A synthetic leaflet heart valve with improved opening characteristics

A new geometry for the design of polyurethane leaflet heart valves has been investigated. The geometry termed the ‘alpharabola’ has a radius of curvature that increases from the centre of the leaflet at the free edge towards the base of the valve and perimeter of the leaflet. The hydrodynamic function and leaflet opening characteristics of the new valve design have been compared to a valve with a spherical leaflet geometry using the same material. The pressure and flow required to open alpharabola leaflets in steady flow tests was markedly lower than for spherical leaflets. Under pulsatile flow conditions with the valve leaflets fully open, the pressure drop across the alpharabola and spherical leaflets was similar, but much lower than in a porcine bioprosthesis. High speed photography showed that the alpharabola leaflets opened in less than 30 ms with the leaflet opening initiating in the base of the leaflet where the radius of curvature was larger. The synthetic leaflet valve has demonstrated short term durability in accelerated fatigue tests to 100 million cycles.     

A novel nanocomposite polymer for development of synthetic heart valve leaflets

A novel nanocomposite polymer with a polycarbonate soft segment (PCU) and polyhedral oligomeric silsesquioxanes (POSS) nanoparticle (POSS–PCU) has been selected for a synthetic heart valve due to its superior biocompatibility and in vivo biostability. However, the development of synthetic heart valves from polymeric materials requires an understanding of the basic mechanical and surface properties of the polymer. In this study, the mechanical properties of POSS–PCU, including tensile strength, tear strength and hardness, were tested and compared to control (PCU). The surface property was analyzed using contact angle measurement and the resistance to platelet adhesion was also investigated. POSS–PCU (hardness 84 ± 0.8 Shore A) demonstrated significantly higher tensile strength 53.6 ± 3.4 and 55.9 ± 3.9 N mm⁻² at 25 and 37 °C, respectively) than PCU (33.8 ± 2.1 and 28.8 ± 3.4 N mm⁻² at 25 and 37 °C, respectively). Tensile strength and elongation at break of POSS–PCU was significantly higher than PCU at both 25 and 37 °C (P < 0.001). POSS–PCU showed a relatively low Young’s modulus (25.9 ± 1.9 and 26.2 ± 2.0 N mm⁻²) which was significantly greater in comparison with control PCU (9.1 ± 0.9 and 8.4 ± 0.5 N mm⁻²) at 25 and 37 °C, respectively, with 100 μm thickness. There was no significant difference (P > 0.05) in tear strength between POSS–PCU and PCU at 25 °C. However, tear strength increased significantly (P < 0.001) (at 37 °C) as the thickness increased from 100 μm (51.0 ± 3.3 N mm⁻¹) to 200 μm (63 ± 1.5 N mm⁻¹). The surface of POSS–PCU was significantly less hydrophilic than that of PCU.     

New synthetic mitral valve model for human prolapsed mitral valve reconstructive surgery for training

Abstract

The training process of young surgeons is highly desirable in order for them to gain an understanding of the quality of care and patient safety required during cardiac surgeries, however, it may take a few years of practice in order for them to properly develop these skills. Artificial life-like platforms and models are extremely recommended for teaching hands-on and real-world practice in both junior and even experienced medical professionals and surgeons. Suitable and accessible training tools are of significant importance for simulating a particular surgery in order to provide practice opportunities for a specific surgical procedure. In this study, we focussed on the simulation of the human mitral valve prolapse reconstructive surgery. An innovative, artificial, biomimetic model was designed and fabricated made of Cryogel biomaterial developed in our lab that is suitable for the precise practice on the mitral valve prolapse model. The proposed model is mainly made up of polyvinyl alcohol (PVA) cryogel, which is designed to resemble the geometric and mechanical properties of a diseased (prolapse) mitral valve. We simulated the constructive prolapsed mitral valve surgery entirely on a synthetic platform. The platform was made available to four certified cardiac surgeon and there were unanimously very positive with no considerable differences in the procedural assessments between them. The proposed model has a similar appearance and texture to that of a diseased mitral valve and holds consistent mechanical properties to those of the real tissue. The offered technology may be used for other cardiothoracic reconstructive surgeries with high precision and consistency.     

Somnogenic activities of synthetic lipid A.

Bacterial infections and various immune response modifiers, including endotoxin and its lipid A moiety, alter sleep duration. The purpose of this study is to amplify our understanding of lipid A structure-somnogenic-pyrogenic activity relationships. Four synthetic disaccharide analogs of lipid A (LA-15-PP, LA-15-PH, LA-16-PH, and LA-18-PP) and a biosynthetic monosaccharide analog of lipid A (lipid X) were tested in rabbits for their effects on slow-wave sleep, rapid-eye-movement sleep, electroencephalographic slow-wave (0.5- to 4.0-Hz) amplitudes, and brain-colonic temperatures. Substances were injected intravenously and intracerebroventricularly. Compound LA-15-PP was the most potent; it significantly increased slow-wave sleep, delta electroencephalographic amplitudes, and brain-colonic temperatures while reducing rapid-eye-movement sleep. Compound LA-15-PH (monophosphoryl analog of LA-15-PP) induced effects similar to those of LA-15-PP, although the responses were weaker. Compound LA-18-PP induced increases in slow-wave sleep and delta amplitudes only after high doses, whereas compound LA-16-PH was devoid of these activities at the doses tested. Intracerebroventricular, but not intravenous, injections of lipid X induced small but significant increases in both slow-wave sleep and rapid-eye-movement sleep without affecting delta amplitudes or brain-colonic temperatures. These data suggest that the somnogenic actions of these lipid A analogs depend on the acylation or phosphorylation pattern and backbone structures of the molecules. Their soporific activities parallel their relative behaviors in other biological assays.     

Long-term histologic features of synthetic chordal replacement for mitral valve repair: a case report.

Expanded polytetrafluoroethylene (e-PTFE) sutures have been used with increasing frequency to replace chordae tendineae in mitral valves prolapsing because of myxoid change. A case is reported where fibrosis and calcification of the endocardial overgrowth covering the synthetic chordae led to severe mitral regurgitation 7 years after plastic repair and required mechanical prosthetic valve implantation.     

Immunogenicity and antigenicity of synthetic Escherichia coli lipid A.

The immunogenicity and antigenicity of synthetic Escherichia coli lipid A (compound 506) and its 1- and 4'-monophosphorylated derivatives (compounds 505 and 504, respectively) and nonphosphorylated derivative (compound 503) were compared with those of bis- and 4'-monophosphorylated natural free lipid A from E. coli. The synthetic compounds under study were either coated onto sheep erythrocytes (except for the water-insoluble preparation 503) or incorporated into liposomes and used for the immunization of rabbits. Both types of immunogens (the latter representing fully synthetic immunogens) resulted in high-titered polyclonal antisera which were characterized before or after absorption in a passive hemolysis assay as well as in a passive hemolysis inhibition assay with the synthetic compounds as test antigens. All antisera were found to react with their corresponding homologous antigens coated onto sheep erythrocytes, with titers of up to 2,048, and were comparable to those antisera obtained after immunization with natural lipid A exposed on the bacterial surface after acid hydrolysis. Antisera against bisphosphorylated compound 506 were highly specific for the homologous antigens, showing no interaction with compounds 504 and 505 in the passive hemolysis test. The same held true for the absorption experiments in which glutaraldehyde-fixed sheep erythrocytes were sensitized with the respective antigens. Antisera against monophosphorylated compounds 504 and 505 exhibited, besides their expected homologous reactivity, complete cross-reactivity with compound 506, but they did not cross-react with each other. Thus, anti-504 and anti-505 antibodies recognized distinct antigenic determinants, being related to the ester linked 4'-phosphate or the glycosidically linked 1-phosphate, respectively. Both antigenic determinants were also expressed by bisphosphorylated compound 506 used as an antigen; however, upon immunization, only antibodies against compound 506 were elicited.     

Experimental ischemic heart disease--effects of synthetic thromboxane A2.

Two milliliters of thromboxane A₂ (TXA₂) solution was perfused in the coronary arteries by the balloon catheter inserted through right common carotid artery in rabbits. TXA₂ was converted from prostaglandin H₂ (PGH₂) with thromboxane A₂ synthetase in platelet microsomes. Serial changes on the ECG and hypotension were observed first hour after the injection in nine out of 11 studied rabbits. Six out of the seven autopsied rabbits showed myocardial ischemia or necrosis histologically. But four control rabbits that were injected with 2 ml inactivated 1.0 μg TXA₂ solution did not show any change. The changes on the ECG were dose-dependent in 1.0, 0.5, and 0.1, μg TXA₂ solution. In addition, the ECG and the blood pressure changes by 1.0 μg TXA₂ solution were suppressed by pretreatment of a non-specific antagonist of TXA₂, phthalazinol (1 mg/kg). These findings support the concept that TXA₂ is the principal active substance in the filtrate of aggregated platelets that induced acute myocardial ischemia and necrosis in rabbits in a previous experiment.     

A synthetic tissue kallikrein inhibitor suppresses cancer cell invasiveness.

Serine proteinases modulate the interaction of tumor cells with extracellular matrix components during extravasation and metastasis. The serine proteinase tissue kallikrein has been previously demonstrated in several human adenocarcinomas, and we presently report the localization of immunoreactive kallikrein and its mRNA in pancreatic adenocarcinoma. In addition, a synthetic peptide-based inhibitor specific for tissue kallikrein (FE999024) was used in our studies to explore a possible role for kallikrein in cancer cell invasiveness. Matrigel invasion assays were performed with a human breast-cancer cell line, MDA-MB-231, which expresses tissue kallikrein in culture. In the presence of FE999024 invasion through Matrigel was inhibited in a dose-dependent manner to a maximum of 39%. We also developed a novel ex vivo assay in which breast cancer cells are infused into the pulmonary circulation of artificially ventilated explanted rat lungs. At intervals up to 6 hours after infusion pulmonary invasion was quantified by bronchial alveolar lavage to recover human cancer cells from the airspace. Invading cells in the lung interstitium were also quantified after immunohistochemistry with a monoclonal antibody specific for human cytokeratin 18. The synthetic kallikrein inhibitor attenuates breast cancer cell invasion into the airspace by 33% when quantified by lavage recovery and up to 34% as quantified in the lung interstitium by cytokeratin 18 immunostaining. Our results indicate tissue kallikrein may participate in the invasion and metastasis of human adenocarcinomas. The newly developed explanted rodent lung assay should be useful for the study of cancer cells, neutrophils, or other extravasating cells.     

A miniature gas-pressure valve

A thin, small, nonbleeding gas-pressure valve has been specially developed for prosthetic applications. With the introduction of a special membrane design, the difficulties in the miniaturisation of pressure valves could be overcome. A mathematical model of the pressure valve is presented. It shows that a fundamental relationship exists between the force acting on the membrane and the hysteresis in the input/ output characteristic; the product of these two quantities depends mainly on the inlet-valve diameter. Therefore, miniaturisation led to the construction of a pressure valve with a low operating force and reasonable hysteresis. In the prototype, a special valve-forming technique has been used. With this technique the valve nozzles are made from metal foil, permitting the construction of a thin, miniature (7×9×2·5 mm) pressure valve.     

Understanding valve/host interactions through explanted valve analysis.

It is essential that the factors leading to bioprosthetic valve dysfunction are fully understood if a more durable bioprosthesis is to be developed and the incidence of premature failure reduced. Studies of explanted bioprostheses yield important information on both the aetiology of valve failure and influence of valve/host interactions. Details are given of the Sheffield Explant Study which holds data on 570 explants and 34 different models. Advantages and disadvantages of this type of study are discussed.     

A new, non-toxic, curing agent for synthetic polyolefins.

The purpose of this study was to investigate benzocyclobutene (BCB) derivatives as non-toxic curing agents to replace accelerated sulfur systems in certain synthetic biomedical materials. Prototype artificial spinal discs have been made and implanted in a few patients from a carbon black-filled copolymer of 1-hexene and 5-methyl-1,4-hexadiene (MHD), which is sulfur cured. The polymers investigated in this study were composed of 1-hexene, allyl-BCB, and MHD (or 7-methyl-1,6-octadiene, MOD). Curing was effected through reactions on BCB, forming carbon-carbon crosslinks. Preliminary cytotoxicity tests showed the material to be non-toxic, and the physical and mechanical properties of the BCB-cured materials were comparable with those of the sulfur-cured polymers.     

Immunobiological activities of synthetic lipid A analogs with low endotoxicity.

Synthetic lipid A analogs, beta(1-6)glucosamine disaccharide 1,4'-bisphosphates, which possesses four tetradecanoyl groups at the 2- and 2'-amino, and 3- and 3'-hydroxyl groups (LA-17-PP), and each two of the (R)-3-hydroxytetradecanoyl and tetradecanoyl groups at the 2- and 2'-amino and 3- and 3'-hydroxyl groups, respectively (LA-18-PP), were far less endotoxic than synthetic (506, LA-15-PP) and bacterial Escherichia coli type lipid A's; neither compound showed any detectable lethal toxicity in chicken embryos or preparatory activity for the local Shwartzman reaction in rabbits. Also both compounds were only weakly pyrogenic and comparably less lethally toxic in galactosamine-loaded mice than the reference synthetic and bacterial lipid A's and a synthetic counterpart to biosynthetic lipid A precursor Ia (406, LA-14-PP). Nevertheless, LA-17-PP and LA-18-PP exhibited definite in vivo immunoadjuvant activity in mice, and the ability to induce a possible tumor necrosis factor and alpha/beta interferon in Mycobacterium bovis BCG and Propionibacterium acnes-primed mice, respectively, although these activities were weaker than those of the reference lipid A's. 4'-Monophosphate analogs of the above two test compounds exhibited neither endotoxic nor beneficial activities, but they showed remarkable in vitro bioactivities comparable to those of the corresponding bisphosphate compounds; the ability to activate the human complement system and the clotting enzyme cascade of horseshoe crab amoebocyte lysate, stimulatory effects on guinea pig and murine peritoneal macrophages, and murine splenocytes.     

Clefted bicuspid aortic valve.

We report an unusual case of bicuspid aortic valve in a 67-year-old man who had aortic valve replacement for combined severe aortic stenosis with moderate aortic regurgitation. Both preoperative echocardiography and angiocardiography failed to recognize the bicuspid nature of the aortic valve, which was discovered only at surgical pathology examination. The atypical anatomic findings of the valve consisted of a "cleft-like" appearance of the ventral leaflet formed by the two conjoined cusps together with a fenestrated rudimental raphe.     

Mitogenic activities of synthetic Escherichia coli lipid A and a synthetic partial structure (tripalmitoyl pentapeptide) of E. coli lipoprotein.

Synthetic Escherichia coli lipid A and synthetic S-[2,3-bis-(palmitoyloxy)propyl]-N-palmitoylpentapeptide (tripalmitoyl pentapeptide [TPP]), representing the mitogenically active principles of bacterial lipopolysaccharide (LPS) and lipoprotein, respectively, were compared for their mitogenic activities on splenocytes of LPS responder (BALB/c) and LPS-low-responder (C3H/HeJ) mice. Whereas lipid A was active only in LPS-responder mice, TPP resulted in mitogenic activation of B lymphocytes from both LPS-responder and LPS-low-responder mice. When the mitogens were added simultaneously, mainly additive effects of both activators were observed. The data suggest that two different B-lymphocyte populations are responding to these two mitogens.