29 results about "Heart transplants" patented technology

The invention features methods for the treatment of a cardiovascular disease using a polypeptide containing an extracellular ActRII variant, such as an ActRIIA variant, ActRIIB variant, or ActRII chimera. The polypeptide may include an extracellular ActRII variant fused to an Fc domain monomer. Treatment of a cardiovascular disease with a polypeptide described herein may reduce fibrosis, reduce inflammation, reduce cardiac remodeling, improve cardiac function, improve ventricular function, or slow or inhibit disease progression, which may reduce or delay the need for coronary revascularization, heart valve repair or replacement, implantation of a cardioverter-defibrillator, cardiac resynchronization therapy, a ventricular assist device, or a heart transplant.

The present invention discloses the use of CSF1-CD47 in the preparation of an early transplantation immune rejection inhibitor. The inventors have found that CSF1 / CD47 NVs can specifically bind to the corresponding ligands CSF1R and SIRPα expressed by macrophages, and on the one hand, promote bone marrow-derived monocytes to Ly6G by enhancing the CSF1 / CSF1R signaling pathway. ‑ Ly6C ‑ On the other hand, it inhibits macrophage differentiation by inhibiting macrophage phagocytosis of nanovesicles by enhancing the CD47 / SIRPα signaling pathway, prolonging the action time of CSF1, and also inhibiting the phagocytosis and antigen presentation of mononuclear macrophages to transplant antigens. In the in vivo mouse heart transplant model, CSF1 / CD47 NVs also showed more significant effects than single-target NVs in alleviating immune rejection and prolonging the survival curve of transplanted hearts. The combined use of CSF1 / CD47 can effectively alleviate early immune rejection of transplantation and improve the success rate of organ transplantation.

The invention discloses application of CPI-203 in preparation of a product for preventing and treating cardiac transplantation chronic rejection, and belongs to the technical field of biological medicine. The CPI-203 disclosed by the invention can be applied to preparation of medicines for preventing and treating chronic rejection of heart transplantation. Meanwhile, according to the experimental result, the CPI-203 can obviously prolong the survival time of the graft and reduce fibrosis and M2 cell infiltration, and the safety is superior to that of a traditional scheme. The strategy not only provides an innovative therapy for heart transplantation chronic rejection, but also opens up a new direction for transplantation of other organs and treatment of fibrosis diseases.

A hemodynamic flow assist device includes a miniature pump, a basket-like cage enclosing and supporting the pump, and a motor to drive the pump. The device is implanted and retrieved in a minimally invasive manner via percutaneous access to a patient's artery. The device has a first, collapsed configuration to assist in implantation and a second, expanded configuration once deployed and active. The device is deployed within a patient's aorta and is secured in place via a self-expanding cage which engages the inner wall of the aorta. The device includes a helical screw pump with self-expanding blades, sensors, and anchoring structures. Also disclosed is a retrieval device to remove the hemodynamic flow assist device once it is no longer needed by the patient and an arterial closure device to close the artery access point after implantation and removal of the hemodynamic flow assist device. The hemodynamic flow assist device helps to increase blood flow in patients suffering from congestive heart failure and awaiting heart transplant.

A method for performing a robotic-assisted orthotopic heart transplant includes forming a working port subareolarly by a mini-thoracotomy at a working intercostal space, forming additional ports for robotic arms, and arranging robotic arms through the ports. A first robotic arm with first forceps extends through a second port lateral to a mid-clavicular line, while second and third robotic arms containing an imaging device and second forceps operate through the working port. A fourth robotic arm with scissors or needle holder extends through a third port proximal to an anterior axillary line. The method includes cannulating for cardiopulmonary bypass, opening the pericardium, cross-clamping the aorta, removing the native heart, and performing sequential anastomoses of the donor heart including the left atrium, pulmonary artery, aorta, inferior vena cava, and superior vena cava.

The application discloses an application of niclosamide in treating organ transplant rejection. The application discloses that niclosamide can specifically interfere with the TMEM16F-CLIC1 interaction, thereby inhibiting the uptake of donor EVs by DCs, prolonging the survival time of a heart transplant by interfering with the 'costume change' of recipient DCs and inhibiting T cell activation, and indicating a new use of niclosamide in transplant immunoregulation.

Development of de novo donor specific antibodies (dnDSA) and antibody mediated rejection (AMR) remain to be a barrier for long term graft and patient survival. Most dnDSA are against mismatched donor HLA-DQ antigens. New methods for evaluating HLA-DQ mismatches are provided based on assessment of compositions and locations of categorical amino acid mismatched epitope (CAME). Specifically, amino acid residues of the HLA-DQ protein can be categorized into four groups, and categorical mismatched peptides are ranked in terms of likelihood of presentation by the recipient HLA-DRB1. Applicant has discovered the presence of DQB1 mismatches with %Ranking score ≤1 (corresponding to a binding strength between mismatched DQB1 and DQR1 between donor and recipient being in top 1%) is associated with development of dnDSA in heart transplant recipients, and dnDSA increases the risk of AMR only in recipients who have DQ mismatches with %Ranking score ≤ 1.

A cardioplegic solution composition containing coenzyme Q10, and a use thereof. the cardioplegic solution composition containing coenzyme Q10 comprising a coenzyme Q10 solution and a cardioplegic solution. In the coenzyme Q10 solution, the solvent comprises 33-60 parts by weight of a pharmaceutically acceptable polyoxyethylene nonionic surfactant and 40-67 parts by weight of a water-soluble polyhydroxy compound; the concentration of coenzyme Q10 is 14.8-58.8 μg / mg, and the obtained solution is a clear solution having an HLB value of 9-29. The cardioplegic solution composition containing coenzyme Q10 is used for the preservation of an ex vivo donor heart in heart transplantation, and and is also used in a cardioplegic solution drug for perfusion during establishment of extracorporeal circulation.

The invention provides a heart transplantation nutrition prognosis analysis system for a patient with dilated cardiomyopathy, three factors including prealbumin (PA), total bile acid (TBA) and NRS2002 score are incorporated into the analysis system, a corresponding algorithm is provided, and based on the algorithm, the optimal cutoff value of an undesirable outcome is predicted to be 0.121, the sensitivity is 72.9%, the specificity is 92.9%, and the area under a ROC curve (AUC) is 0.885 (95% CI: 0.802-0.967); when the absolute error of a calibration curve is 0.049, the HL goodness of fit test is equal to 6.134 (P is equal to 0.632 gt, 0.05), the net income threshold probability of DCA is 0.04-0.94, and the threshold probability of CIC is greater than 0.50, the prediction is highly consistent with the actual outcome. Meanwhile, the AUC value of the algorithm is obviously larger than that of other existing prediction methods, the algorithm can serve as a reliable tool for evaluating the postoperative adverse outcome risk of the patient in clinical practice, an important reference basis is provided for optimizing the individualized treatment strategy of the patient to be transplanted and perfecting the organ distribution scheme, and the accuracy and rationality of heart transplantation diagnosis and treatment can be improved.

The invention discloses a connector device for rapid suspension and lossless fixation of aorta in heart transplantation, and relates to the technical field of heart transfer equipment, the connector device comprises a connector main body, the connector main body comprises an aorta connector, and a clamping mechanism is arranged on the circumferential side of the aorta connector; the clamping mechanism comprises a fixing ring, a conical barrel and a plurality of wedge-shaped clamping jaws. Through the arrangement of the aorta connector, the clamping mechanism, the flexible parts and the like, the multiple wedge-shaped clamping jaws clamp and fix the aorta blood vessel wall through axial movement of the conical barrel, the multiple flexible parts make direct contact with the aorta blood vessel wall and wrap the aorta blood vessel wall, damage to the aorta blood vessel wall due to hard contact is avoided, and the aorta blood vessel wall is protected; and compared with a purse-string suture mode, the device has the advantages of stable circumferential clamping force and short operation time.

The invention discloses application of tazeostat in preparation of a medicine for preventing and treating cardiac transplantation chronic rejection, and belongs to the technical field of biological medicine. The medicine reduces the trimethylation level of histone H3 around a B cell p21 gene at a lysine 27 site through epigenetic regulation, relieves epigenetic inhibition on the p21 gene to highly express p21 molecules, influences differentiation of the B cell to a hair growth center B cell and plasma cells, and further relieves antibody-mediated rejection reaction, so that the survival time of a graft is remarkably prolonged, and the survival rate of the graft is improved. The function of the transplanted heart is improved.

The invention relates to the technical field of medical image processing and artificial intelligence analysis, in particular to a mechanical perfusion heart coronary artery recognition and flow velocity estimation method based on laser speckle imaging, and is suitable for donor heart function evaluation and organ quality screening before heart transplantation. Comprising the following steps: continuously imaging the surface of an isolated heart in a mechanical perfusion state to acquire a dynamic speckle image sequence, inputting the dynamic speckle image sequence into a wavelet enhancement nnU-Net model to generate a coronary artery segmentation mask, and applying the coronary artery segmentation mask to the dynamic speckle image sequence to extract image data only containing a coronary artery region, and then generating a blood flow index map, analyzing the periodic change of the blood flow index in the coronary artery region to construct a blood flow velocity change curve, and estimating the hemodynamic parameters of the coronary artery. According to the application, automatic coronary artery identification and quantitative estimation of the blood flow velocity can be carried out on the mechanically perfused isolated heart, so that rapid and accurate non-invasive evaluation on the coronary artery system of the donor heart before heart transplantation is realized.

The present invention provides, among other things, methods of using IL-2 fusion proteins, comprising an IL-2 variant and an Pc region, to treat and / or prevent heart transplant rejections. Methods of treating heart disease or a symptom thereof, conditioning a subject for heart transplant, modulating immunosuppression, and selectively increasing regulatory T cells are also disclosed.

The invention features methods for the treatment of a cardiovascular disease using a polypeptide containing an extracellular ActRII variant, such as an ActRIIA variant, ActRIIB variant, or ActRII chimera. The polypeptide may include an extracellular ActRII variant fused to an Fc domain monomer. Treatment of a cardiovascular disease with a polypeptide described herein may reduce fibrosis, reduce inflammation, reduce cardiac remodeling, improve cardiac function, improve ventricular function, or slow or inhibit disease progression, which may reduce or delay the need for coronary revascularization, heart valve repair or replacement, implantation of a cardioverter-defibrillator, cardiac resynchronization therapy, a ventricular assist device, or a heart transplant.

The invention provides application of bacteroides simplex derived outer membrane vesicles in acute rejection of heart transplantation, and belongs to the technical field of biological medicines. According to the application of the bacteroides simplex-derived outer membrane vesicles in preparation of the medicine for preventing or treating heart transplantation rejection reaction, the immune level of the transplantation position after organ transplantation is adjusted by introducing the intestinal microorganism-derived extracellular vesicles, and the problem that the toxic and side effects are remarkable after an immunosuppressive agent is used for a long time is solved; and a new thought is provided for development of immunosuppressants.

The present invention relates to a transplanted heart left atrium trimming measuring device and a method of using the same, comprising an elliptical measuring plate and an operating rod vertically passing through the measuring plate, an adjusting airbag connected to the edge of the measuring plate, a sealed air-filled cavity formed between the adjusting airbag and the measuring plate, one end of the operating rod passing through the adjusting airbag and connected to a positioning airbag, a hand-pinch airbag provided at the other end of the operating rod, a vent groove provided inside the operating rod, a vent hole provided on a section of the operating rod inside the adjusting airbag, the hand-pinch airbag, the positioning airbag and the adjusting airbag being interconnected through the vent groove and the vent hole, and a one-way air inlet valve provided on the hand-pinch airbag. The present invention is used for trimming the left atrium of a transplanted heart before a heart transplant operation, and can measure and mark the size of the incision and the amount of tissue removed as needed, thereby ensuring accurate trimming and reducing the difficulty of operation.

The present invention discloses a cardiac assist device, including a catheter and a plurality of support leaves, each of which includes a shell and a flexible bag, the flexible bag is connected to a medium extraction device through a connecting tube, the flexible bag is installed on the shell, and after the medium is injected, the flexible bag can expand and at least partially expose outside the shell; it also includes a guide mechanism and a pushing mechanism, the guide mechanism is used to guide the catheter to insert into the pericardium, the pushing mechanism can drive each of the support leaves to move along the catheter and extend out of the catheter, the shell is made of memory alloy, and in the extended state, each of the support leaves can be unfolded to cover the heart or a specific ventricle. The cardiac assist device provided by the present invention can assist the heart or a specific ventricle to beat, and can further provide auxiliary treatment for patients with heart failure to buy time for heart transplantation.

A perivascular valve device includes a valve body and define an integral tubular blood outlet passageway sidestem extending perpendicularly from said valve body, the outlet passageway being continuous with a lumen of the blood vessel, wherein the perivascular valve is selectively positional, such that the perivascular valve with sidestem can be positioned at any anatomically available level and rotational angle along the blood vessel. The outlet passageway can have a driven polymeric tongue having an upturned front end configured as a blood outflow diversion chute which is extendable a controllable distance into the lumen of the blood vessel so as to draw off a controllable volume of blood between zero and one hundred percent into said passageway for discharge through the outlet passageway sidestem. The valve body comprises a stretchable material comprising expandable furrows to allow radial expansion of the perivascular valve so as to accommodate growth in pediatric patients.

The invention discloses an application method of a Mongolian medicine compound preparation in isolated cold preservation of heart, and relates to the technical field of heart preservation, comprising a dose-effect experiment process and an animal experiment process; the dose-effect experiment process comprises the following steps: testing the influence of choerospondium-7 pills with different concentrations on the isolated heart, carrying out multi-channel electric marking on the heart, recording field potential and electric signals under stimulation, and determining the optimal onset concentration; the animal experiment process comprises the following steps: step 1, animal isolated heart modeling and grouping (the isolated heart is stored in UW liquid for 8 hours and stored in UW liquid and Mongolian medicine for 8 hours), step 2, animal isolated heart stimulation and position mapping, and step 3, index recording and data acquisition. The cold preservation liquid can be optimized, damage caused by cold preservation is reduced, the preservation effect of the donor heart is improved, the treatment effect of heart transplantation is improved to the maximum extent, ischemic myocardial damage is reduced to the maximum extent, and the isolated heart function is maintained.

The application discloses application of 5'-AMP monohydrate in preparation of a medicine for treating cold preservation injury of a heart transplant donor heart, and provides a technical scheme, in which a core mechanism of cold preservation time-dependent myocardial injury is revealed through cross-species multi-omics joint analysis, and a cascade network of "metabolic imbalance-lactate modification disorder and inflammation activation-mitochondrial injury" is constructed. Metabolomics analysis shows that glycolysis-TCA cycle coupling imbalance is characterized by decrease of lactic acid and accumulation of NADH, and up-regulation of LDHB expression drives the change of metabolic preference from lactic acid generation to consumption. The metabolic reconstruction not only leads to depletion of the lactic acid pool, but also forms a vicious cycle through imbalance of NADH / NAD+ redox ratio. Based on the above mechanism, the research successfully screens out a high-efficiency small-molecule inhibitor Adenosine 5'-monophosphate monohydrate (5'-AMP monohydrate) targeting LDHB for the first time. The compound plays a protective effect by inhibiting LDHB activity: can effectively reduce NADH accumulation while maintaining lactic acid metabolic homeostasis, and enhance the stability of mitochondrial structure.

The invention discloses application of RG108 in heart transplantation immunosuppression by regulating T cell functions, and relates to the technical field of medical bioengineering. The invention innovatively provides a method for inhibiting the activity of DNA methyltransferase 1 (DNMT1) by using a small molecule compound RG108, and by reducing the methylation level of a CDKN1A gene promoter, restoring the expression of the promoter and inducing T cells to enter an aging state, the proliferation and effect activity of the promoter is reduced, and rejection reaction is inhibited. The RG108 is a non-nucleoside DNMT1 selective inhibitor with a clear structure, the activity of the inhibitor is inhibited by combining with a catalytic structural domain, DNA is not doped, off-target toxicity is not caused, and the RG108 is an ideal molecule for realizing controllable and reversible epigenetic regulation. A new transplantation immune tolerance strategy is established, and the defects that an existing immunosuppressor is large in side effect and cannot induce immune memory tolerance are overcome.

The invention provides a sterilizing solution, and a pretreatment method and a preservation method of a same valved pipeline, and belongs to the technical field of medical treatment. The invention provides a sterilizing solution which takes TCM199 as a solvent and comprises the following components: third-generation cephalosporin, amphotericin B, polypeptide antibiotics and aminoglycoside antibiotics. The sterilizing solution disclosed by the invention is reasonably compounded, and has the advantages of protecting the activity of a valvular canal and avoiding transplantation-related infectious endocarditis. The invention further provides a pretreatment method of the allogeneic valvular ducts, different treatment methods are adopted for the allogeneic valvular ducts from donors with different death times or heart transplantation times through a classification and time period division method, transplantation related infection is avoided, and meanwhile the treatment efficiency is improved. And the activity of the allogeneic valved pipeline can be protected as much as possible.

The invention provides application of parabacteroides dielsii-derived outer membrane vesicles in acute rejection of heart transplantation, and belongs to the technical field of biological medicines. The invention provides the application of the outer membrane vesicles derived from the parabacteroides dieldrii in preparation of the medicine for relieving acute rejection of heart transplantation, and the outer membrane vesicles derived from the parabacteroides dieldrii have good biocompatibility and immune negative regulation capability, can effectively relieve acute rejection of organ transplantation immune, and can be used for preparing the medicine for relieving acute rejection of heart transplantation. The toxic and side effects caused by long-term use of the immunosuppressor are reduced, a new thought and scheme are provided for the development of the novel immunosuppressor, and the application prospect is wide.

The invention discloses an application of a GSDMD molecular inhibitor NU6300 in preparation of a medicine for treating heart transplantation rejection. The GSDMD molecular inhibitor NU6300 is applied to a constructed heart transplantation model, and after treatment of the GSDMD molecular inhibitor NU6300, it is observed that the survival time of heart grafts of an experimental group and a control group is prolonged, the GSDMD-mediated pyroptosis level is reduced, and the infiltration degree of inflammatory cytokines in the grafts is weakened. Therefore, the invention can provide a new therapeutic drug for treating patients after organ transplantation, and can be applied to organ transplantation treatment.

The invention discloses an application of 5 '-AMP monophosphate in preparation of a medicine for treating heart transplantation donor heart cold preservation injury, in the technical scheme provided by the invention, through cross-species multi-omics conjoint analysis, a core mechanism of cold preservation time dependent myocardial injury is disclosed, and the application of 5'-AMP monophosphate in preparation of a medicine for treating heart transplantation donor heart cold preservation injury is provided. And a cascade network of metabolic imbalance-lactylation modification disorder and inflammation activation-mitochondrial injury is constructed. Metabonomics analysis shows that glycolysis-TCA cycle coupling imbalance is characterized by lactic acid decrease and NADH accumulation, and LDHB expression up-regulation drives the metabolism preference to be converted from lactic acid generation to consumption. The metabolic reconstitution not only leads to depletion of the lactic acid pool, but also forms vicious circle through NADH / NAD + redox proportion imbalance. On the basis of the mechanism, the research successfully screens out an efficient small-molecule inhibitor Adenosine 5 '-monophosphate (5'-AMP monophosphate) of the targeted LDHB for the first time, and the efficient small-molecule inhibitor Adenosine 5 '-monophosphate (5'-AMP monophosphate) of the targeted LDHB can be used for inhibiting the LDHB. The compound exerts a protection effect by inhibiting LDHB activity: NADH accumulation can be effectively reduced, the stable state of lactic acid metabolism is maintained, and the mitochondrial structure stability is enhanced.

Gene expression is measured in a sample of peripheral blood mononuclear cells (PBMCs) obtained from a subject and used to predict organ function recovery. A Function Recovery Potential (FRP) score is assigned to a sample that reflects the measured expression level of the genes identified herein in a direction associated with recovery from organ failure. Treatment of the subject with optimal medical management (OMM) and / or palliative care (PC) is advised when the FRP score is lower than the reference value, and referring the subject for treatment with therapies including - but not limited to - mechanical circulatory support (MCS) surgery, heart transplant (HTx) surgery, or other intervention for advanced heart failure is advised when the FRP score is greater than the reference value. A method for developing an FRP scoring algorithm that predicts a subject's ability to recover from medical intervention for organ failure is also described.

The present invention discloses a new application of clemastine fumarate in the preparation of a drug for treating organ transplant rejection. Research in the present invention shows that clemastine fumarate can significantly reduce the occurrence of cardiac transplant rejection, specifically by significantly prolonging the survival time of mouse heart transplants, significantly reducing the degree of acute rejection graft lesions in mice, inhibiting mouse T cell allogeneic immune response, reducing the degree of rejection damage and immune infiltration of cardiac transplants, inhibiting mouse T cell proliferation, reducing the proportion of Th1 cell subsets in mouse spleen and draining lymph nodes, reducing the IFN-γ and T-bet gene expression levels in the spleen and draining lymph nodes of recipient mice and the levels of pro-inflammatory IFN-γ, TNF-α and IL-5 cytokines in the body, etc., indicating that clemastine fumarate can be used as a new immunosuppressant for treating cardiac and other organ transplant rejection, especially acute rejection after cardiac and other organ transplants.

The invention discloses application of macrophage MHC-II molecular expression based on circadian rhythm regulation in heart transplantation, and belongs to the technical field of biological medicine. According to the method, the optimal obtaining opportunity of the donor heart is obtained through circadian rhythm synchronization, circadian rhythm molecular diagnosis and algorithm fitting and optimization, then when the donor heart is obtained, an anti-MHC-II neutralizing antibody is poured, meanwhile, the anti-MHC-II neutralizing antibody is added into a soaking preservation solution, the anti-MHC-II neutralizing antibody directly acts on the immune system of the donor, and the anti-MHC-II neutralizing antibody directly acts on the immune system of the donor. The expression level of MHC-II molecules on the surface of the macrophage is reduced. According to the method, the defects and deficiencies existing in an existing heart transplantation technology are overcome, and particularly the problems that the donor circadian rhythm is not included in a transplantation distribution system and the donor heart obtaining time cannot be effectively optimized are solved. According to the method, immunological rejection after heart transplantation can be effectively reduced, the dosage and side effects of an immunosuppressant are reduced, and meanwhile the transplantation success rate and the long-term survival rate of a patient are increased.

The invention discloses a simulation analysis system for a heart load removal state, and belongs to the technical field of medicine. The problem that simulation cannot be carried out on a small animal body in the prior art is solved, the left ventricle unloading model is creatively constructed by combining the myocardial infarction model and the heart transplantation model, the limitation that the heart unloading state cannot be simulated on the small animal body in the prior art is overcome, and the experimental group and the control group are set, so that the simulation accuracy is improved. The method can clearly compare the difference between the heart de-loading state and the normal state, is beneficial to accurately evaluating the heart de-loading effect, avoids simulation analysis deviation caused by individual difference factors, and can accurately evaluate the heart de-loading effect by collecting the physiological and pathological data of the heart of the experimental group and the control group and combining quantitative analysis and quantitative analysis methods. The heart load removal state can be comprehensively evaluated, and a more accurate basis is provided for research and treatment of heart diseases.