained from cells frozen under high pressure. The frozen-hydrated sections were generated by sectioning at -150 degrees C using a diamond knife with a 25 degrees knife angle, with nominal thicknesses ranging from 20 to 60 nm. There is excellent correspondence between the spatial arrangement of receptors in thin frozen-hydrated sections and the arrangements found in negatively stained membrane extracts and plunge-frozen cells, highlighting the potential of using frozen-hydrated sections for the study of macromolecular assemblies within cells under near-native conditions.

Bacterial Proteins↗

Human tissue valves in aortic position: determinants of reoperation and valve regurgitation.

BACKGROUND: Human tissue valves for aortic valve replacement have a limited durability that is influenced by interrelated determinants. Hierarchical linear modeling was used to analyze the relation between these determinants of durability and valve regurgitation measured by serial echocardiography. METHODS AND RESULTS: In adult patients, 218 cryopreserved aortic allografts were implanted with the subcoronary (85) or the root replacement technique (133), and 81 patients had root replacement with a pulmonary autograft. Mean follow-up was 4.2 years (SD 2.7; range, 0 to 10.5). Patient age, operator experience with subcoronary implantation, and allograft diameter were independent predictors for reoperation. With repeated color Doppler echocardiography, the severity of aortic regurgitation was assessed by the jet length method and the jet diameter ratio. Multilevel hierarchical linear modeling was used to estimate initial aortic regurgitation (intercept), its change over time (slope), and the effect of 11 potential determinants of durability on aortic regurgitation. With the jet length method, the intercept was 0.94 grade and the slope was 0.11 grade per year. With the jet diameter ratio, the intercept was 0.34 and the annual increase was 0.01. Subcoronary implanted valves had more initial aortic regurgitation, but progression of aortic valve regurgitation did not differ from root replacement. At midterm follow-up, recipient age <40 years was the only independent predictor of aortic regurgitation. CONCLUSIONS: Subcoronary implantation has a learning curve, resulting in more initial aortic regurgitation and early reoperation compared with root replacement. In both techniques, progression of aortic regurgitation over time is small but accelerated in young adults.

Adolescent↗

Autoantigenic HCgp39 epitopes are presented by the HLA-DM-dependent presentation pathway in human B cells.

It is hypothesized that autoimmune diseases manifest when tolerance to self-Ags fails. One possible mechanism to break tolerance is presentation of self-Ag in an altered form. Most Ags are presented by APCs via the traditional presentation pathway that includes "epitope editing" by intracellular HLA-DM, a molecule that selects for stable MHC-peptide complexes. We were interested in testing the hypothesis that autoreactive MHC-peptide complexes may reach the cell surface by an alternate pathway without being edited by HLA-DM. We selected a cartilage autoantigen human cartilage glycoprotein 39 to which T cell responses are observed in rheumatoid arthritis (RA) patients and some DR(*)04 healthy subjects. RA is genetically associated with certain DRB1 alleles, including DRB1(*)0401 but closely related allele DRB1(*)0402 is either neutral or mildly protective with respect to RA. We generated human B lymphoblastoid cell line cells expressing DR(*)0401 or DR(*)0402 in the presence or absence of intracellular HLA-DM and assessed their ability to present a candidate autoantigen, human cartilage glycoprotein 39. Our results show that the presence of intracellular HLA-DM is critical for presentation of this autoantigen to CD4(+) T cell hybridomas generated from DR(*)04-transgenic mice. Presentation of an autoantigen by the traditional HLA-DM-dependent pathway has implications for Ag presentation events in RA.

Adipokines↗

Characterization of coated vesicles that participate in endocytic recycling.

While the recycling pathway of endocytosis has been shown to participate in many cellular functions, little is known regarding the transport carriers that mediate this pathway. In this study, we overexpressed a point mutant of ADP-ribosylation factor 6 (ARF6), that perturbs its GTPase cycle, to accumulate endosome-derived coated vesicles. Characterization by their purification revealed that, upon cell homogenization, these vesicles were mostly aggregated with larger noncoated membranes, and could be released with high-salt treatment. Equilibrium centrifugation revealed that these vesicles had buoyant density similar to the COP-coated vesicles. To purify the ARF6-regulated vesicles to homogeneity, enriched fractions from equilibrium centrifugation were subjected to immunoisolation through the hemagglutinin (HA) epitope of the mutant ARF6, by using a newly developed, high-affinity, anti-HA monoclonal antibody. Surface iodination of the purified vesicles revealed multiple prominent proteins. Immunoblotting with antibodies against subunits of the currently known coat proteins suggested that these vesicles have a novel coat complex. These vesicles are carriers for endocytic recycling, because they are enriched for transferrin receptor and also the v-SNARE cellubrevin that functions in transport from the recycling endosome to the plasma membrane. Thus, we have characterized transport vesicles that participate in endocytic recycling.

ADP-Ribosylation Factor 6↗

Human cartilage gp-39+,CD16+ monocytes in peripheral blood and synovium: correlation with joint destruction in rheumatoid arthritis.

OBJECTIVE: To investigate the expression of human cartilage (HC) gp-39, a possible autoantigen in rheumatoid arthritis (RA), in peripheral blood and synovium, to characterize its cellular source, and to analyze correlations with clinical features. METHODS: The expression of HC gp-39 in synovium and peripheral blood mononuclear cells (PBMC) was assessed by immunohistochemistry and flow cytometry. Synthesis and secretion were investigated by both reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: PBMC expressing HC gp-39 were increased in RA patients compared with spondylarthropathy patients (P = 0.0029) and with healthy control subjects (P = 0.0013). HC gp-39+ cells were also slightly overrepresented in RA synovium (P = 0.01). In both blood and synovium, HC gp-39+ cells were identified as CD14dim,CD16+ monocytes, a phenotype which can differentiate from classic CD14++ monocytes by maturation in vitro. HC gp-39 messenger RNA was detected in RA synovium and PBMC, and PBMC secreted HC gp-39 in vitro. The number of HC gp-39+ PBMC correlated with serum levels of C-reactive protein (r = 0.39, P = 0.003) and HC gp-39 (r = 0.52, P = 0.014). HC gp-39 expression in RA synovial lining correlated with joint destruction (r = 0.77, P < 0.001). CONCLUSION: CD16+ monocytes, a cellular source of HC gp-39 in vivo, are overrepresented in both RA peripheral blood and synovial tissue. The presence of HC gp-39+ cells in RA synovium is correlated with the degree of joint destruction. These data support a role of these cells in the local autoimmune response that leads to chronic inflammation and joint destruction.

Adipokines↗

Raised human cartilage glycoprotein-39 plasma levels in patients with rheumatoid arthritis and other inflammatory conditions.

OBJECTIVE: To evaluate plasma human cartilage glycoprotein (HC gp-39) as a possible marker for the presence and/or activity of rheumatoid arthritis (RA) and other inflammatory conditions. BACKGROUND: HC gp-39 is a secretory product of chondrocytes, synovial cells, macrophages, and neutrophils. HC gp-39, also described as YKL-40, was found to be a marker of joint disease and tissue injury in RA and various other diseases. METHODS: Levels of HC gp-39 were determined by a sandwich enzyme linked immunosorbent assay (ELISA) in 47 patients with RA, 47 with osteoarthritis (OA), 24 with systemic lupus erythematosus (SLE), 24 with inflammatory bowel disease (IBD), and in 47 healthy controls. A disease activity score was assessed in the patients with RA, SLE, and IBD. RESULTS: The plasma level of HC gp-39 in the RA patient group was significantly higher than in the other patient groups and healthy controls. The level in patients with OA, SLE, and IBD was also significantly higher than the HC gp-39 level found in the healthy control group. HC gp-39 levels in patients with RA correlated positively with the ESR and IgM rheumatoid factor level but not with other variables of disease activity. In the patients with SLE and IBD no correlation was found with the disease activity score. CONCLUSION: The plasma level of HC gp-39 is increased in inflammatory conditions with and without joint disease (SLE, IBD, OA, and RA). Thus increased levels of HC gp-39 do not only reflect joint disease but also reflect inflammation or tissue degradation in various conditions. Notably, the highest level of HC gp-39 was found in patients with RA. Only in the RA patient group was a correlation between HC gp-39 plasma levels and some laboratory variables of disease activity found.

Adipokines↗

Genetic fusion of an alpha-subunit gene to the follicle-stimulating hormone and chorionic gonadotropin-beta subunit genes: production of a bifunctional protein.

The human glycoprotein hormones, hCG, TSH, LH, and FSH, are composed of a common alpha-subunit assembled to a hormone-specific beta-subunit. The subunits combine noncovalently early in the secretory pathway and exist as heterodimers but not as multimers. LH/FSH are synthesized in the pituitary gonadotrophs, and several of the alpha-subunit sequences required for association with either the LHbeta or FSHbeta subunits are different. Thus, it is intriguing that no ternary complexes are observed for LH and FSH in vivo (e.g. two different beta-assembled to a single alpha-subunit). To examine whether the alpha-subunit can interact with more than one beta-subunit, and to study the conformational relationships between the ligand and the receptor, we constructed a vector encoding two tandemly arranged beta-subunits fused to a single alpha-subunit gene (FSHbeta-CGbeta-alpha). This approach permitted structure-function analyses of alpha/beta domain complexes without the possibility of subunit dissociation. We reported previously that the CGbeta or FSHbeta subunit gene can be genetically fused to the alpha-gene and the resulting single chains (CGbetaalpha and FSHbetaalpha, respectively) were biologically active. Here we demonstrate that a triple-domain single chain bearing the configuration FSHbeta-CGbeta-alpha is efficiently secreted from transfected Chinese hamster ovary (CHO) cells and exhibits high-affinity receptor binding to both FSH and LH/hCG receptors, comparable to the native heterodimers. These results indicate that the alpha-subunit can interact with each beta-subunit in the same complex and that an alpha-domain fused to a beta-domain can still interact with an additional beta-subunit. The data also demonstrate the remarkable flexibility of the receptor to accommodate the increased bulkiness of the triple-domain ligand. In addition, the formation of intrachain FSH- and CG-like complexes observed in a triple-domain single chain suggests that the alpha-subunit can resonate, i.e. shuttle between alpha-beta heterodimeric intermediates during the early stages of synthesis and accumulation in the endoplasmic reticulum. Such model compounds could be useful as substrates to generate a new class of analogs in which the ratio of the LH/FSH activity is varied. This could aid in the design of analogs that could be used to mimic the in vivo hormonal profiles.

Animals↗

Structure of an Fab fragment against a C-terminal peptide of hCG at 2.0 A resolution.

3A2 is an antibody raised against human chorionic gonadotropin and recognizes a linear epitope on the C-terminal peptide of the human chorionic gonadotropin beta-subunit. Its three-dimensional structure has been determined to 2-A resolution using molecular replacement and refined to a conventional R-factor of 18.2%. The protein exhibits the typical immunoglobulin fold, and the model contains 944 ordered water molecules and one sulfate ion. A comparison of the complementarity-determining regions of the Fab3A2 with those from the Protein Data Bank following the canonical structure method reveals a canonical main chain conformation. This antibody belongs to the canonical structure class (combination of canonical conformations of the complementarity determining loops) that shows a preference for haptens and not for peptides. However, the shape of the surface of the antigen binding loops resembles that of an anti-peptide antibody.

Amino Acid Sequence↗

Crystallization of two hCG-specific monoclonal antibody fragments.

The Fab fragments of two monoclonal antibodies (Fab3A2, Fab6A) raised against epitopes of human chorionic gonadotrophin (hCG) have been crystallized using the vapour-diffusion technique. The Fab3A2 antibody recognises an epitope on the C-terminal peptide of the beta-subunit and the Fab6A a conformational epitope of hCG. Both Fab crystals grow as hexagonal rods from ammonium sulfate solutions. The Fab3A2 crystals belong to space group P3121 with a = b = 74.84, c = 198.2 A and diffract to 1.33 A at the ESRF. The Fab6A crystals are in the space group P3221 with a = b = 129.53, c = 74.40 A and diffract to 2.7 A at the Daresbury SRS. One Fab molecule per asymmetric unit is present in both crystals.

Animals↗

Aortic allograft implantation techniques: pathomorphology and regurgitant jet patterns by Doppler echocardiographic studies.

BACKGROUND: The diagnosis of allograft-specific pathology by echocardiography has important consequences for patient counseling and research. This study describes the pathomorphologic findings and color Doppler jet patterns in a consecutive series of patients after allograft placement with either the subcoronary implantation or root replacement technique. METHODS: From 1987 to July 1996, the subcoronary allograft implantation technique and root replacement technique were used in 82 patients and 70 patients, respectively. These patients comprised the study group. RESULTS: The incidence of paravalvular leaks and eccentric regurgitant jets was higher with subcoronary implantation (41%) than with root replacement (11%). Patients with a subcoronary implanted allograft had a higher incidence of eccentric jets. CONCLUSIONS: These findings support the concept of preservation of valve geometry after root replacement, as allograft-specific pathomorphologic abnormalities and eccentric jets are more common after subcoronary implantation of allografts. Learning effects, however, cannot be excluded as the cause of these abnormalities.

Adolescent↗

A comparison of adult pulmonary autograft diameter measurements with echocardiography and magnetic resonance imaging.

UNLABELLED: In 38 consecutive patients the pulmonary autograft was used in aortic root replacement. Investigations were performed with transthoracic echocardiography, transoesophageal echocardiography and magnetic resonance imaging in 31, 27 and 27 patients respectively. The mean age at operation was 28.7 years (range 19.0-52.0) and the follow-up period was 2.8 years (range 0.8-6.7). The pulmonary autograft diameter was measured at the subannular region (1), at the annulus at the hinge points of the valve leaflets (2), at the sinus (3), at the sino-tubular junction (4) and at the distal part of the autograft (5). With transoesophageal echocardiography the mean systolic measurements at levels 1 to 5 were 32, 31, 42, 35 and 34 mm, respectively. The corresponding diastolic measurements were smaller: 25, 28, 42, 35 and 34 mm respectively. There was no significant difference between transthoracic echocardiography and transoesophageal echocardiography measurements of the proximal autograft (levels 1-3). Diameters obtained with magnetic resonance imaging were 1 to 3 mm larger than those obtained with transthoracic echocardiography and transoesophageal echocardiography (P < 0.05), except the annulus at systole (P > 0.3). CONCLUSIONS: The mean pulmonary autograft diameters measured using transthoracic echocardiography, transoesophageal echocardiography and magnetic resonance imaging were larger than native aortic and pulmonary diameters of a normal population in the same age group. Diameters of the distal 2 levels could not be imaged reliably with transthoracic echocardiography. Magnetic resonance imaging diameter measurements were, in general, larger than with echocardiography.

Adult↗

Child mortality patterns in rural areas of Anhui and Henan provinces in China, 1990.

County-based IMR and U5MR in Anhui and Henan provinces in China were estimated and analyzed by using the 1990 Census Data. Census was conducted on July 1, 1990, the number of deaths only occurred in the first half year of 1990 was collected. In order to obtain the total population and total number of deaths in the same year, the total number of deaths in each age-sex group for the whole 1990 was then estimated by taking the death number in the first half of 1990 as the base and multiplying a coefficient, which varied in different age-sex-region groups. Two major adjustments for some possible under-reporting cases in female birth and infant death were made. If the sex ratio at age 0 in some counties was beyond 1.2, then it was taken as 1.15 for rural counties and 1.10 for urban cities, which were the estimates of sex ratios for the children at age 5 in the national 1% Population Sampling Survey in 1995. The adjustment for IMR were made by comparing the segment of the county lift table from age 15 through 59 with that from the same age groups in the international and Chinese Model Life Tables. The IMR in the county life table would be substituted by the one in the closest Model Life Talbe, if it was less than in the latter. The findings of the analysis may be summarized as follows: (i) Total county-based IMR and U5MR were 33.4 per 1,000 and 41.4 per 1,000 respectively, with great variations between urban cities (25.4 per 1,000 for IMR and 31.4 per 1,000 for U5MR) and rural counties (35.1 per 1,000 for IMR and 43.6 per 1,000 for U5MR). There were also significant differences in child mortality between nationally identified poor counties and other counties in rural areas. In the poor counties the total IMR was 40.7 per 1,000 living births in average while in non-poor counties it was only 33.2 per 1,000 in average (P < 0.05). The U5MR in poor counties was 25 percent higher than in non-poor counties (51.5 vs 40.9 per 1,000 living births). (ii) Statistically significant correlation between child mortality and socio-economic variables was revealed from the data set, among which gross social economic products per capita was found to have the strongest relationship with child mortality. The negative correlation was found between child mortality and a set of so-called 'rich' variables including the gross social products, gross agricultural products, gross industrial products and the proportions of high-educated population at county level, whereas the positive correlation was found between child mortality and a set of 'poor' variables, such as proportions of residents with lower level of education and illiteracy rate. (iii) Differences in child mortality between these two provinces were found, which were identical to the trends of differences in socio-economic indicators between them. Lower child mortality proved to be associated with better socio-economic conditions (higher per capita products, higher proportions of residents with higher level of education, lower proportion of less educated people and illiteracy) in province Henan. (iv) A simple linear regression model was developed separately for Henan and Anhui to predict the IMR and U5MRs in each stage of economic development, where the dependent variables were the logarithm of IMR and U5MR, and the independent variables were the quintiles of the output value of gross products (GOP). It was found that at the first quintile, which was equivalent to 800 yuan of GOP in average, the predicted IMR and U5MR would reach 40 per 1,000 and 51 per 1,000 respectively. It would decline to 38 per 1,000 for IMR and 47 per 1,000 for U5MR in the second lowest quintile. Dramatic drop of child mortality was found between the second quintile and the third quintile, where 6 per 1,000 decline would occur for both IMR and U5MR. The decline would continue subsequently, but slower. The prediction of child mortality in rural counties could be used as a reference to assess counties at different stages of socio-

Adolescent↗

Human cartilage glycoprotein-39 as a candidate autoantigen in rheumatoid arthritis.

OBJECTIVE: To identify a cartilage-derived autoantigen that is relevant to the rheumatoid arthritis (RA) disease process. METHODS: A DR4 (DRB1*0401) peptide binding motif was used for the selection of potential self reactive peptides within human cartilage glycoprotein-39 (HC gp-39), a protein that is differentially expressed at the site of chronic inflammation. Synthetic peptides accommodating the motif were tested for binding the RA-associated DR4 (DRB1*0401) molecules. High-affinity binders were then tested for their capacity to stimulate peripheral blood mononuclear cell responses in RA patients or healthy donors. To assess the arthritogenic nature of native HC gp-39, the protein was injected into BALB/c mice. RESULTS: HC gp-39-derived motif-based peptides were selectively recognized by peripheral blood T cells from RA patients. Injection of the intact protein into BALB/c mice resulted in immunity to HC gp-39, which was found to be associated with the development of a chronic, relapsing arthritis. Moreover, inhalation of the protein led to tolerization of antigen-specific T cells and to suppression of HC gp-39-induced arthritis. CONCLUSION: These data indicate that HC gp-39 is a target of the immune response in RA. Consequently, HC gp-39 is a candidate for antigen-specific immunotherapy.

Adipokines↗

Selection of self-reactive peptides within human aggrecan by use of a HLA-DRB1*0401 peptide binding motif.

The pathogenesis of joint destruction in rheumatoid arthritis remains ill-defined. Joint destruction is thought to be the result of tissue damage mediated by T cells. The mere presence of articular cartilage appears responsible for sustaining chronic synovitis and thereby forwards a role for cartilage-responsive T cells in RA. Taking advantage of the positive DRB1*0401 association with RA susceptibility, we reasoned that T-cell recognition of autoantigens in RA would be restricted by DRB1*0401-encoded molecules. A DR4 (B1*0401) peptide binding motif was used for the identification of putative T-cell epitopes within human aggrecan, a candidate autoantigen. Thirteen peptides were synthesized and tested for binding DRB1*0401 or 0404-encoded molecules. Selected binders were tested for induction of proliferative responses in peripheral blood mononuclear cells from donors carrying the DR4 or DR1 specificity. Both healthy and RA donors responded to human aggrecan-derived peptides, thereby identifying these sequences as T-cell epitopes. Interestingly, responses to aggrecan-derived epitopes were significantly decreased in RA patients compared to controls. This was not due to an overall hyporesponsiveness of RA patients since responses to a recall antigen or mitogen did not differ from controls. The data suggest that in RA, aggrecan-specific T cells may exist in a different stage of activation or may have left the periphery to home to the joint.

Adult↗

Clinical outcome and left ventricular function after pulmonary autograft implantation in children.

BACKGROUND: Aortic root replacement with a pulmonary autograft is an alternative treatment for children with aortic valve or root disease, or both. METHODS: Twenty-six patients (18 boys and 8 girls) with a mean age of 10.9 years (range, 0.3 to 16.9 years) underwent this procedures in a 7-year period. The mean follow-up period was 3.2 years (range, 0.2 to 7.5 years). RESULTS: During follow-up 3 patients died and one autograft was replaced with a mechanical valve. The actuarial survival and actuarial event-free survival rates were 87% and 79%, respectively, at both 5 and 7 years. None of the surviving patients had complaints, and all have done well and are living normal lives. Electrocardiographic signs of myocardial ischemia and left ventricular hypertrophy were not present. Echocardiography showed autograft valve regurgitation to be absent or trivial (n = 17) or mild (n = 5). Stenosis was not present. Increasing autograft annulus diameters were noted during follow-up, but this was not related to the severity of autograft regurgitation. Left ventricular dimensions and function were within normal limits later than 1 year after the operation. Only 2 patients had a moderate pulmonary stenosis without right ventricular hypertrophy. CONCLUSIONS: The surgical results, clinical outcome, valve function, and left ventricular function in our patients have been good. This procedure is recommended as a method of aortic valve replacement in children.

Actuarial Analysis↗

Does the pulmonary autograft in the aortic position in adults increase in diameter? An echocardiographic study.

OBJECTIVE: The objective of this study was to discern the fate of the pulmonary autograft diameter over time in adults and its relation to aortic regurgitation in the setting of aortic root replacement. METHODS: From January 1989 to May 1995, 36 consecutive adult patients underwent aortic root replacement with a pulmonary autograft for aortic valve disease. The mean age of 20 male and 16 female patients was 29.1 years (range 19.3 to 52.1 years). The mean follow-up was 2.3 years (range 0.3 to 6.0 years). Two patients died in the hospital. One other patient had a second operation for stenosis at the distal suture line of the allograft in the pulmonary position. Pulmonary autograft anulus and sinus diameters were measured with epicardial echocardiography before (only anulus) and after cardiopulmonary bypass, with transthoracic echocardiography at hospital discharge, and with transesophageal echocardiography during follow-up. RESULTS: The mean autograft anulus diameter did not increase immediately after cardiopulmonary bypass (mean diameter 26.2 mm before and 26.4 mm after cardiopulmonary bypass). The mean autograft sinus diameter after cardiopulmonary bypass was 36.5 mm. The mean autograft anulus diameter increased to 31.5 mm at follow-up, an increase of 5.1 mm (19%). The mean autograft sinus diameter increased to 43.9 mm at follow-up, an increase of 7.4 mm (20%). Fifty-nine percent of the anulus diameter increase and 40% of the sinus diameter increase was already reached at hospital discharge (7 to 10 days after the operation); the other part of the increase occurred during follow-up. Diameter increase was associated with neither the length of follow-up (follow-up less than 1 year compared with a longer follow-up) or severity of aortic regurgitation. CONCLUSION: Pulmonary autograft anulus and sinus diameters increase the first year after aortic root replacement with a pulmonary autograft. This occurs rapidly within 10 days after the operation, with a further increase during follow-up, without causing significant aortic regurgitation at medium-term follow-up.

Adult↗

Effects of cryopreservation on contractile properties of porcine isolated aortic valve leaflets and aortic wall.

Human semilunar donor heart valves can be stored in banks, awaiting transplantation. To evaluate the result of the preservation protocols, a quantitative description of the tissue is necessary. In this study we investigated in a quantitative way the contractile properties of fresh and cryopreserved porcine isolated aortic heart valve leaflets in response to a number of endogenous vasoactive compounds. The responses of strips of the aortic wall were included for comparison. Contraction was measured isometrically in response to potassium (K+; 100 mmol/L), 5-hydroxytryptamine (1 nmol/L to 100 micromol/L), noradrenaline (1 nmol/L to 100 micromol/L), endothelin-1 (0.01 nmol/L to 0.3 micromol/L), and prostaglandin F(2alpha) (0.1 nmol/L to 10 micromol/L). The pharmacologic parameters E(MAX) (the maximal response expressed as a percentage of contraction to a 100 mmol/L dose of K+) and EC50 (the concentration that produces 50% of the maximal effect) were calculated for every compound (n = 6 to 7 each). We observed that all specimens contracted in response to potassium. Its magnitude in fresh leaflets equaled 1.6 +/- 0.14 mN compared with 26.6 +/- 2.6 mN in fresh aortic wall. Noradrenaline, endothelin-1, and prostaglandin F(2alpha) all caused contraction in valvular leaflets and aortic wall, whereas 5-hydroxytryptamine caused contraction in the valvular leaflets but relaxation in aortic wall. After cryopreservation, the response to K+ amounted to 24% of the response of the fresh specimens in valvular leaflets (n = 25) and 14% in aortic wall (n = 26). The values of E(MAX) and EC50 of the responses to noradrenaline, endothelin-1, and prostaglandin F(2alpha) remained unchanged. Although the physiologic relevance of contraction of valvular leaflets needs further study, its measurement may provide an additional model to verify the consequences of alternative methods of preservation.

Animals↗