Novel heart valve leaflet designs with stiff polymeric materials and biomimetic kinematics

Despite continuous efforts to improve the robustness of cardiac valve implants,neither bioprosthetic nor mechanical valves fulfill both hemodynamic and durability requirements.This study discussed novel flexible leaflet designs,focusing on polymeric materials with proven hemocompatibility,such as polyether ether ketone,of much higher stiffness than native tissue,aiming at optimal valve implants.A biomimetic valve with a single-curvature belly-curve(B-C)was used as a reference for new design variants with a double-curvature B-C with varying radii.Soft(13.2 MPa)and stiff(2.4 GPa)leaflet materials and different thicknesses were studied using lean simulations and in vitro experiments under physiologic hemodynamic conditions.The performance was assessed using opening pressure(OP)and orifice area(OA).The latter was determined by a newly developed automatized image processing tool.Experimental trends are in agreement with simulations and demonstrated that a buckling-inspired double-curvature leaflet design significantly enhances the trileaflet valve opening behavior,which is particularly advantageous for stiffer leaflet materials.Compared to the reference,the best-performing variant showed an OP improvement of 47%and 44%based on simulations and experiments,respectively.In contrast,the achieved mean pressure differential was directly comparable to state-of-the-art bioprosthetic valves.The OA was slightly reduced for new variants but still in the satisfying range.

Need for new materials,biofunctionalization and nonsurgical heart valve technology

Transition from non-surgical heart valve defects repair from bench to bedside is a reality.Some biological material-based designs for transcatheter aortic valve implantation are ready for use.Their drawback,however is their unknown functional as well as structural durability.Moreover,research on new non-biological materials is essential to replace classical animal-derived sources of human heart valve prostheses.

A comprehensive review of cavitation in valves:mechanical heart valves and control valves

Valves are widely used in various working conditions for their flow control functions,and the cavitation inside valves has been investigated owing to its harm to the valve itself and the connecting downstream parts.This paper presents a comprehensive review of the progress that has been achieved in the past years about cavitation in valves including both mechanical heart valves and control valves.The review is divided in the following parts,namely the location where there is a high possibility of the occurrence of cavitation,the parameters that affect cavitation intensity,and the methods to minimize cavitation intensity.It should be noticed that although simulation has been widely used,advanced experiments are still needed in order to obtain accurate analysis of cavitation in valves and the cavitation model still needs to be improved.

Large-Scale Surface Modification of Decellularized Matrix with Erythrocyte Membrane for Promoting In Situ Regeneration of Heart Valve

In situ regeneration is a promising strategy for constructing tissue engineering heart valves(TEHVs).Currently,the decellularized heart valve(DHV)is extensively employed as a TEHV scaffold.Nevertheless,DHV exhibits limited blood compatibility and notable difficulties in endothelialization,resulting in thrombosis and graft failure.The red blood cell membrane(RBCM)exhibits excellent biocompatibility and prolonged circulation stability and is extensively applied in the camouflage of nanoparticles for drug delivery;however,there is no report on its application for large-scale modification of decellularized extracellular matrix(ECM).For the first time,we utilized a layer-by-layer assembling strategy to immobilize RBCM on the surface of DHV and construct an innovative TEHV scaffold.Our findings demonstrated that the scaffold significantly improved the hemocompatibility of DHV by effectively preventing plasma protein adsorption,activated platelet adhesion,and erythrocyte aggregation,and induced macrophage polarization toward the M2 phenotype in vitro.Moreover,RBCM modification significantly enhanced the mechanical properties and enzymatic stability of DHV.The rat models of subcutaneous embedding and abdominal aorta implantation showed that the scaffold regulated the polarization of macrophages into the anti-inflammatory and pro-modeling M2 phenotype and promoted endothelialization and ECM remodeling in the early stage without thrombosis and calcification.The novel TEHV exhibits excellent performance and can overcome the limitations of commonly used clinical prostheses.

Univariate Risk Factors for Prolonged Mechanical Ventilation in Patients Undergoing Prosthetic Heart Valves Replacement Surgery

Data from 736 patients undergoing prosthetic heart valve replacement surgery and concomitant surgery （combined surgery） from January 1998 to January 2004 at Union Hospital were retrospectively reviewed. Univariate logistic regression analyses were conducted to identity risk factors for prolonged mechanical ventilation. The results showed that prolonged cardiopulmonary bypass duration, prolonged aortic cross clamp time and low ejection fraction less than 50 percent （50 %） were found to be independent predictors for prolonged mechanical ventilation. Meanwhile age, weight, and preoperative hospital stay （days） were not found to be associated with prolonged mechanical ventilation. It was concluded that. for age and weight, this might be due to the lower number of old age patients （70 years and above） included in our study and genetic body structure of majority Chinese population that favor them to be in normal weight, respectively.

Management dilemmas in patients with mechanical heart valves and warfarin-induced major bleeding

Management of warfarin-induced major bleeding in patients with mechanical heart valves is challenging. There is vast controversy and confusion in the type of treatment required to reverse anticoagulation and stop bleeding as well as the ideal time to restart warfarin therapy safely without recurrence of bleeding and/or thromboembolism. Presently, the treatments available to reverse warfarin-induced bleeding are vitamin K, fresh frozen plasma, prothrombin complex concentrates and recombinant activated factor VIIa. Currently, vitamin K and fresh frozen plasma are the recommended treatments in patients with mechanical heart valves and warfarin-induced major bleeding. The safe use of prothrombin complex concentrates and recombinant activated factor VIIa in patients with mechanical heart valves is controversial and needs well-designed clinical studies. With regard to restarting anticoagulation in patients with warfarin-induced major bleeding and mechanical heart valves, the safe period varies from 7-14 d after the onset of bleeding for patients with intracranial bleed and 48-72 h for patients with extra-cranial bleed. In this review article, we present relevant literature about these controversies and suggest recommendations for management of patients with warfarin-induced bleeding and a mechanical heart valve. Furthermore, there is an urgent need for separate specific guidelines from major associations/ professional societies with regard to mechanical heart valves and warfarin-induced bleeding.

Preparation of gradient biomaterial used for artificial mechanical heart valve

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The Application Effect of Predictive Nursing on Cardiopulmonary Rehabilitation of Patients Undergoing Heart Valve Surgery with Extracorporeal Circulation

Objective:To evaluate the application effect of predictive nursing on patients undergoing heart valve surgery with extracorporeal circulation(ECC).Methods:92 ECC patients admitted to the hospital between July 2021 and July 2023 were selected and grouped by random number table method;the observation group practiced predictive nursing,while the reference group practiced conventional nursing.The cardiopulmonary rehabilitation and other indexes were compared between the groups.Results:The postoperative rehabilitation time of the observation group was shorter than that of the reference group,the treatment compliance was higher than that of the reference group,the cardiopulmonary function indexes were all better than that of the reference group,and the complication rate was lower than that of the reference group(P<0.05).Conclusion:The implementation of predictive nursing for ECC patients can promote postoperative rehabilitation,improve patients’treatment compliance,and enhance the cardiopulmonary rehabilitation effect,and nursing safety is high.

Pathogenic Mineralization of Calcium Phosphate on Human Heart Valves

When calcium phosphate forms in soft tissues such as blood vessels and heart valves, it causes disease. The abnormal formation of calcium phosphate is called pathogenic mineralization or pathogenic calcification. Cases of rheumatic heart disease （RHD） always occur with fibrotic and calcified tissue of heart valve. In this article, samples taken from calcified human heart wdves were studied. The characterization was performend by scanning electronic microscope, X-ray Diffraction and transmission electron microscopy with selective diffraction patterns. It is found for the first time that calcium phosphate grains existing in the calcified human heart valves contain octacalcium phosphate （ OCP ）.

DETECTION OF PRIMARY TISSUE FAILURE POTENTIAL OF BIOPROSTHETIC HEART VALVES IN A STERILE PULSE DUPLICATOR SYSTEM

This paper discusses results of anatomic analogy and transmission line model for designing a sterile pulse duplication system for bioprostheses. By simulating physiological flow and pressure pulses as well as the input impedance of the human arterial system Pulsatile function testing allows us to study the hydrodynamic performances and the leaflet action of each valve. This inspection enables us to identify and reject those valves exhibiting leaflet prolapse or lazy leaflet or others believed to contribute to Primary tissue failure. Consequently, the risk of valve complications is reduced

In vitro calcification studies on bioprosthetic and decellularized heart valves under quasi-physiological flow conditions

The lifespan of biological heart valve prostheses available in the market is limited due to structural alterations caused by calcium phosphate deposits formed from blood plasma in contact with the tissues.The objective of this work is to present a comparative methodology for the investigation of the formation of calcium phosphate deposits on bioprosthetic and tissue-engineered scaffolds in vitro and the influence of mechanical forces on tissue mineralization.Based on earlier investigations on biological mineralization at constant supersaturation,a circulatory loop simulating dynamic blood flow and physiological pressure conditions was developed.The system was appropriately adapted to evaluate the calcification potential of decellularized(DCV)and glutaraldehyde-fixed(GAV)porcine aortic valves.Results indicated that DCV calcified at higher,statistically nonsignificant,rates in comparison with GAV.This difference was attributed to the tissue surface modifications and cell debris leftovers from the decellularization process.Morphological analysis of the solids deposited after 20 h by scanning electron microscopy in combination with chemical microanalysis electron-dispersive spectroscopy identified the solid formed as octacalcium phosphate(Ca8(PO4)6H2·5H2O,OCP).OCP crystallites were preferentially deposited in high mechanical stress areas of the test tissues.Moreover,GAV tissues developed a significant transvalvular pressure gradient increase past 36 h with a calcium deposition distribution similar to the one found in explanted prostheses.In conclusion,the presented in vitro circulatory model serves as a valuable prescreening methodology for the investigation of the calcification process of bioprosthetic and tissue-engineered valves under physiological mechanical load.

Imaging of pannus formation in patients with mechanical heart valves

Patient-prosthesis mismatch(PPM) should be recognized in patients with elevated transprosthetic gradients but without leaflet immobility, since the treatment strategy may differ in either etiology. However, thrombus and/or pannus formation should be excluded before a diagnosis of PPM is made. Particularly, pannus formation may not be diagnosed with 2-dimensional transesophageal echocardiography. Electrocardiographically gated 64-section multidetector computed tomography(MDCT) may be a promising tool in diagnosing or excluding pannus formation. Our report underlines the utility of MDCT in this regard and also emphasizes the importance of recognition of PPM as a differential diagnosis in such patients.

Comparative Study of Different Materials with Al-Sic for Engine Valve Guide by Using FEM

In this work, an effort has been designed to raise the reliability of engine using Al-Sic composites with other alternatively materials for the engine valve guides. Aluminum matrix composites have found the most suitable inside automotive, aerospace and aircraft industries and contain the greatest promise for future year’s growth. The finite element analysis of the Al-Sic composite with Titanium alloy (Ti-834), Copper Nickel Silicon alloys (CuNi3Si), and aluminum bronze alloy as an alternative material for engine valve guide was done using Ansys 13.0 software. The stress analysis of engine valve guide under the different pressure and temperature is considered, the pressure is taken as from 10 MPa to 100 MPa with different temperatures varying from 600℃ to 650℃. The temperature, principal stress and principal strain distribution on the entire surface area of the engine valve guide were obtained. The stresses were observed to be well below the permitted stress for all the materials but the Al-Sic composites found the most suitable one. Valve guide is modeled in pro-engineer software and analysis is carried out in Ansys 13.0. The deformations and stresses induced due to structural and thermal loading is illustrated and discussed.

Expression of matrix metalloproteinase-9 was effected by epoxy chloropropan on creating tissue engineered heart valves

Objectives To investigate the effects of epoxy chloropropan on the expression of matrix metalloproteinases-9 （MMP-9）in creating tissue engineered heart valves（TEHV）,on the tissue structures of TEHV,and to study the effects of epoxy chloropropan on the calcification of TEHV.Methods The porcine aortic valve leaflets were digested and decellularized by using detergent and trypsin.Those treated with 0.3% glutaraldehyde for 48 hours were the control group;those treated with 3% epoxy choloropropan for 24 hours were the experimental group.The cultured human bone marrow mesenchymal stem cells（hBMSCs）were seeded onto the decellularized scaffolds of TEHV.The histological studies were done with pathological sections and scanning electron microscopy and reverse transcriptase-polymerase chain reaction（RT-PCR）were used to detect the expression of MMP-9.Results In the experimental group.the histology showed that the BMSCs grew well into the pores and formed a confluent layer in decellularized scaffolds;RT-PCR indicated significantly attenuated expressions of MMP-9,compared with the control（P〈0.05）.Conclusion The decellularized porcine aortic valves treated with 3% epoxy chloropropan may inhibit the expression of MMP-9;therefore epoxy chloropropan may prevent the calcification of tissue engineered heart valves.

Low-intensity anticoagulation therapy in the pregnant women with mechanical heart valves:a report with 56 cases

Objective To evaluate the method of low-intensity anticoagulation therapy in the pregnant women who had received mechanical heart valve replacemant,and the effects of warfarin on the pregnant women and their fetus. Methods This retrospective study involved 56 pregnant women (61 pregnancies) who had received mechanical heart valve replacement. Their pregnant status,delivery, and anticoagulation therapy were observed

Application of Decellularized Scaffold Combined with Loaded Nanoparticles for Heart Valve Tissue Engineering in vitro

The purpose of this study was to fabricate decelluarized valve scaffold modified with polyethylene glycol nanoparticles loaded with transforming growth factor-β1（TGF-β1）,by which to improve the extracellular matrix microenvironment for heart valve tissue engineering in vitro.Polyethylene glycol nanoparticles were obtained by an emulsion-crosslinking method,and their morphology was observed under a scanning electron microscope.Decelluarized valve scaffolds,prepared by using trypsinase and TritonX-100,were modified with nanoparticles by carbodiimide,and then TGF-β1 was loaded into them by adsorption.The TGF-β1 delivery of the fabricated scaffold was measured by asing enzyme-linked immunosorbent assay.Whether unseeded or reseeded with myofibroblast from rats,the morphologic,biochemical and biomechanical characteristics of hybrid scaffolds were tested and compared with decelluarized scaffolds under the same conditions.The enzyme-linked immunosorbent assay revealed a typical delivery of nanoparticles.The morphologic observations and biological data analysis indicated that fabricated scaffolds possessed advantageous biocompatibility and biomechanical property beyond decelluarized scaffolds.Altogether this study proved that it was feasible to fabricate the hybrid scaffold and effective to improve extracellular matrix microenvironment,which is beneficial for an application in heart valve tissue engineering.

Trilayer anisotropic structure versus randomly oriented structure in heart valve leaflet tissue engineering

It has been hypothesized that leaflet substrates with a trilayer structure and anisotropicmechanical properties could be useful for the production of functional and long-lasting tissue-engineered leaflets.To investigate the influence of the anisotropic structural and mechanical characteristics of a substrate on cells,in this study,we electrospun trilayer anisotropic fibrous substrates and randomly oriented isotropic fibrous substrates(used as controls)from polycaprolactone polymers.Consequently,the random substrates had higher radial and lower circumferential tensile properties than the trilayer substrates;however,they had similar flexural properties.Porcine valvular interstitial cells cultured on both substrates produced random and trilayer cell-cultured constructs,respectively.The trilayer cell-cultured constructs had more anisotropic mechanical properties,17%higher cellular proliferation,14%more extracellular matrix(i.e.,collagen and glycosaminoglycan)production,and superior gene and protein expression,suggesting that more cells were in a growth state in the trilayer constructs than in the random constructs.Furthermore,the random and radial layers of the trilayer constructs had more vimentin,collagen,transforming growth factor-beta 1(TGF-ß1),transforming growth factor-beta 3(TGF-ß3)gene expression than in the circumferential layer of the constructs.This study verifies that the differences in structural,tensile,and anisotropic properties of the trilayer and random substrates influence the characteristics of the cells and ECM in the constructs.

Development of High-Speed On-Of Valves and Their Applications

With the widespread application of the computer and microelectronic technology in the industry,digitization becomes the inevitable developing trend of the hydraulic technology.Digitization of the hydraulic components is critical in the digital hydraulic technology.High-speed on-of valves(HSVs)which convert a train of input pulses into the fast and accurate switching between the on and of states belong to widely used basic digital hydraulic elements.In some ways,the characteristics of the HSVs determine the performance of the digital hydraulic systems.This paper discusses the development of HSVs and their applications.First,the HSVs with innovative structures which is classifed into direct drive valves and pilot operated valves are discussed,with the emphasis on their performance.Then,an overview of HSVs with intelligent materials is presented with considering of the switching frequency and fow capacity.Finally,the applications of the HSVs are reviewed,including digital hydraulic components with the integration of the HSVs and digital hydraulic systems controlled by the HSVs.

Effect of L-carnitine on Cardiomyocyte Apoptosis and Cardiac Function in Patients Undergoing Heart Valve Replacement Operation

Summary： The effects of L-carnitine, as an ingredient of cardioplegia solution, on cardiac function and cardiomyocyte apoptosis in patients undergoing heart valve replacement operation were investigated. Twenty-three cases undergoing heart valve replacement with cardiopulmonary bypass （CPB） were randomly allocated into two groups： L-carnitine group （n=12, 12 g/L L-carnitine was put in the ST. Thomas cardioplegia） and control group （n=11, identical to the L-carnitine group except that normal saline was administered instead of L-carnitine）. Serum cardial troponin I （cTnI） levels, the left ventricular ejection fraction （LVEF）, and cardiac index （CI） were measured perioperatively. A bit of myocardial tissue obtained from right atria was taken before CPB and by the end of intracardiac procedure to undergo electron microscopy examination and estimate apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL）. From the end of CPB to 3 days after operation, the serum levels of cTnI in the L-carnitine group was significantly lower than that in the control group （P〈0.05）. Heart color ultrasonogram showed that the CI index and LVEF at 7th day postoperatively in the L-carnitine group were significantly higher than in the control group （P〈0.05）. Compared to the control group, L-carnitine significantly alleviated the morphologic changes of cardiac muscle cells （electron microscopy examination） and decreased the amounts of apoptotic cardiac muscle cells （TUNEL）. Furthermore, the dosage of vasoactive drugs used after operation was significantly less in the L-carnitine group （P〈0.01）. It was concluded that L-carnitine cardioplegia solution could improve cardiac function in patients undergoing heart valve replacement operation and alleviate CPB-mediated apoptosis of cardiac muscle cells.

Anticoagulation early after mechanical heart valve replacement

Objective： To explore the changes of coagulation activity and the characters of anticoagulation early after mechanical heart valve replacement. Methods： All patients only took warfarin orally for anticoagulation. The predicted international normalized ratio （INR） was 1.5 to 2.0. Several coagulation markers were monitored early after valve replacement. Complications associated with anticoagulation were recorded and analyzed. The patients were divided into three groups based on the number and position of mechanical valve prothesis, including group M （mitral valve replacement）, group A （aortic valve replacement） and group D （mitral and aortic valve replacement）.Comparison was made between the three groups. Results： Three events of mild cerebral embolism and five events of mild bleeding occurred during the early postoperative period. One patient suffered from mild cerebral embolism on the 4th day after operation, accompanied by large volume of pericardial drainage. Two patients with bleeding had lower INRs than predicted range. However, INR in one patient with mild cerebral embolism was in the predicted range. There was no significant difference in thrombo time （TT）, activated partial thromboplastin time （APTT） and 1NR on the 3rd day after operation compared to those before operation; meanwhile, plasma fibrinogen （FIB） concentration was higher than that before operation （P〈0.05）. 1NR had no significant changes on the 2nd day after the beginning of anticoagulation compared to that before operation; however, 1NR was significantly elevated on the 4th day （P〈0.05）. Warfarin doses and INRs were similar among the three groups, but FIB concentrations in plasma were higher in groups M and D than in group A （P〈0.01）. Conclusion： Hypercoagulabale state exists early after mechanical heart valve replacement. When anticoagulation begins is determined by the change of coagulation markers, not by the volume of chest or pericardial drainage. INR can not accurately reflect the coagulation state sometimes, especially during the first 3 days after anticoagulation. The number and position of mechanical valve prothesis could affect coagulation state. Therefore, anticoagulation therapy should be regulated accordingly.