Human Heart Valves Research Articles

Quantitative analysis of human heart valves: Does anorexigen exposure produce a distinctive morphological lesion?

The need for more detail regarding the clinical and morphological features of human heart valves has become evident due to recent controversy regarding anorexigen-associated valvular dysfunction. In the present study, we used quantitative digital image analysis of geometric and compositional features to compare the histopathology of cardiac valves excised from patients treated with anorexigens as compared to normal, floppy, rheumatic and carcinoid valves. Anorexigen-exposed valves had the greatest number of onlays/valve ( P<.0001), while rheumatic valves showed the greatest average onlay size and thickness of the comparison groups studied ( P=.01). The valve onlays from anorexigen-exposed, carcinoid and floppy valves contained a greater percentage of glycosaminoglycans (GAGs) as compared to normal and rheumatic valves ( P=.01). The anorexigen-exposed valve propers contained more GAGs than any other comparison group ( P=.02). Vessels were prominent in both onlay and valve proper regions of carcinoid valves, in the anorexigen-exposed valve onlays and in rheumatic valve propers. Thus, the number of onlays, their size, the degree of GAG deposition, and the presence and location of vessels and leukocytes were important features distinguishing anorexigen-exposed valves from normal valves. Discriminant analyses, based on geometry, color composition or color composition, and vessel and leukocyte counts combined, were able to separate the valves into distinguishable groups. Our findings demonstrate that specific microscopic features can be used to separate anorexigen-associated heart valve lesions from normal valves and valve lesions associated with other pathologies, and suggest that a distinctive pathological process may exist in many anorexigen-exposed valves.

The challenge of defining normality for human mitral and aortic valves: Geometrical and compositional analysis

Advances in digital imaging technology and in tools for obtaining detailed quantitation of morphological features have facilitated a new approach to pathological assessment of many tissues, including heart valves. In the present study, we quantitatively examined the tissue geometry and composition of structurally normal mitral and aortic valves removed at autopsy or surgery from patients aged 15–84 years. Through univariate analyses of quantitative variables, we have determined which features change distinctively with age. The anterior mitral valve leaflet (AMV) underwent a statistically significant decrease in area of the valve proper and an increase in the number of superficial tissue accumulations called onlays as the patients aged. For all geometric variables measured in the aortic valve, increases were seen with age, leading to a thicker valve, with enlargement of the valve proper and onlays, and with changes in the number of onlays. The mitral valve proper, composed largely of collagen in younger individuals, showed significant increases in glycosaminoglycans and elastin and a relative decrease in collagen with age. The compositional characteristics of the aortic valve proper were similar to those of the mitral valve, with a dramatic relative increase in elastin and a decrease in collagen with age. Valve onlays, when present, were similar in composition to the valve proper for both valves. Our findings regarding normal valve tissue composition, when taken in the context of geometrical features, and together with evidence of age-related changes in the relative amounts of specific constituents, provide a basis on which to analyze human heart valves affected by various known or putative diseases.

Unsteady flow through a new mechanicalheart valve prosthesis analysed by digital particle imagevelocimetry

Digital particle image velocimetry was used to study thepulsatile flow through a new mechanical heart valve prosthesis. Thedesign of the new prosthesis with three leaflets in symmetricarrangement is similar to the human aortic heart valve. A fullytransparent 1:1 model of the valve was used for laser-based flowvisualization and velocity measurements to optimize the valve design.Planar velocity field measurements of the time-dependent flow fieldand high-speed recordings of the occluder motion were carried out inphysiological pulsatile flow. The new valve shows a well-defined coreflow with small wakes behind the leaflets. The specific three-leafletdesign yields a desired wash-out effect of the stagnant regions inthe aortic sinuses during valve opening and closure. The leafletsbegin to close in an early stage of the end of the flow cycle whichis promoted by induced backflow near the walls and the sinuses. Thisleads to a relatively smooth valve closure and a reduced impactvelocity.

Advances towards understanding heart valve response to injury

Background: Composed of endocardial endothelial, valvular interstitial, cardiac muscle, and smooth muscle cells (SMC), heart valves are prone to various pathologic conditions the morphology of which has been well described. The morphology of diseased valves suggest that the “response to injury” process occurs in these valves, and is associated with an accumulation of interstitial cells and matrix, valvular inflammation and calcification, conditions that lead to dysfunction. The purpose of this study is to describe the current knowledge of the regulation of the valvular “response to injury” process, since we feel that this paradigm is essential to understanding valve disease. Methods: The pertinent literature relating to the cell and molecular biology of valvular repair, and specifically interstitial cell function in valve repair, is reviewed. Results: The cell and molecular biology of valve interstitial cells are poorly understood. Molecules regulating some of the aspects of the “response to injury” process have been studied, however, the signal transduction pathways, gene activation, and interactions of bioactive molecules with each other, with cells, and with the matrix have not been characterized. Initial studies identify the cell and molecular biology of interstitial cells to be an important area of research. Agents that have been studied include nitric oxide (NO) and FGF-2 and several matrix-related proteins including osteopontin. The present review suggests several directions for future study and a working model of valvular repair is presented. Discussion: The regulation of the “response to injury” process in the human heart valve is still largely unknown. The cell and molecular events and processes that occur in heart valve function and repair remain poorly understood. These events and processes are vital to our understanding of the pathobiology of heart valve disease, and to the successful design of tissue engineered replacement valves.

Physicochemical and microscopical study of calcific deposits from natural and bioprosthetic heart valves. Comparison and implications for mineralization mechanism.

Natural and bioprosthetic heart valves suffer from calcification, despite their differences in etiology and tissue material. The mechanism of developing calcific deposits in valve tissue is still not elucidated. The calcific deposits developed on human natural and bioprosthetic heart valves have been investigated and compared by physicochemical studies and microscopy investigations and the results were correlated with possible mechanisms of mineral crystal growth. Deposits from 16 surgically excised calcified valves (seven natural aortic and nine bioprosthetic porcine aortic valves) were examined by chemical analysis, FTIR, XRD, and SEM-EDS. The Ca/P molar ratio of the deposits from bioprosthetic valves (1.52+/-0.06) was significantly lower compared to that of the natural valves (1.83+/-0.03) (p=0.05, 1-way ANOVA). SEM-EDS examination of the two types of valve deposits revealed the coexistence of large (>20 microm) and medium (5-20 microm) plate-like crystals as well as microcrystalline (<5 microm) calcium phosphate mineral formations. The results confirmed the hypothesis that the mineral salt of calcified valves is a mixture of calcium phosphate phases such as dicalcium phosphate dihydrate (DCPD), octacalcium phosphate (OCP) and hydroxyapatite (HAP). DCPD and OCP are suggested to be precursor phases transformed to HAP by hydrolysis. The lower value of the Ca/P molar ratio found in the bioprostheses, in comparison with that corresponding in natural valves, was ascribed to the higher content in these deposits in precursor phases DCPD and OCP which were subsequently transformed into HAP. On the basis of chemical composition of the deposits and their morphology it is suggested that crystal growth proceeds in both types of valves by the same mechanism (hydrolysis of precursor phases to HAP) in spite of their differences in etiology, material, and possible initiation pathways.

Cardiovascular Mechanics: Investigation of Two Components, Tissue Heart Valves and Blood Cells

A fundamental anatomical composition of the heart valves is presented along with its relationship to the tissue mechanical behavior. During the loading and unloading phases of the tissue different stress strain pathways are followed with the curves composing the characteristic hysteresis loop, exhibiting the viscoelastic mechanical behavior of valvular tissue. The storage modulus and the phase shift (tan δ) as well as the ‘collagen’ modulus of human heart valves were measured in orthotropic directions using uniaxial dynamic tensile tests at 10 Hz. Viscoelastic properties of human erythrocytes are presented as calculated from micropipette aspiration experiments. Employing the hemorheometre, from filtration experiments an index of rigidity (IR) of erythrocytes is estimated. A relationship between the global parameter IR and the shear elastic modulus of erythrocyte membrane, μ, is established. The same two techniques adapted for leukocytes and their subpopulations have been used and a relationship between the rigidity index of leukocytes (ILR) and their apparent bulk viscosity (ηapp), has been found.

Increased numbers of circulating donor-specific T helper lymphocytes after human heart valve transplantation.

Implantation of cryopreserved human donor heart valves for either congenital or acquired cardiac disease has been performed since the last three decades. Although the clinical outcome is good, long-term valve degeneration resulting in dysfunction has been observed. A specific immunological response of the recipient against the allograft has been proposed as one of the factors involved in this process. Helper T lymphocytes play an important intermediate role in cellular and humoral immune response. Increasing numbers of circulating donor-specific helper T lymphocytes precursors (HTLp) correlate with graft rejection after organ transplantation. To investigate whether cryopreserved human donor heart valves are able to induce a donor-specific T helper response, we monitored the HTLp frequencies (HTLpf) in peripheral blood samples of 13 patients after valve allograft transplantation by use of a limiting dilution assay followed by an interleukin-2 bioassay. Prior to transplantation, HTLpf specific for donor and third-party antigens showed individual baseline levels. After allografting, the antidonor frequencies significantly increased in 11 of the 13 patients (P = 0.02). This was not found for stimulation with third-party spleen cells (P = 0.68), which indicates a donor-specific response. Maximal donor-specific HTLpf were already found at 1--2 months after operation. Valve allograft transplantation induces an increase in the numbers of donor-specific HTLp in peripheral blood of the patients. Analogous to organ transplantation, these HTLp may play a crucial role in events that lead to valve damage. Therefore, monitoring of HTLp in peripheral blood samples might be informative for donor valve degeneration (rejection) and subsequently valve allograft failure.

Changes in the collagen structures of human heart valves in relation to age and hypertension

Using polarization microscopy and morphometrical methods, the influence of hypertension on the collagenous structures in the Lamina fibrosa of bicuspid valves of 14 middle-aged persons (30 to 50 years) were examined. The measurements were performed on histological sections. A group of 14 middle-aged subjects free from heart disease served as the control group. Furthermore, the results were compared to earlier findings on the histological biomorphosis of the atrioventricular valves. The following changes were observed and quantitatively determined: a) an enhancement of the percentage of the mechanically more resistant collagenous fibers (unsilvered, type I collagen), b) a stronger lateral aggregation of the collagenous fibrils of both types I and III collagen, c) a significant decrease of the total numbers of collagenous fibers per measuring area, and d) a significant decrease of the portion of silvered fibers (type III collagen) per measuring area for both sexes. The fiber density distributions confirm the observed changes: in the hypertension group the collagenous fibers are less densely distributed than in the control group. The observed regression of the content of collagenous fibers in the hypertension group is probably due to the anti-hypertensive treatment. Following the findings the turn-over of type III collagen is stronger influenced than that of type I collagen. The initial results determined in human heart valves confirm findings in animal models and characterize them with regard to the collagen types mentioned.

The isoprostane 8-epi-PGF 2α is a valuable indicator of oxidative injury in human heart valves

To date, little information is available concerning oxidative injury in human cardiac valves. Therefore, we sought to investigate whether the isoprostane, 8-epi-PGF 2α, a novel oxidative stress marker, is localized in aortic and pulmonary valves derived from explanted hearts of patients suffering from idiopathic dilative cardiomyopathy (IDC). By using semiquantitative immunohistochemistry, we demonstrated that 8-epi-PGF 2α is localized in both valves with pulmonary valves accumulating more of this isoprostane compared to aortic valves (36.69±12.04% vs. 31.54±11.49%, P<.05). These results were confirmed by a radioimmunoassay (RIA) analysis showing a similar, but not significant, difference between the two valves (288.50±72.18 pg/mg protein in the pulmonary valves and 267.30±58.77 pg/mg protein in aortic valves, P=.09). Considering the data presented in this study, we suggest that 8-epi-PGF 2α is a valuable indicator of oxidative injury in human semilunar valves.

The crystallization of calcium carbonate on porcine and human cardiac valves and the antimineralization effect of sodium alginate

The use of biprosthetic valves remains limited, due to poor long-term durability, primarily as a result of tissue calcification. Porcine and human cardiac valve leaflets were found to be a substrate favoring the deposition of vaterite crystals from stable supersaturated solution at pH 8.5 at 25°C. The apparent order for vaterite crystallization reaction was found to be n=1, suggesting a surface diffusion controlled mechanism. The crystallization was studied by the constant composition technique, thus making it possible for relatively large amounts of the overgrowth phase to be formed and identified exclusively as vaterite. Analysis of the initial rates of the reaction as a function of the solution supersaturation, according to the classical nucleation theory, yielded a value of 23.4 mJ m −2 for the surface energy of the growing phase and a three-ion cluster forming the critical nucleus. A novel “in vitro” anticalcification process based on the treatment of porcine and human heart valves with sodium alginate has been developed. This anticalcification procedure reduced mineralization of porcine and human valves up to 53% and 45%, respectively. Kinetic analysis according to a Langmuir type adsorption isotherm lead to the calculation of an affinity constant K aff =19.3×10 4 mol −1 dm 3 for the adsorption of sodium alginate to the substrate.

Influence of mineral components on laser-induced fluorescence spectra of calcified human heart-valve tissues

Laser-induced fluorescence (LIF) spectra of calcified human heart-valve tissue and LIF spectra of macroscopic calcinosis fragments dissected from human heart valves were compared with LIF spectra of pig myocardium tissues. Excitation was provided by an excimer laser with wavelength lambda = 248 nm. Fluorescence bands that were due to mineral and organic tissue components were identified by measurement of LIF spectra of macroscopic fragments of calcified tissues that had been heat treated at 700 degrees C. The studies showed that LIF spectra of calcified tissues include fluorescence emission from tryptophan, collagen, elastin, and a mineral component of tissue, hydroxylapatite. The observed differences in LIF spectra of normal and calcified tissues with different pathologies may result not only from calcification-induced changes in relative collagen and elastin concentrations but also from additional (absent in normal heart tissue) fluorescence of hydroxylapatite. The calcification-induced changes in the LIF spectra of human heart-valve tissues, characterized by a 330/450 nm ratio, were found to be quite appreciable, which suggests that this ratio can be used with LIF measurements to evaluate the degree of heart-tissue calcification.

The influence of aging and aortic stiffness on permanent dilation and breaking stress of the thoracic descending aorta.

To assess the influence of aging and aortic stiffness on the extent of irreversible deformation and breaking stress of the human thoracic aorta. From 14 human heart valve donors without aortic disease (mean age 35 years, range 8-59 years), 14 intact segments of the thoracic descending aorta were studied within 48 h after cardiac arrest. In an experimental setup, the segments were submitted to increasing hydrostatic pressure loads, both statically and dynamically, while radius and wall thickness were monitored echocardiographically. Pressure-radius curves were constructed. Radius and wall thickness were determined at a pressure of 100 mmHg. Radius at elastin resting length and collagen recruitment pressure (Pcol, mmHg) were derived from the pressure-radius relationship and stress-strain curves were constructed to yield Young's moduli of elastin and collagen. Distensibility (D, mmHg-1) was determined while loading the segment with a sinusoidal pressure wave of 120/50 mmHg at both 0.5 and 1 Hz. Subsequently increasing static pressure loads of 400, 800, 1200 and 1600 mmHg were applied. After each pressure load, the increase in aortic radius at a pressure of 100 mmHg (Rinc) was determined. The experiment continued until rupture occurred and breaking stress (sigma break, N m-2) was calculated, donor age and aortic stiffness were correlated with Rinc and sigma break of the aortic segments. Mean breaking stress of the 14 segments was 2.7 x 10(6) N m-2. Breaking stress was negatively correlated with age (r2 = 0.66) and positively with D (r2 = 0.44) and with Pcol (r2 = 0.18). Seven segments survived a pressure load of 800 mmHg, in these vessels, the extent of irreversible dilation was positively correlated with age (r2 = 0.42) and negatively with D (r2 = 0.40) and Pcol (r2 = 0.40). Permanent deformation and rupture of the human thoracic aorta following pressure overload are influenced by age, distensibility and collagen recruitment pressure.

Effect of antibiotic pretreatment on immunogenicity of human heart valves and component cells

Background. For many years valves have been sterilized with high-dose antibiotics before implantation, but now there is an increasing trend to using “homovital” valves, which have been exposed to very low dose antibiotics. Methods. To investigate the immunogenicity of valve tissue, before and after exposure to high- and low-dose antibiotics, peripheral blood mononuclear cells and human allogenic T cells were cocultured with antibiotic-treated valve discs, cultured valve endothelial cells, and fibroblasts. Proliferation was measured by uptake of thymidine labeled with hydrogen 3. Results. Untreated tissue pieces stimulate peripheral blood mononuclear cells (4,080 ± 980 cpm) at day 0 with similar results after 1 day in Hank’s balanced salt solution (4,272.4 ± 1,307 cpm) reducing to 2,442 ± 926 cpm after 3 days and 1,111 ± 255 cpm after 5 days; antibiotic-treated pieces are less immunogenic after 1 (2,560 ± 403 cpm), 3 (1,550 ± 60 cpm), 5 (717 ± 295 cpm), and 7 days (633 ± 174 cpm) in homovital solution, whereas sterilized pieces are not immunogenic (184 ± 96 cpm) after only 1 day in strong antibiotics. Histologic analysis showed that this corresponds to a reduction of class I and class II expression by human valve endothelial cells. Human valve endothelial cells but not fibroblasts are capable of causing direct stimulation of CD4+ T cells. However, human valve endothelial cells poorly stimulate CD4+ T cells after incubation in homovital solution for 24 hours. Conclusions. This study shows that valve tissue is immunogenic and this immunogenicity is mediated mainly by endothelial cells. However, the immunostimulatory potential of the valve can be reduced by incubating the solution in an antibiotic cocktail.

Quantification of Mitral Regurgitation by the Automated Cardiac Output Method: An In Vitro and In Vivo Study

Background: Recently, the automated cardiac output method (ACM) was introduced for the calculation of blood flow at the left ventricular outflow tract (LVOT). This study was performed to examine the possibility of using ACM for flow calculation at the level of the mitral valve and for the quantification of mitral regurgitation (MR) in vitro and in vivo. Methods and Results: In a computer-controlled in vitro model of the human heart, aortic and mitral normal bioprosthetic valves were inserted. ACM and electromagnetic probe flow measurements correlated well at the LVOT and at the mitral level ( r 2 = 0.79 and 0.77, respectively). For stroke volumes ranging from 30 to 100 ml/beat, there was no statistically significant bias between ACM and electromagnetic flow probe (-1.5 and 1.3 ml for LVOT and mitral level, respectively). Limits of agreement were [-14; +11] ml and [-18; +16] ml, respectively. We evaluated 68 patients in our in vivo study. They were divided into three groups according to the results of “standard” echocardiographic Doppler methods for the semiquantification of MR: echocardiographic color Doppler cartography, intensity of the continuous wave Doppler spectra, and in some patients, pulmonary venous flow, conventional Doppler, and proximal isovelocity surface area quantitative data. Group 1 consisted of 35 patients without MR or a physiologic one; the 17 patients in group 2 had a mild MR (1-2/4) and in group 3, 16 patients with MR 3-4/4 were included. Regurgitant volume (RV) was calculated as the difference between ACM mitral flow and ACM aortic flow, and regurgitant fraction (RF) was defined as the ratio between RV and ACM mitral flow. When mitral flow was measured only from the four-chamber view, we found in group 1, RV = -0.57 (0.67) L/min and RF = -16% (19%); in group 2, RV = -0.31 (1.06) L/min and RF = -8% (19%); and in group 3, RV = 1.53 (0.94) L/min and RF = 23% (13%). RV and RF were statistically higher in group 3 compared with group 2 or group 1 ( p < 0.0005), but no significant difference was found between groups 1 and 2. When mitral flow was measured by the mean value of ACM four-chamber and two-chamber views, this resulted in group 1, RV = –0.26 (0.63) L/min and RF = –8% (15%); in group 2, RV = 0.01 (1.04) L/min and RF = -2% (18%); and in group 3, RV = 2.07 (1.21) L/min and RF = 34% (19%). RV and RF were again significantly higher in group 3 ( p < 0.0001). There was no significant difference between group 1 and group 2, but in group 1 RF was no longer statistically different from 0%. Conclusions: (1) In our in vitro setting, ACM is reliable both at the LVOT and at the mitral valve. (2) In the in vivo situation, some overlapping does exist between the three groups of MR. However, ACM is a very easy, rapid, and objective method to differentiate hemodynamic nonsignificant (<3/4) from significant (≥3/4) MR. Together with other well-known methods for the quantification of MR, it should facilitate the gradation of MR in the clinical setting. The absence of significant differences between group 1 and group 2 proves that the accuracy of ACM measurements at the mitral valve needs to be ameliorated before ACM can be used as a gold standard for the noninvasive measurement of RV and RF. (J Am Soc Echocardiogr 1998;11:643-51.)

Calcification of porcine and human cardiac valves: testing of various inhibitors for antimineralization.

Despite distinct advantages over mechanical cardiac valve prostheses, the use of bioprosthetic valves remains limited, due to poor long-term durability, primarily as a result of tissue calcification. A novel in vitro, anticalcification process based on treatment of porcine and human heart valves with metallocene dichlorides, as well as with amino acids (phenylalanine, aspartic acid, glutamic acid), has been developed. This anticalcification process reduced mineralization of porcine and human valves up to 32% and 28%, respectively.

Pathology Of Explanted Cryopreserved Allograft Heart Valves: Comparison With Aortic Valves From Orthotopic Heart Transplants

Objective: We sought to determine the morphology, mechanisms of deterioration, cellular viability, extracellular matrix integrity, and the role of immune responses in the dysfunction of cryopreserved aortic and pulmonic valve allografts. Methods: We studied 33 explanted left-sided ( n = 20) or right-sided ( n = 13) cryopreserved human allograft heart valves explanted several hours to 9 years after operation, 14 nonimplanted allografts, and 16 aortic valves removed from transplanted allograft hearts 2 days to 4 years after operation. Analysis included gross inspection, radiography, light microscopy, electron microscopy, and immunohistochemical studies. Results: Allografts implanted for more than 1 day had progressive collagen hyalinization and loss of normal structural complexity and cellularity, including endothelium and deep connective tissue cells. Inflammatory cells were generally minimal or absent in the allografts. Transmission electron microscopy of long-term cryopreserved allograft valves revealed no viable cells, focal calcification centered around dead cell remnants, and distorted but preserved collagen. In contrast, aortic valves from transplanted hearts showed remarkable structural preservation, including endothelium and abundant deep connective tissue cells; inflammatory infiltrates were generally mild and of no apparent deleterious consequence, including valves from patients who died of fatal rejection. Conclusions: Cryopreserved allografts are morphologically nonviable; their collagen is flattened but largely preserved. They are unlikely to grow, remodel, or exhibit active metabolic functions, and their usual degeneration cannot be attributed to immunologic responses. In contrast, aortic valves of transplanted hearts maintain near-normal overall architecture and cellularity and do not show apparent immunologic injury, even in the setting of fatal myocardial parenchymal rejection or graft arteriosclerosis. (J Thorac Cardiovasc Surg 1998;115:118-27)

Initial Rietveld characterisation of biological calcifications

X-ray diffraction data has been collected from biological calcific mineral associated with human bone, breast tissue, ureteric calculi, heart valve, and aorta. All the materials are shown to have a nominal calcium hydroxyapatite structure and Rietveld analysis has been performed to extract microstructural information. All refinements achieved a final Rwp value of &lt;10%. The lattice parameter ranges are a=9.375(3)(breast)−9.4316(8)(heartvalve), c=6.866(1)(uretericcalculi) −6.899(1)(rib), and crystallite size range from 40 Å (breast) to 99 Å (ureteric calculi). A correlation between crystallite size estimates from this Rietveld analysis and line profile methods is demonstrated. The results are supported by an infrared study and previous data from alternative techniques. Thus, it is demonstrated that the microstructure of these materials may be characterised by application of the Rietveld method.

Immunogenicity of human heart valve endothelial cells and fibroblasts

Immunogenicity of human heart valve endothelial cells and fibroblasts

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 μmol/L), noradrenaline (1 nmol/L to 100 μmol/L), endothelin-1 (0.01 nmol/L to 0.3 μmol/L), and prostaglandin F 2α (0.1 nmol/L to 10 μmol/L). The pharmacologic parameters E MAX (the maximal response expressed as a percentage of contraction to a 100 mmol/L dose of K +) and EC 50 (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 2α 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 EC 50 of the responses to noradrenaline, endothelin-1, and prostaglandin F 2α 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. (J Thorac Cardiovasc Surg 1997;113:165-72)

Increased expression of matrix proteins associated with calcification is common to native human and porcine xenograft biopoprosthetic heart valves

Increased expression of matrix proteins associated with calcification is common to native human and porcine xenograft biopoprosthetic heart valves