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Image registration plays a vital role in the mosaic process of multiple UAV (Unmanned Aerial Vehicle) images acquired from different spatial positions of the same scene. Aimed at the problem that many fast registration methods cannot provide both high speed and accuracy simultaneously for UAV visible light images, this work proposes a novel registration framework based on a popular baseline registration algorithm, ORB—the Oriented FAST (Features from Accelerated Segment Test) and Rotated BRIEF (Binary Robust Independent Elemental Features) algorithm. First, the ORB algorithm is utilized to extract image feature points fast. On this basis, two bidirectional matching strategies are presented to match obtained feature points. Then, the PROSRC (Progressive Sample Consensus) algorithm is applied to remove false matches. Finally, the experiments are carried out on UAV image pairs about different scenes including urban, road, building, farmland, and forest. Compared with the original version and other state-of-the-art registration methods, the bi-matching ORB algorithm exhibits higher accuracy and faster speed without any training or prior knowledge. Meanwhile, its complexity is quite low for on-board realization. [ABSTRACT FROM AUTHOR]

Background: Corheart 6 (Corheart) is a newly developed magnetically levitated continuous‐flow left ventricular assist device currently undergoing multicenter clinical trials in China. Featuring a small size, minimal weight, and low power consumption, the Corheart aims to improve pump hemocompatibility, reduce adverse events, and enhance the quality of life of heart failure patients. Methods: Computational simulations assessed flow field, shear stress, and washout, while in vitro and in vivo experiments were performed to further demonstrate hemocompatibility. Results: Numerical results show that the flow path in the Corheart blood pump is well designed. There is no significantly high shear stress in the majority of the flow domain. Short secondary flow paths and small pump size (small priming volume) provide good washing (0.049 and 0.165 s to remove 55% and 95% old blood, respectively), allowing low hemolysis levels both in computational and in vitro hemolysis tests (in vitro hemolysis index ranges from 0.00092 ± 0.00006 g/100 L to 0.00134 ± 0.00019 g/100 L). Good hemocompatibility was further evidenced by ten 60‐day sheep implants tested with relatively low flow rates of 2.0 ± 0.2 L/min; the results showed no hemolysis or thrombosis. Conclusions: Numerical and experimental results shed light on the fluid dynamics characteristics and hemocompatibility of the Corheart. It is believed that the Corheart will provide more promising possibilities for minimally invasive implantation techniques and for those patients with a small body surface area. [ABSTRACT FROM AUTHOR]

Autoimmune demyelinating diseases can be induced by an immune response against myelin peptides; however, the exact mechanism underlying the development of such diseases remains unclear. In experimental autoimmune encephalomyelitis, we found that the clearance of exogenous myelin antigen at the peak of the primary immune response is key to the pathogenesis of the disease. The generation of effector T cells requires continuous antigen stimulation, whereas redundant antigen traps and exhausts effector T cells in the periphery, which induces resistance to the disease. Moreover, insufficient antigenic stimulation fails to induce disease efficiently owing to insufficient numbers of effector T cells. When myelin antigen is entirely cleared, the number of effector T cells reaches a peak, which facilitates infiltration of more effector T cells into the central nervous system. The peripheral antigen clearance initiates the first wave of effector T cell entry into the central nervous system and induces chronic inflammation. The inflamed central nervous system recruits the second wave of effector T cells that worsen inflammation, resulting in loss of self‐tolerance. These findings provide new insights into the mechanism underlying the development of autoimmune demyelinating diseases, which may potentially impact future treatments. [ABSTRACT FROM AUTHOR]

Objective: Cardiogenic shock (CS) often occurs in patients suffering from rapidly progressing end‐stage heart failure or acute myocardial infarction. Mechanical circulatory support may be used for patients who do not respond to medication or revascularization to stabilize hemodynamics. Extracorporeal ventricular assist device (Extra‐VAD) has been reported to be successful for patients with cardiogenic shock. This study aimed to evaluate the 30‐day in‐vivo performance and safety of a newly developed Extra‐VAD with maglev centrifugal pump technology, MoyoAssist®. Method: The study was conducted with 6 healthy ovine models, weighing 43.2 ~ 59.6 kg. Cannulation was performed with a 34 Fr venous cannula surgically connected to the left arterial appendage and a 24 Fr arterial cannula inserted into descending aorta. The pump flow rate was maintained at 2 ~ 3 L/min to provide sufficient cardiac support without suction. Activated clotting time was maintained within the range of 150 ~ 250 s. Results: No device‐related adverse events occurred throughout the study. Plasma‐free hemoglobin results were within the acceptable range of ventricular assist device therapy (<40 mg/dl). MGS01 had an anticoagulation management related bleeding event and was terminated on day 29. All other sheep's biochemical test results were stable. The autopsy showed no embolism or thrombus formation and no end‐organ damage. Conclusion: This study demonstrated that the MoyoAssist® Extra‐VAD is able to provide cardiac support effectively and safely and may provide a new alternative choice for patients with CS in China. [ABSTRACT FROM AUTHOR]

Thoracic aortic dissection (TAD) is an aortic disease associated with dysregulated extracellular matrix composition and de‐differentiation of vascular smooth muscle cells (SMCs). Growth Differentiation Factor 11 (GDF11) is a member of transforming growth factor β (TGF‐β) superfamily associated with cardiovascular diseases. The present study attempted to investigate the expression of GDF11 in TAD and its effects on aortic SMC phenotype transition. GDF11 level was found lower in the ascending thoracic aortas of TAD patients than healthy aortas. The mouse model of TAD was established by β‐aminopropionitrile monofumarate (BAPN) combined with angiotensin II (Ang II). The expression of GDF11 was also decreased in thoracic aortic tissues accompanied with increased inflammation, arteriectasis and elastin degradation in TAD mice. Administration of GDF11 mitigated these aortic lesions and improved the survival rate of mice. Exogenous GDF11 and adeno‐associated virus type 2 (AAV‐2)‐mediated GDF11 overexpression increased the expression of contractile proteins including ACTA2, SM22α and myosin heavy chain 11 (MYH11) and decreased synthetic markers including osteopontin and fibronectin 1 (FN1), indicating that GDF11 might inhibit SMC phenotype transition and maintain its contractile state. Moreover, GDF11 inhibited the production of matrix metalloproteinase (MMP)‐2, 3, 9 in aortic SMCs. The canonical TGF‐β (Smad2/3) signalling was enhanced by GDF11, while its inhibition suppressed the inhibitory effects of GDF11 on SMC de‐differentiation and MMP production in vitro. Therefore, we demonstrate that GDF11 may contribute to TAD alleviation via inhibiting inflammation and MMP activity, and promoting the transition of aortic SMCs towards a contractile phenotype, which provides a therapeutic target for TAD. [ABSTRACT FROM AUTHOR]

As a pre-clinical assessment, the present study aimed to investigate the safety and effectiveness of a novel valved pulmonary arterial conduit constructed entirely from biomaterials by transplanting it in the outflow tract of the right ventricle in sheep. Under extracorporeal circulation, the valved pulmonary arterial conduit was used to replace the pulmonary artery of sheep with a beating heart. The performance was assessed at 30, 90 and 180 days post-surgery. Hemodynamic and structural changes were evaluated, and safety was assessed after 180 postoperative days. The hemodynamic effect and biosafety of the implant were further evaluated by observing the changes in various pressure indicators of the heart, echocardiographic results, anatomical and pathological examination results, liver and kidney functions, routine blood tests, a blood coagulation test, and other test results following implantation of the purely biotic valved conduit. The conduit was successfully implanted in 12 sheep and no mortality occurred postoperatively. During the 180-day follow-up, there was no obvious stenosis or regurgitation of the right ventricular outflow tract and pulmonary valve after valved conduit implantation. The findings of autopsy, pathology and laboratory examinations were unremarkable. The implantation of this biosynthetic vascular graft into animals meets the safety and effectiveness requirements for clinical application. This pulmonary arterial conduit has potential clinical application for children with complex congenital heart disease who require pulmonary artery reconstruction to achieve a radical cure. [ABSTRACT FROM AUTHOR]

Background The mechanism underlying left ventricular remodeling and reverse remodeling in the setting of mechanical support following acute myocardial infarction (MI) is unclear. We tested the hypothesis that left ventricular assist device (LVAD) unloading can decrease apoptotic signals after MI. Methods An MI model was created in 16 sheep by coronary artery ligation. Eight were unloaded with a LVAD during the first 2 weeks after MI and observed for 10 more weeks. Myocardial tissue was collected from the nonischemic adjacent zone and the remote zone. Proteins in the apoptotic matrix metalloproteinases (MMPs)-2/c-Jun N-terminal kinase (JNK) and prosurvival β1D-integrin/focal adhesion kinase (FAK) pathway were quantified. Results Increased TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) positive nuclei were observed in the MI group and to a lesser extent in the LVAD group (6.18 ± 0.26 versus 0.82 ± 0.18; p < 0.05). Pro-MMP-2, MMP-2, JNK, and phosphorylated (p)-JNK were all elevated in the adjacent zone of the MI-only group but not in the adjacent zone of the LVAD-supported group. There were higher levels of prosurvival p-FAK in the LVAD-supported group than in the MI group. Conclusions MMP-2/JNK apoptotic and β1D-integrin/FAK survival pathways are activated in the nonischemic adjacent zone after MI in adult sheep. LVAD unloading of approximately 50% cardiac output for 2 weeks attenuates remodeling in part by its negative effect on stretch-induced apoptosis and inhibition of MMP-2 activity. [ABSTRACT FROM AUTHOR]

Respiratory failure is one of the major causes of mortality and morbidity all over the world. Therapeutic options to treat respiratory failure remain limited. The objective of this study was to evaluate the gas transfer performance of a newly developed miniature portable integrated pediatric pump-lung device (PediPL) with small membrane surface for respiratory support in an acute ovine respiratory failure model. The respiratory failure was created in six adult sheep using intravenous anesthesia and reduced mechanical ventilation at 2 breaths/min. The PediPL device was surgically implanted and evaluated for respiratory support in a venovenous configuration between the right atrium and pulmonary artery. The hemodynamics and respiratory status of the animals during support with the device gas transfer performance of the PediPL were studied for 4 h. The animals exhibited respiratory failure 30 min after mechanical ventilation was reduced to 2 breaths/min, indicated by low oxygen partial pressure, low oxygen saturation, and elevated carbon dioxide in arterial blood. The failure was reversed by establishing respiratory support with the PediPL after 30 min. The rates of O2 transfer and CO2 removal of the PediPL were 86.8 and 139.1 mL/min, respectively. The results demonstrated that the PediPL (miniature integrated pump-oxygenator) has the potential to provide respiratory support as a novel treatment for both hypoxia and hypercarbia. The compact size of the PediPL could allow portability and potentially be used in many emergency settings to rescue patients suffering acute lung injury. [ABSTRACT FROM AUTHOR]

Abstract: Background: Large animal models serve as a critical link in the translation of basic science to clinical practice. However, large animal models of myocardial infarction (MI), especially large size MI, have been associated with high mortality because of arrhythmia. The prophylactic effect of amiodarone and lidocaine were retrospectively reviewed in our ovine MI model. Materials and methods: A total of 114 Dorset hybrid sheep with 25%–30% MI were included in the present study. The sheep were prophylactically treated with amiodarone plus lidocaine before ligation of the four to six coronary artery branches supplying the apex of the heart (arrhythmia prevention [AP] group, n = 45) and with epinephrine (shock prevention [SP] group, n = 49), respectively. The sheep without prophylactic treatment (no prevention [NP] group, n = 20) were used as the control group. The incidence of arrhythmia requiring treatment, mortality due to arrhythmia, hemodynamics, and arterial blood gas values during surgery were analyzed in these three groups. Results: No significant difference was found in infarct size among the three groups. The incidence of arrhythmia requiring treatment was significantly decreased in the AP group compared with that in the NP or SP groups (4.4% for AP versus 35% for NP and 45% for SP groups; P < 0.05). The mortality due to lethal arrhythmia was 2.2% in the AP group, significantly lower than that in the NP group (15%) or SP group (18.4%). Other than the heart rate, no significant differences were found in the hemodynamic data between the AP and NP groups. Metabolic acidosis was not observed in any group, as indicated by the pH and lactate values. Conclusions: Prophylactic amiodarone plus lidocaine decreased the mortality due to lethal arrhythmia after acute MI in our sheep model without significant negative effects on the hemodynamics. However, epinephrine improved the hemodynamics but also increased the mortality due to lethal arrhythmia. Thus, prophylactic amiodarone plus lidocaine is recommended to improve the stability in a large MI animal model. [Copyright &y& Elsevier]

BACKGROUND: The infant Jarvik 2000 heart is a very small, hermetically sealed, intracorporeal, axial-flow ventricular assist device (VAD) designed for circulatory support in neonates and infants. The anatomic fit, short-term biocompatibility and hemodynamic performance of the device were evaluated in a neonate piglet model. METHODS: The infant Jarvik 2000 heart with two different blade profiles (low- or high-flow blade design) was tested in 6 piglets (8.8±0.9 kg). Using a median sternotomy, the pump was placed in the left ventricle through the apex without cardiopulmonary bypass. An outflow graft was anastomosed to the ascending aorta. Hemodynamics and biocompatibility were studied for 6 hours. RESULTS: All 6 pumps were implanted without complication. Optimal anatomic positioning was found with the pump body inserted 2.4 cm into the left ventricle. Hemodynamics demonstrated stability throughout the 6-hour duration. The pump flow increased from 0.27 to 0.95 liter/min at increasing speeds from 18 to 31 krpm for the low-flow blade design, whereas the pump flow increased from 0.54 liter/min to 1.12 liters/min at increasing speeds from 16 krpm to 31 krpm for the high-flow blade design. At higher speeds, >80% of flow could be supplied by the device. Blood chemistry and final pathology demonstrated no acute organ injury or thrombosis for either blade design. CONCLUSIONS: The infant Jarvik 2000 heart is anatomically and biologically compatible with an short-term neonate piglet model. This in vivo study demonstrates the future feasibility of this device for clinical use. [ABSTRACT FROM AUTHOR]

Background: To provide long-term ambulatory cardiopulmonary and respiratory support for adult patients, a novel wearable artificial pump-lung device has been developed. The design features and in vitro and acute in vivo performance of this device are reported. Methods: This device features a uniquely designed hollow-fiber membrane bundle integrated with a magnetically levitated impeller that together form one ultracompact pump-lung device, which can be placed like current paracorporeal ventricular assist devices to allow ambulatory support. The device is 117 mm in length and 89 mm in diameter and has a priming volume of 115 ml. In vitro hydrodynamic, gas transfer and biocompatibility experiments were carried out in mock flow-loops using ovine blood. Acute in vivo characterization was conducted in an ovine model by surgically implanting the device between right atrium and pulmonary artery. Results: The in vitro results show that the device with a membrane surface area of 0.8 m2 was capable of pumping blood from 1 to 4 liters/min against a wide range of pressures and transferring oxygen at a rate of up to 180 ml/min at a blood flow of 3.5 liters/min. Standard hemolysis tests demonstrated low hemolysis at the targeted operating condition. The acute in vivo results also confirmed that the device can provide sufficient oxygen transfer with excellent biocompatibility. Conclusions: Based on in vitro and acute in vivo study findings, this highly integrated wearable pump-lung device can provide efficient respiratory support with good biocompatibility and it is ready for long-term evaluation. [Copyright &y& Elsevier]

Water body extraction can help eco-environmental policymakers to intuitively grasp surface water resources. Remote sensing technology can accurately and quickly extract surface water information, which is of great significance for monitoring surface water changes. Fengyun satellite images have the advantages of high time resolution and multispectral bands. This provides important image data suitable for high-frequency surface water monitoring. Based on Fengyun 3 medium resolution spectral imager (FY-3/MERSI) data, 7 methods were applied in this study, which include single-band threshold method, water body index method, knowledge decision tree classification method, supervised classification method, unsupervised classification method, spectral matching based on discrete particle swarm optimization (SMDPSO), and improved spectral matching based on discrete particle swarm optimization with linear feature enhancement (SMDPSO+LFE). These methods were used to extract the land surface water of Poyang Lake, check the samples from the Landsat image with similar times to the FY-3 images, and calculate the classification accuracy via the confusion matrix. The results showed that the overall classification accuracy (OA) of the SMDPSO+LFE is 97.64%, and the Kappa coefficient is 0.95. To analyze the stability of the surface water extracted by SMDPSO+LFE in different regions, this paper selected eight test sites with different surface water types, landscapes, and terrains to extract surface water. Based on an analysis of the land surface water results at the eight test sites, every OA in the eight sites was higher than 94.5%, the Kappa coefficient was greater than 0.88. In conclusion, the SMDPSO+LFE is found to be the most suitable method among the 7 methods and effectively distinguish between different surface water bodies and backgrounds with good stability. [ABSTRACT FROM AUTHOR]

Abstract: Heart transplantation still remains the best choice of treatment for many kinds of end-stage heart diseases, but the side-effects of immunosuppressive agents and cardiac allograft vasculopathy (CAV) remain the main two obstacles in improving the long outcome of cardiac allografts. Mesenchymal stem cells (MSCs) are nonhematopoietic pluripotent cells that retain the ability to undergo differentiation into cells of different lineages. What''s more, MSCs have been demonstrated to exert many profound inhibitory effects on many lymphocytic subpopulations such as T cells, regulatory T cells, and dendritic cells in vitro. In vivo studies also suggested that MSCs could be used to attenuate immune-mediated disorders such as transplant rejection and autoimmune diseases including rheumatoid arthritis, multiple sclerosis and GVHD. Hepatocyte growth factor (HGF) is a pleiotropic factor that plays an important role in protecting infarcted myocardial by its antiapoptotic, antifibrotic and angiogenic effects. And also it was suggested that the administration of HGF could effectively suppress acute and chronic cardiac allograft rejection. We based our hypothesis on that HGF-modified MSCs would engraft stably in recipient and interact with important immune cells such as T cells, B cells and dendritic cells, then stable immune tolerance be induced possibly by both immunomodulation of MSCs and cardioprotective and immunomodulative effects of HGF. Further work is necessary to highlight the specific underlying mechanisms. [Copyright &y& Elsevier]

Abstract: Leptin, a 16kDa peptide product of the obese gene, is an adipocyte-derived cytokine-like molecule which is structurally related to the IL-6 cytokine family. Through its interaction with its receptor Ob-R, a member of the class I cytokine receptor family which is ubiquitously expressed including endothelium, vascular smooth muscle and myocardium, leptin plays a role in a wide range of biological responses such as control of body weight and energy expenditure, neuroendocrine function, angiogenesis, bone formation, modulating immune responses. More and more studies indicated that leptin may be involved in the acute stress response to severe illness and surgery by way of its interaction with hypothalamic–pituitary–adrenal axis and the inflammatory cytokine system. Systemic inflammatory response (SIR) is one of the common complications after on-pump coronary artery bypass grafting in which the severity of SIR directly correlates with the outcome and prognosis. We based our hypothesis on that leptin may participate in the acute stress-SIR induced by on-pump coronary artery bypass grafting and its levels and secretion patterns might be related to the extent of activation of SIR and might serve as marker of the severity and predict the outcome. [Copyright &y& Elsevier]

Abstract: Background: The underlying molecular mechanisms of the remodeling after myocardial infarction (MI) remain unclear. The purpose of this study was to investigate the role of a survival pathway (PI3K/Akt) and an apoptosis pathway (calcineurin/BAD) in the remodeling after MI in a large animal model. Methods: Ten Dorset hybrid sheep underwent 25% MI in the left ventricle (LV, n=10). Five sheep were used as sham control. The regional strain was calculated from sonomicrometry. Apoptosis and the activation of the PI3K/Akt and calcineurin/BAD pathways were evaluated in the non-ischemic adjacent zone and the remote zone relative to infarct by immunoblotting, immunoprecipitation, and immunofluorescence staining. Results: Dilation and dysfunction of LV were present at 12weeks after MI. The regional strain in the adjacent zone was significantly higher than in the remote zone at 12weeks (36.6±4.0% vs 9.5±3.6%, p< 0.05). Apoptosis was more severe in the adjacent zone than in the remote zone. The PI3K/Akt and calcineurin/BAD pathways were activated in the adjacent zone. Dephosphorylation and translocation of BAD were evident in the adjacent zone. Regional correlation between the strain and the expression of calcineurin/BAD indicated that the activation was strain-related (R 2 =0.46, 0.48, 0.39 for calcineurin, BAD, mitochondrial BAD, respectively, p <0.05). Conclusions: The PI3K/Akt survival and calcineurin/BAD apoptotic pathways were concomitantly activated in the non-ischemic adjacent zone after MI. The calcineurin/BAD pathway is strain related and its imbalanced activation may be one of the causes of progressive remodeling after MI. [Copyright &y& Elsevier]

Background: Bovine pericardium can be used for cardiovascular repair surgeries, but challenges involving biocompatibility and durability remain. This study aimed to carry out pre-clinical testing of aortic valve replacement using an aortic valve prosthesis made of bovine pericardium modified with glutaraldehyde (GA) and 2,3-butanediol (BD)., Methods: The mechanical, plasma protein adsorption, platelet adhesion, collagenase digestion, and ninhydrin properties of the material (control vs. GA vs. GA + BD) were tested. All 3 tissues were implanted in rats and observed after 8 weeks under microscopy with alizarin red staining for calcification. Aortic valves made from the fully-treated material were implanted in sheep. A commercial bioprosthesis was used as control. Effectiveness and safety indicators were observed at 180 days after implantation., Results: Compared with the control group, the GA + BD material showed higher elongation at breaking and tensile load (both P<0.05), lower plasma protein adsorption, lower platelet adhesion, lower collagenase digestion, lower ninhydrin value, and higher cross-linking (all P<0.05). After implantation in rat models, the GA + BD material showed little or no dissolution; there was no obvious calcification; and it was surrounded by a small amount of fibrosis, with peripheral capillary proliferation. After implantation in sheep models, the aortic valve leaflets of the experimental animals freely opened and closed, their surface was smooth, and no abnormal echo was observed. The echocardiographic results and hemodynamic were comparable between the two groups. All safety parameters were normal., Conclusions: Modification of bovine pericardium with GA and BD results in a biomaterial with favorable properties for use as an aortic valve prosthesis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-7803). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Objective: To investigate the expression profile of circular RNAs (circRNAs) and proposed circRNA-microRNA (miRNA) regulatory network in atrial fibrillation (AF)., Methods: Atrial tissues from patients with persistent AF with rheumatic heart disease and non-AF myocardium with normal hearts were collected for circRNA differential expression analyses by high-throughput sequencing. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to predict the potential functions of the differentially expressed genes and AF-related pathways. Co-expression networks of circRNA-miRNA were constructed based on the correlation analyses between the differentially expressed RNAs. Quantitative reverse transcription polymerase chain reaction (PCR) was performed to validate the results., Results: A total of 108 circRNAs were found to be differentially expressed in AF. Among them, 51 were up-regulated, and 57 were down-regulated. Dysregulated circRNAs were validated by quantitative real-time PCR. The GO and KEGG pathway enrichment analyses were executed to determine the principal functions of the significantly deregulated genes. Furthermore, we constructed correlated expression networks between circRNAs and miRNAs. circRNA19591, circRNA19596, and circRNA16175 interacted with 36, 28, and 18 miRNAs, respectively; miR-29b-1-5p and miR-29b-2-5p were related to 12 down-regulated circRNAs, respectively., Conclusion: Our findings provide a novel perspective on circRNAs involved in AF due to rheumatic heart disease and establish the foundation for future research of the potential roles of circRNAs in AF.

Despite the significant contribution of the Fontan procedure to the therapy of complex congenital heart diseases, many patients progress to failure of their Fontan circulation. The use of ventricular assist devices to provide circulatory support to these patients remains challenging. In the current study, a continuous axial-flow pump was used to support a univentricular Fontan circulation. A modified Fontan circulation (atrio-pulmonary connection) was constructed in six Yorkshire piglets (8-14 kg). A Dacron conduit (12 mm) with two branches was constructed to serve as a complete atrio-pulmonary connection without the use of cardiopulmonary bypass. The Impella pump was inserted into the conduit through an additional Polytetrafluoroethylene (PTFE) graft in five animals. Hemodynamic data were collected for 6 hours under the supported Fontan circulation. The control animal died after initiating the Fontan circulation independent of resuscitation. Four pump supported animals remained hemodynamically stable for 6 hours with pump speeds between 18,000 rpm and 22,000 rpm (P1-P3). Oxygen saturation was maintained between 95% and 100%. Normal organ perfusion was illustrated by blood gas analysis and biochemical assays. A continuous axial-flow pump can be used for temporal circulatory support to the failing Fontan circulation as "bridge" to heart transplantation or recovery.

Objective: To evaluate the effects of prearrest heparin administration on lung quality in a model of donation after cardiac death (DCD), and to assess the potential application of ex vivo lung perfusion (EVLP) in the identification of better grafts from the DCD donor pool., Methods: Cardiac death was induced by electric shock in 10 pigs. One group received a prearrest heparin dose of 300 units/kg (H group, n = 5) and the other did not (NH group, n = 5). Animals remained at room temperature for 1 hour without ventilation, defining the warm ischemic time. After harvest, the lungs underwent 6 hours of cold ischemia before being evaluated with EVLP for 4 hours., Results: Static compliance 28 ± 3 versus 29 ± 2 (Cstat-cm H2O), pulmonary vascular resistance (PVR) 593 ± 127 versus 495 ± 70 (PVR-dyn·s/cm), and oxygenation 327 ± 32 versus 330 ± 28 (ΔPO2-mm Hg) remained stable from the beginning until the end of EVLP in the H group. In the NH group, Cstat started to decline after the first hour (25 ± 2 vs 21 ± 2), ΔPO2 after hour 2 (265 ± 44 vs 207 ± 44), and PVR started to increase after hour 3 (765 ± 132 vs 916 ± 168). Significant differences between the groups were observed at the end of EVLP (P < 0.001). Parameters of lung quality after EVLP also showed significant differences between the groups: wet weight-to-dry weight ratio (P < 0.001), protein in the bronchial lavage (P < 0.01), Na + K-ATPase activity (P < 0.001), and E-selectin (P < 0.001) in the perfusate., Conclusions: Prearrest heparin administration improved organ function by preserving endothelial homeostasis. EVLP proved to be a useful platform for assessing DCD lungs, providing reliable means of discriminating injured grafts.

There is a scarcity of source material available in animal models appropriate to test pediatric-size blood pump design for assisting the left ventricle. A juvenile ovine animal model was developed to evaluate two pediatric ventricular assist devices (VADs). The child-size Jarvik 2000 and CircuLite VADs were tested with this model. The 33 in vivo experiments were retrospectively studied to evaluate the reliability of the animal model. Dorset hybrid juvenile sheep (20~36 kg) were used to evaluate the small pediatric VADs. Under general anesthesia, a left lateral thoracotomy was performed through the fifth intercostal space. The devices were implanted between the left ventricle apex and the descending aorta without cardiopulmonary bypass. Heparin was infused continuously for anticoagulation therapy. Support duration averaged 26.7 ± 19.6 days. Completion of 75.7% (25/33) experiments was done as intended. The animals were docile and did not require sitters beyond the immediate operative period. Complication includes leg injury, graft infection, gastrointestinal bleeding, intravenous line disconnection, weight loss, renal failure, red urine, (one for each) and pulmonary failure in two. Activated clotting time was adjusted via continuous intravenous heparin to 150-200 seconds. Reliable hemodynamics and biocompatibility data were collected for evaluate pediatric intracorporeal VADs in the animal model. The juvenile sheep model is reliable, reproducible, and translatable for testing pediatric VADs. These experiments provided vital information for improvement of the devices and for clinical application in the future.

Progressive cardiac remodeling, including the myopathic process in the adjacent zone following myocardial infarction (MI), contributes greatly to the development of cardiac failure. Cardiomyoplasty using bone marrow-derived mesenchymal stem cells (MSCs) has been demonstrated to protect cardiomyocytes and/or repair damaged myocardium, leading to improved cardiac performance, but the therapeutic effects on cardiac remodeling are still under investigation. Here, we tested the hypothesis that MSCs could improve the pathological remodeling of the adjacent myocardium abutting the infarct. Allogeneic ovine MSCs were transplanted into the adjacent zone by intracardiac injection 4 hours after infarction. Results showed that remodeling and contractile strain alteration were reduced in the adjacent zone of the MSC-treated group. Cardiomyocyte hypertrophy was significantly attenuated with the normalization of the hypertrophy-related signaling proteins phosphatidylinositol 3-kinase α (PI3Kα), PI3Kγ, extracellular signal-regulated kinase (ERK), and phosphorylated ERK (p-ERK) in the adjacent zone of the MSC-treated group versus the MI-alone group. Moreover, the imbalance of the calcium-handling proteins sarcoplasmic reticulum Ca(2+) adenosine triphosphatase (SERCA2a), phospholamban (PLB), and sodium/calcium exchanger type 1 (NCX-1) induced by MI was prevented by MSC transplantation, and more strikingly, the activity of SERCA2a and uptake of calcium were improved. In addition, the upregulation of the proapoptotic protein Bcl-xL/Bcl-2-associated death promoter (BAD) was normalized, as was phospho-Akt expression; there was less fibrosis, as revealed by staining for collagen; and the apoptosis of cardiomyocytes was significantly inhibited in the adjacent zone by MSC transplantation. Collectively, these data demonstrate that MSC implantation improved the remodeling in the region adjacent to the infarct after cardiac infarction in the ovine infarction model.

Diabetes exacerbates ischemic heart disease morbidity and mortality via incompletely understood mechanisms. Although adiponectin (APN) reduces myocardial ischemia/reperfusion (MI/R) injury in nondiabetic animals, whether APN's cardioprotective actions are altered in diabetes, a pathologic condition with endogenously reduced APN, has never been investigated. High-fat diet (HD)-induced diabetic mice and normal diet (ND) controls were subjected to MI via coronary artery ligation, and given vehicle or APN globular domain (gAPN, 2 μg/g) 10 min before reperfusion. Compared to ND mice (where gAPN exerted pronounced cardioprotection), HD mice manifested greater MI/R injury, and a tripled gAPN dose was requisite to achieve cardioprotective extent seen in ND mice (i.e., infarct size, apoptosis, and cardiac function). APN reduces MI/R injury via AMP-activated protein kinase (AMPK)-dependent metabolic regulation and AMPK-independent antioxidative/antinitrative pathways. Compared to ND, HD mice manifested significantly blunted gAPN-induced AMPK activation, basally and after MI/R (p<0.05). Although both low- and high-dose gAPN equally attenuated MI/R-induced oxidative stress (i.e., NADPH oxidase expression and superoxide production) and nitrative stress (i.e., inducible nitric oxide synthase expression, nitric oxide production, and peroxynitrite formation) in ND mice, only high-dose gAPN efficaciously did so in HD mice. We demonstrate for the first time that HD-induced diabetes diminished both AMPK-dependent and AMPK-independent APN cardioprotection, suggesting an unreported diabetic heart APN resistance.

Objective: Recent clinical observations have indicated that nonlethal mechanical trauma significantly increases myocardial infarction risk even in the presence of completely normal coronary arteries. We investigated the molecular mechanisms responsible for exacerbation of ischemic myocardial injury after nonlethal mechanical trauma with a special focus on the role of tumor necrosis factor α and its potential downstream effector adiponectin, a novel adipokine with anti-inflammatory and cardioprotective properties., Design: Laboratory study., Setting: University research unit., Subjects: Male adult adiponectin knockout mice and wild-type mice., Interventions: The animals were subjected to nonlethal mechanical trauma using the Noble-Collip drum (40 rpm ± 5 mins) followed by myocardial ischemia/reperfusion injury 7 days posttrauma. We also investigated the effects of neutralizing tumor necrosis factor α with etanercept and exogenous adiponectin supplementation on ischemic myocardial injury after trauma., Measurements and Main Results: Trauma significantly sensitized myocardium to ischemia/reperfusion injury as evidenced by increased apoptosis, enlarged infarct size, and decreased cardiac function. Plasma adiponectin concentrations were reduced after traumatic injury (the nadir occurring 3 days posttrauma), an effect abrogated by etanercept-mediated tumor necrosis factor α blockade. The downregulation of adiponectin was accompanied by increased myocardial superoxide and nitric oxide generation and peroxynitrite formation. Both etanercept and exogenous adiponectin supplementation (on day 3 posttrauma or 10 mins before reperfusion on day 7 posttrauma) markedly inhibited oxidative/nitrative stress and ischemia/reperfusion injury in posttraumatic ischemic/reperfused hearts of wild-type mice, whereas only adiponectin supplementation (but not tumor necrosis factor α inhibition) substantially attenuated posttraumatic ischemia/reperfusion injury in adiponectin knockout mice., Conclusions: Tumor necrosis factor α-induced downregulation of adiponectin and the resultant enhanced oxidative/nitrative stress are involved in exacerbated posttraumatic ischemic myocardial injury. Therapeutic approaches blocking tumor necrosis factor α production or restoring adiponectin might have prophylactic value against secondary myocardial ischemic injury after a primary nonlethal mechanical trauma.

Human mitochondrial Mrs2 protein (hsaMrs2p) is a magnesium transporter in mitochondria inner membrane. It was identified as an upregulated gene in a multidrug-resistant (MDR) gastric cancer cell line compared to its parental cells by subtractive hybridization. To further explore the role of hsaMrs2p in MDR of gastric cancer cells, the cDNA encoding hsaMrs2p was generated and mouse antisera against hsaMrs2p was raised with recombinant hsaMrs2p as the immunogen. HsaMrs2p expression could positively regulate adriamycin resistance of SGC7901/ADR cells both in vitro and in vivo. Further study showed that hsaMrs2p increased adriamycin-releasing index. Its upregulation inhibited adriamycin-induced apoptosis, probably by suppressing Bax induced cytochrome C release from mitochondria. Additionally, hsaMrs2p promoted cell growth and cells with decreased hsaMrs2p exhibited significant inhibition of cell growth with G(1) cell cycle arrest. By enhanced hsaMrs2p expression, p27 was downregulated whereas cyclinD1 was upregulated. Our results provide new insights into the function of hsaMrs2p that may be a promising target for MDR reversal therapy.

Objectives: Conventional glutaraldehyde fixation is conducive to calcification of bioprosthetic tissues. The aim of this study was to test calcification resistance of procyanidin-treated decellularized porcine aortic valve in a rat model., Materials and Methods: We performed cross-linking of the decellularized porcine aortic heart valves by procyanidins and observed morphologic performance and examined the tensile strength and cross-linking index. Then we implanted subcutaneous samples of procyanidin cross-linking decellularized valves, glutaraldehyde cross-linking decellularized valves, and decellularized valves in rats. The retrieved grafts were stained with hematoxylin-eosin and von Kossa and were analyzed with scanning electron microscopy and x-ray energy dispersive spectroscopy (EDS) after 21 and 63 days., Results: After decellularized and cross-linking pretreatment, the procyanidin cross-linked leaflets were soft and stretchable. In addition, the cellular components of the porcine aortic heart valve leaflets were completely removed, and the extracelluar matrix was maintained completely. Examination of tensile strength revealed a significantly higher tissue resistance to tension in procyanidin cross-linked tissue than in other tissues, including the glutaraldehyde group (P< .05), even though the extents of cross-linking of each group were roughly the same at approximately 90%. Histopathologic examination showed that the procyanidin cross-linked valve matrix had no significant calcification, and there were no calcium peaks in the EDS profile of procyanidin cross-linked samples in the 21-day and 63-day rat studies., Conclusion: This study demonstrated that procyanidin cross-linked decellularized heart valves can resist calcification to some extent.