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Long-Term Outcome of Combined (Percutaneous Intramyocardial and Intracoronary) Application of Autologous Bone Marrow Mononuclear Cells Post Myocardial Infarction: The 5-Year MYSTAR Study.

Wed, 06/14/2017 - 12:45
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Long-Term Outcome of Combined (Percutaneous Intramyocardial and Intracoronary) Application of Autologous Bone Marrow Mononuclear Cells Post Myocardial Infarction: The 5-Year MYSTAR Study.

PLoS One. 2016;11(10):e0164908

Authors: Gyöngyösi M, Giurgea GA, Syeda B, Charwat S, Marzluf B, Mascherbauer J, Jakab A, Zimba A, Sárközy M, Pavo N, Sochor H, Graf S, Lang I, Maurer G, Bergler-Klein J, MYSTAR investigators

Abstract
OBJECTIVE: The long-term (5-year) outcome of early (3-6 weeks after acute myocardial infarction [AMI], BM-MNC Early group) and late (3-4 months after AMI, BM-MNC Late group) combined (percutaneous intramyocardial and intracoronary) delivery of autologous bone marrow mononuclear cells (BM-MNCs) was evaluated in patients with ejection fractions (EF) between 30-45% post-AMI.
METHODS: Major adverse cardiac and cerebrovascular events (MACCE) and hospitalization were recorded. Left (LV) and right (RV) ventricular function were measured by transthoracic echocardiography. Cardiac magnetic resonance imaging (MRI) and myocardial single photon emission computed tomography was performed in a subgroup of patients. Pre-cell therapy myocardial voltage values of treated areas (assessed by NOGA mapping) were correlated with clinical outcome.
RESULTS: Five-year MACCE incidences (7.4%. vs 24.1%) and the composite of all adverse events (11.1% vs 27.6%) were not different between the Early and Late treatment groups. The significant LV-EF increase at 1-year follow-up was preserved at the 5-year control (from baseline to 5-year: 5.3%, 95% CI:0.5-10.1, and 5.7%, 95% CI:1.7-9.6, p<0.05 in the Early and Late groups, respectively), with no significant changes between 1- and 5-year follow-ups. Similarly, RVEF increased significantly from baseline to the 5-year follow-up (Early group: 5.4%, 95% CI:1.0-9.6; and Late group: 8.4%, 95% CI:4.5-12.3). Lower baseline levels of myocardial viability of the treated cardiac area (6.3±2.4 vs 8.2±3.0 mV, p<0.05) were associated with incidence of MACCE.
CONCLUSIONS: Percutaneous combined delivery of autologous BM-MNCs is feasible and safe after 5 years, and may result in sustained improvement of cardiac function at 5 years in patients with low EF post-AMI (Clinicaltrials.gov NCT01395212).

PMID: 27764157 [PubMed - indexed for MEDLINE]

Constitutive GITR Activation Reduces Atherosclerosis by Promoting Regulatory CD4+ T-Cell Responses-Brief Report.

Wed, 06/14/2017 - 12:45
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Constitutive GITR Activation Reduces Atherosclerosis by Promoting Regulatory CD4+ T-Cell Responses-Brief Report.

Arterioscler Thromb Vasc Biol. 2016 Sep;36(9):1748-52

Authors: Meiler S, Smeets E, Winkels H, Shami A, Pascutti MF, Nolte MA, Beckers L, Weber C, Gerdes N, Lutgens E

Abstract
OBJECTIVE: Glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR) is expressed on CD4(+) effector memory T cells and regulatory T cells; however, its role on these functionally opposing cell types in atherosclerosis is not fully understood.
APPROACH AND RESULTS: Low-density lipoprotein receptor-deficient mice (Ldlr(-/-)) were lethally irradiated and reconstituted with either bone marrow from B-cell-restricted Gitrl transgenic mice or from wild-type controls and fed a high-cholesterol diet for 11 weeks. Chimeric Ldlr(-/-) Gitrl(tg) mice showed a profound increase in both CD4(+) effector memory T cells and regulatory T cells in secondary lymphoid organs. Additionally, the number of regulatory T cells was significantly enhanced in the thymus and aorta of these mice along with increased Gitrl and Il-2 transcript levels. Atherosclerotic lesions of Ldlr(-/-) Gitrl(tg) chimeras contained more total CD3(+) T cells as well as Foxp3(+) regulatory T cells overall, leading to significantly less severe atherosclerosis.
CONCLUSIONS: These data indicate that continuous GITR stimulation through B cell Gitrl acts protective in a mouse model of atherosclerosis by regulating the balance between regulatory and effector memory CD4(+) T cells.

PMID: 27444204 [PubMed - indexed for MEDLINE]

Validation of microbiological testing in cardiovascular tissue banks: results of a quality round trial.

Tue, 06/13/2017 - 12:45

Validation of microbiological testing in cardiovascular tissue banks: results of a quality round trial.

Eur J Cardiothorac Surg. 2017 Jun 12;:

Authors: de By TMMH, McDonald C, Süßner S, Davies J, Heng WL, Jashari R, Bogers AJJC, Petit P

Abstract
OBJECTIVES: Surgeons needing human cardiovascular tissue for implantation in their patients are confronted with cardiovascular tissue banks that use different methods to identify and decontaminate micro-organisms. To elucidate these differences, we compared the quality of processing methods in 20 tissue banks and 1 reference laboratory. We did this to validate the results for accepting or rejecting tissue. We included the decontamination methods used and the influence of antibiotic cocktails and residues with results and controls. The minor details of the processes were not included.
METHODS: To compare the outcomes of microbiological testing and decontamination methods of heart valve allografts in cardiovascular tissue banks, an international quality round was organized. Twenty cardiovascular tissue banks participated in this quality round. The quality round method was validated first and consisted of sending purposely contaminated human heart valve tissue samples with known micro-organisms to the participants. The participants identified the micro-organisms using their local decontamination methods.
RESULTS: Seventeen of the 20 participants correctly identified the micro-organisms; if these samples were heart valves to be released for implantation, 3 of the 20 participants would have decided to accept their result for release. Decontamination was shown not to be effective in 13 tissue banks because of growth of the organisms after decontamination. Articles in the literature revealed that antibiotics are effective at 36°C and not, or less so, at 2-8°C. The decontamination procedure, if it is validated, will ensure that the tissue contains no known micro-organisms.
CONCLUSIONS: This study demonstrates that the quality round method of sending contaminated tissues and assessing the results of the microbiological cultures is an effective way of validating the processes of tissue banks. Only when harmonization, based on validated methods, has been achieved, will surgeons be able to fully rely on the methods used and have confidence in the consistent sterility of the tissue grafts. Tissue banks should validate their methods so that all stakeholders can trust the outcomes.

PMID: 28605496 [PubMed - as supplied by publisher]

Prognostic value of mean pulmonary artery pressure in the stable phase after heart transplantation.

Tue, 06/13/2017 - 12:45

Prognostic value of mean pulmonary artery pressure in the stable phase after heart transplantation.

Eur J Cardiothorac Surg. 2017 Jun 09;:

Authors: Molkentin JP, Nägele MP, Frank M, Sudano I, Enseleit F, Wilhelm MJ, Lüscher TF, Maisano F, Ruschitzka F, Flammer AJ

Abstract
OBJECTIVES: In heart transplant recipients, elevated mean pulmonary artery pressure (mPAP) shortly before or after transplantation represents a powerful predictor for an adverse short-term outcome. Less is known on cardiac and pulmonary pressures measured in the stable phase after heart transplantation. The aim of this study was to assess the predictive value of mPAP, mean pulmonary capillary wedge pressure and mean central venous pressure in the stable phase after transplantation.
METHODS: All patients ( n  = 260, mean age 47.4 ± 12.7 years, 224 males) who received a cardiac allograft at the University Hospital Zurich between September 1985 and August 2014 and who had undergone at least 1 right heart catheterization after transplantation (median 358 days after transplantation) were included and survival analysis was performed (median follow-up 11.9 years).
RESULTS: The median mPAP, mean pulmonary capillary wedge pressure and mean central venous pressure were 15 mmHg (interquartile range 12-19 mmHg), 8 mmHg (interquartile range 6-11 mmHg) and 3 mmHg (interquartile range 1-5 mmHg), respectively. In mPAP median split survival analysis, patients with an mPAP above the median had a significantly lower long-term survival than patients with or below median mPAP ( P  = 0.012). mPAP but not mean central venous pressure or mean pulmonary capillary wedge pressure was independently associated with long-term mortality in multivariable Cox-hazard survival analysis (hazard ratio 1.10, confidence interval 1.04-1.16, P  = 0.001). Other factors independently associated with mortality were age at transplantation (hazard ratio 1.03 per year, confidence interval 1.01-1.04, P  = 0.002) and serum creatinine (μmol/l) (hazard ratio 1.003, confidence interval 1.001-1.010, P  = 0.021).
CONCLUSIONS: Our results demonstrate that mPAP measured in the stable phase after heart transplantation is an independent prognostic factor for long-term mortality.

PMID: 28605420 [PubMed - as supplied by publisher]

Cellular Therapies for Treatment of Radiation Injury: Report from a NIH/NIAID and IRSN Workshop.

Tue, 06/13/2017 - 12:45

Cellular Therapies for Treatment of Radiation Injury: Report from a NIH/NIAID and IRSN Workshop.

Radiat Res. 2017 Jun 12;:

Authors: DiCarlo AL, Tamarat R, Rios CI, Benderitter M, Czarniecki CW, Allio TC, Macchiarini F, Maidment BW, Jourdain JR

Abstract
In recent years, there has been increasing concern over the possibility of a radiological or nuclear incident occurring somewhere in the world. Intelligence agencies frequently report that terrorist groups and rogue nations are seeking to obtain radiological or nuclear weapons of mass destruction. In addition, there exists the real possibility that safety of nuclear power reactors could be compromised by natural (such as the tsunami and subsequent Fukushima accident in Japan in March, 2011) or accidental (Three Mile Island, 1979 and Chernobyl, 1986) events. Although progress has been made by governments around the world to prepare for these events, including the stockpiling of radiation countermeasures, there are still challenges concerning care of patients injured during a radiation incident. Because the deleterious and pathological effects of radiation are so broad, it is desirable to identify medical countermeasures that can have a beneficial impact on several tissues and organ systems. Cellular therapies have the potential to impact recovery and tissue/organ regeneration for both early and late complications of radiation exposure. These therapies, which could include stem or blood progenitor cells, mesenchymal stromal cells (MSCs) or cells derived from other tissues (e.g., endothelium or placenta), have shown great promise in treating other nonradiation injuries to and diseases of the bone marrow, skin, gastrointestinal tract, brain, lung and heart. To explore the potential use of these therapies in the treatment of victims after acute radiation exposure, the National Institute of Allergy and Infectious Diseases co-sponsored an international workshop in July, 2015 in Paris, France with the Institut de Radioprotection et de Sûreté Nucléaire. The workshop included discussions of data available from testing in preclinical models of radiation injury to different organs, logistics associated with the practical use of cellular therapies for a mass casualty incident, as well as international regulatory requirements for authorizing such drug products to be legally and readily used in such incidents. This report reviews the data presented, as well as key discussion points from the meeting.

PMID: 28605260 [PubMed - as supplied by publisher]

Recent Progress Using Pluripotent Stem Cells for Cardiac Regenerative Therapy.

Tue, 06/13/2017 - 12:45
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Recent Progress Using Pluripotent Stem Cells for Cardiac Regenerative Therapy.

Circ J. 2017 Jun 10;:

Authors: Ichimura H, Shiba Y

Abstract
Pluripotent stem cells (PSCs) have gained interest for cell-based regenerative therapies because of their capacity to differentiate into most somatic cell types, including cardiomyocytes. Remarkable progress in the generation of PSC-derived cardiomyocytes has been made in this decade, and recent preclinical transplantation studies using various animal models have provided proof-of-principle for their use in heart regeneration. However, several obstacles preclude their effective and safe clinical application for cardiac repair, including the need for approaches that prevent tumorigenesis, arrhythmogenesis, and immune rejection. In this review, we focus on recent progress in the field of PSC-based cardiac regenerative therapy, including the remaining hurdles and potential approaches to circumventing them.

PMID: 28603177 [PubMed - as supplied by publisher]

Association of Pre-Procedural Cardiac Magnetic Resonance Imaging with Outcomes of Ventricular Tachycardia Ablation in Patients with Idiopathic Dilated Cardiomyopathy.

Tue, 06/13/2017 - 12:45
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Association of Pre-Procedural Cardiac Magnetic Resonance Imaging with Outcomes of Ventricular Tachycardia Ablation in Patients with Idiopathic Dilated Cardiomyopathy.

Heart Rhythm. 2017 Jun 08;:

Authors: Siontis KC, Kim HM, Dabbagh GS, Latchamsetty R, Stojanovska J, Jongnarangsin K, Morady F, Bogun FM

Abstract
BACKGROUND: Knowledge of complex arrhythmogenic substrates can help plan ventricular tachycardia (VT) ablation in idiopathic dilated cardiomyopathy (DCM).
OBJECTIVE: We sought to assess whether pre-procedural late-gadolinium enhancement magnetic resonance imaging (LGE-MRI) can improve ablation outcomes in DCM.
METHODS: Consecutive patients (n=96) with idiopathic DCM underwent VT ablation with open-irrigated catheters (2006-2016). Before 2012, LGE-MRI was not performed at our institution in patients with implanted devices, but it has been performed routinely in all patients after the implementation of a new MRI protocol in 2012. We retrospectively compared acute and long-term outcomes of initial VT ablation procedures in patients with (n=41) and without (n=55) pre-procedural LGE-MRI. Procedural outcome was classified as successful if VT was not inducible post-ablation.
RESULTS: The 2 groups had a similar mean age and ejection fraction, comorbidities, and frequency of epicardial ablation. Pre-ablation LGE-MRI was independently associated with improved procedural success (63% vs 24%) by logistic regression analysis (adjusted odds ratio [OR]=7.86, p<0.001). This result was consistent even when patients with non-diagnostic MRIs due to artifact were included in the imaging group (OR=4.87, p=0.005). Pre-ablation imaging was also associated with improved survival free of the composite endpoint of VT recurrence, heart transplantation, or death, which was met by 11 (27%) and 33 (60%) patients in the imaging and "no imaging" groups, respectively, after median 7.6 months of follow-up (unadjusted log-rank p=0.02). However, there was no association with long-term outcomes after adjustment for other covariates.
CONCLUSION: Pre-procedural imaging with LGE-MRI may be associated with improved outcomes of VT ablation in DCM.

PMID: 28603002 [PubMed - as supplied by publisher]

Granulocyte colony-stimulating factor for the treatment of cardiovascular diseases: an update with a critical appraisal.

Tue, 06/13/2017 - 12:45
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Granulocyte colony-stimulating factor for the treatment of cardiovascular diseases: an update with a critical appraisal.

Pharmacol Res. 2017 Jun 07;:

Authors: D'Amario D, Leone AM, Borovac JA, Cannata F, Siracusano A, Niccoli G, Crea F

Abstract
Heart failure and acute myocardial infarction are conditions that are associated with high morbidity and mortality. Significant dysfunction of the heart muscle can occur as the consequence of end-stage chronic cardiovascular diseases or acute ischemic events that are marked by large infarction area and significant tissue necrosis. Despite the remarkable improvement of conventional treatments, a substantial proportion of patients still develops severe heart failure that can only be resolved by heart transplantation or mechanical device implantation. Therefore, novel approaches based on stem-cell therapy can directly modify the disease process and alter its prognosis. The ability of the stem-cells to modify and repair the injured myocardium is a challenging but intriguing concept that can potentially replace expensive and invasive methods of treatment that are associated with increased risks and significant financial costs. In that sense, granulocyte colony-stimulating factor (G-CSF) seems as an attractive treatment approach. Based on the series of pre-clinical experiments and a limited amount of clinical data, it was demonstrated that G-CSF agents possess the ability to mobilize stem-cells from bone marrow and induce their differentiation into cardiomyocytes or endothelial cells when brought into contact with injured regions of the myocardium. However, clinical benefits of G-CSF use in damaged myocardium remain unclear and are the topic of expert discussion. The main goal of this review is to present relevant and up-to-date evidence on G-CSF therapy use in pre-clinical models and in humans and to provide a rationale for its potential clinical applications in the future.

PMID: 28602846 [PubMed - as supplied by publisher]

Left Ventricular Assist Device in Older Adults.

Tue, 06/13/2017 - 12:45
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Left Ventricular Assist Device in Older Adults.

Heart Fail Clin. 2017 Jul;13(3):619-632

Authors: Caraang C, Lanier GM, Gass A, Aronow WS, Gupta CA

Abstract
Left ventricular assist devices (LVADs) are an effective therapy for a growing and aging population in the background of limited donor supply. Selecting the proper patient involves assessment of indications, risk factors, scores for overall outcomes, assessment for right ventricular failure, and optimal timing of implantation. LVAD complications have a 5% to 10% perioperative mortality and complications of bleeding, thrombosis, stroke, infection, right ventricular failure, and device failure. As LVAD engineering technology evolves, so will the risk-prediction scores. Hence, more large-scale prospective data from multicenters will continually be required to aid in patient selection, reduce complications, and improve long-term outcomes.

PMID: 28602376 [PubMed - in process]

Renal Allograft Outcome After Simultaneous Heart and Kidney Transplantation.

Tue, 06/13/2017 - 12:45
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Renal Allograft Outcome After Simultaneous Heart and Kidney Transplantation.

Am J Cardiol. 2017 May 11;:

Authors: Grupper A, Grupper A, Daly RC, Pereira NL, Hathcock MA, Kremers WK, Cosio FG, Edwards BS, Kushwaha SS

Abstract
Chronic kidney disease frequently accompanies end-stage heart failure and may result in consideration of simultaneous heart and kidney transplantation (SHKT). In recent years, there has been a significant increase in SHKT. This single-center cohort consisted of 35 patients who underwent SHKT during 1996 to 2015. The aim of this study was to review factors that may predict better long-term outcome after SKHT. Thirteen patients (37%) had delayed graft function (DGF) after transplant (defined as the need for dialysis during the first 7 days after transplant), which was significantly associated with mechanical circulatory support device therapy and high right ventricular systolic pressure before transplant. Most of the recipients had glomerular filtration rate (GFR) ≥50 ml/min/1.73 m(2) at 1 and 3 years after transplant (21 of 26 [81%] and 20 of 21 [95%], respectively). Higher donor age was associated with reduced 1-year GFR (p = 0.017), and higher recipient pretransplant body mass index was associated with reduced 3-year GFR (p = 0.008). There was a significant association between DGF and reduced median GFR at 1 and 3 years after transplant (p <0.005). Patient survival rates at 6 months, 1, and 3 years after transplant were 97%, 91%, and 86% respectively. In conclusions, our data support good outcomes after SHKT. Mechanical circulatory support device therapy and pulmonary hypertension before transplant are associated with DGF, which is a risk factor for poor long-term renal allograft function.

PMID: 28602210 [PubMed - as supplied by publisher]

Increased Proangiogenic Activity of Mobilized CD34+ Progenitor Cells of Patients With Acute ST-Segment-Elevation Myocardial Infarction: Role of Differential MicroRNA-378 Expression.

Tue, 06/13/2017 - 12:45
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Increased Proangiogenic Activity of Mobilized CD34+ Progenitor Cells of Patients With Acute ST-Segment-Elevation Myocardial Infarction: Role of Differential MicroRNA-378 Expression.

Arterioscler Thromb Vasc Biol. 2017 Feb;37(2):341-349

Authors: Templin C, Volkmann J, Emmert MY, Mocharla P, Müller M, Kraenkel N, Ghadri JR, Meyer M, Styp-Rekowska B, Briand S, Klingenberg R, Jaguszewski M, Matter CM, Djonov V, Mach F, Windecker S, Hoerstrup SP, Thum T, Lüscher TF, Landmesser U

Abstract
OBJECTIVE: Proangiogenic effects of mobilized bone marrow-derived stem/progenitor cells are essential for cardiac repair after myocardial infarction. MicroRNAs (miRNA/miR) are key regulators of angiogenesis. We investigated the differential regulation of angio-miRs, that is, miRNAs regulating neovascularization, in mobilized CD34(+) progenitor cells obtained from patients with an acute ST-segment-elevation myocardial infarction (STEMI) as compared with those with stable coronary artery disease or healthy subjects.
APPROACH AND RESULTS: CD34(+) progenitor cells were isolated from patients with STEMI (on day 0 and day 5), stable coronary artery disease, and healthy subjects (n=27). CD34(+) progenitor cells of patients with STEMI exhibited increased proangiogenic activity as compared with CD34(+) cells from the other groups. Using a polymerase chain reaction-based miRNA-array and real-time polymerase chain reaction validation, we identified a profound upregulation of 2 known angio-miRs, that are, miR-378 and let-7b, in CD34(+) cells of patients with STEMI. Especially, we demonstrate that miR-378 is a critical regulator of the proangiogenic capacity of CD34(+) progenitor cells and its stimulatory effects on endothelial cells in vitro and in vivo, whereas let-7b upregulation in CD34(+) cells failed to proof its effect on endothelial cells in vivo.
CONCLUSIONS: The present study demonstrates a significant upregulation of the angio-miRs miR-378 and let-7b in mobilized CD34(+) progenitor cells of patients with STEMI. The increased proangiogenic activity of these cells in patients with STEMI and the observation that in particular miR-378 regulates the angiogenic capacity of CD34(+) progenitor cells in vivo suggest that this unique miRNA expression pattern represents a novel endogenous repair mechanism activated in acute myocardial infarction.

PMID: 28062497 [PubMed - indexed for MEDLINE]

Mesenchymal stromal cell therapy in ischemic heart disease.

Tue, 06/13/2017 - 12:45
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Mesenchymal stromal cell therapy in ischemic heart disease.

Scand Cardiovasc J. 2016 Oct - Dec;50(5-6):293-299

Authors: Kastrup J, Mygind ND, Qayyum AA, Mathiasen AB, Haack-Sørensen M, Ekblond A

Abstract
Although, treatment of ischemic heart disease (IHD) has improved considerably within the last decades, it is still the main cause of death worldwide. Despite maximum treatment, many IHD patients suffer from refractory angina and heart failure, which severely limits their daily lives. Moreover, IHD is very costly for the health care system. Therefore, new treatment options and strategies are being researched intensely. Stem cell therapy to improve myocardial perfusion and stimulate growth of new cardiomyocytes could be a new way to go. Nevertheless, the results from clinical studies have varied considerably, probably due to the use of many different cell lines obtained from different tissues and the different patient populations. The present review will focus on treatment with the mesenchymal stromal cell from bone marrow and adipose tissue in animal and patients with acute and chronic IHD (CIHD).

PMID: 27380735 [PubMed - indexed for MEDLINE]

The cytoprotective capacity of processed human cardiac extracellular matrix.

Tue, 06/13/2017 - 12:45
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The cytoprotective capacity of processed human cardiac extracellular matrix.

J Mater Sci Mater Med. 2016 Jul;27(7):120

Authors: Kappler B, Anic P, Becker M, Bader A, Klose K, Klein O, Oberwallner B, Choi YH, Falk V, Stamm C

Abstract
Freshly isolated human cardiac extracellular matrix sheets (cECM) have been shown to support stem cell proliferation and tissue-specific lineage commitment. We now developed a protocol for standardized production of durable, bio-functional hcECM microparticles and corresponding hydrogel, and tested its cytoprotective effects on contractile cells subjected to ischemia-like conditions. Human ventricular myocardium was decellularized by a 3-step protocol, including Tris/EDTA, SDS and serum incubation (cECM). Following snap-freezing and lyophilization, microparticles were created and characterized by laser diffraction, dynamic image analysis (DIA), and mass spectrometry. Moreover, cECM hydrogel was produced by pepsin digestion. Baseline cell-support characteristics were determined using murine HL-1 cardiomyocytes, and the cytoprotective effects of ECM products were tested under hypoxia and glucose/serum deprivation. In cECM, glycoproteins (thrombospondin 1, fibronectin, collagens and nidogen-1) and proteoglycans (dermatopontin, lumican and mimecan) were preserved, but residual intracellular and blood-borne proteins were also detected. The median particle feret diameter was 66 μm (15-157 μm) by laser diffraction, and 57 μm (20-182 μm) by DIA with crystal violet staining. HL-1 cells displayed enhanced metabolic activity (39 ± 12 %, P < 0.05) and proliferation (16 ± 3 %, P < 0.05) when grown on cECM microparticles in normoxia. During simulated ischemia, cECM microparticles exerted distinct cytoprotective effects (MTS conversion, 240 ± 32 %; BrdU uptake, 45 ± 14 %; LDH release, -72 ± 7 %; P < 0.01, each). When cECM microparticles were solubilized to form a hydrogel, the cytoprotective effect was initially abolished. However, modifying the preparation process (pepsin digestion at pH 2 and 25 °C, 1 mg/ml final cECM concentration) restored the cytoprotective cECM activity. Extracellular matrix from human myocardium can be processed to yield standardized durable microparticles that exert specific cytoprotective effects on cardiomyocyte-like cells. The use of processed cECM may help to optimize future clinical-grade myocardial tissue engineering approaches.

PMID: 27272902 [PubMed - indexed for MEDLINE]

Myocardial Response to Milrinone in Single Right Ventricle Heart Disease.

Tue, 06/13/2017 - 12:45
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Myocardial Response to Milrinone in Single Right Ventricle Heart Disease.

J Pediatr. 2016 Jul;174:199-203.e5

Authors: Nakano SJ, Nelson P, Sucharov CC, Miyamoto SD

Abstract
OBJECTIVES: Empiric treatment with milrinone, a phosphodiesterase (PDE) 3 inhibitor, has become increasingly common in patients with single ventricle heart disease of right ventricular (RV) morphology (SRV); our objective was to characterize the myocardial response to PDE3 inhibition (PDE3i) in the pediatric population with SRV.
STUDY DESIGN: Cyclic adenosine monophosphate levels, PDE activity, and phosphorylated phospholamban (PLN) were determined in explanted human ventricular myocardium from nonfailing pediatric donors (n = 10) and pediatric patients transplanted secondary to SRV. Subjects with SRV were further classified by PDE3i treatment (n = 13 with PDE3i and n = 12 without PDE3i).
RESULTS: In comparison with nonfailing RV myocardium (n = 8), cyclic adenosine monophosphate levels are lower in patients with SRV treated with PDE3i (n = 12, P = .021). Chronic PDE3i does not alter total PDE or PDE3 activity in SRV myocardium. Compared with nonfailing RV myocardium, SRV myocardium (both with and without PDE3i) demonstrates equivalent phosphorylated PLN at the protein kinase A phosphorylation site.
CONCLUSIONS: As evidenced by preserved phosphorylated PLN, the molecular adaptation associated with SRV differs significantly from that demonstrated in pediatric heart failure because of dilated cardiomyopathy. These alterations support a pathophysiologically distinct mechanism of heart failure in pediatric patients with SRV, which has direct implications regarding the presumed response to PDE3i treatment in this population.

PMID: 27181939 [PubMed - indexed for MEDLINE]

Closed-loop regulation of arterial pressure after acute brain death.

Mon, 06/12/2017 - 12:45
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Closed-loop regulation of arterial pressure after acute brain death.

J Clin Monit Comput. 2017 Jun 10;:

Authors: Soltesz K, Sjöberg T, Jansson T, Johansson R, Robertsson A, Paskevicius A, Liao Q, Qin G, Steen S

Abstract
The purpose of this concept study was to investigate the possibility of automatic mean arterial pressure (MAP) regulation in a porcine heart-beating brain death (BD) model. Hemodynamic stability of BD donors is necessary for maintaining acceptable quality of donated organs for transplantation. Manual stabilization is challenging, due to the lack of vasomotor function in BD donors. Closed-loop stabilization therefore has the potential of increasing availability of acceptable donor organs, and serves to indicate feasibility within less demanding patient groups. A dynamic model of nitroglycerine pharmacology, suitable for controller synthesis, was identified from an experiment involving an anesthetized pig, using a gradient-based output error method. The model was used to synthesize a robust PID controller for hypertension prevention, evaluated in a second experiment, on a second, brain dead, pig. Hypotension was simultaneously prevented using closed-loop controlled infusion of noradrenaline, by means of a previously published controller. A linear model of low order, with variable (uncertain) gain, was sufficient to describe the dynamics to be controlled. The robustly tuned PID controller utilized in the second experiment kept the MAP within a user-defined range. The system was able to prevent hypertension, exceeding a reference of 100 mmHg by more than 10%, during 98% of a 12 h experiment. This early work demonstrates feasibility of the investigated modelling and control synthesis approach, for the purpose of maintaining normotension in a porcine BD model. There remains a need to characterize individual variability, in order to ensure robust performance over the expected population.

PMID: 28602010 [PubMed - as supplied by publisher]

Empagliflozin in the management of diabetes mellitus after cardiac transplantationResearch Correspondenceretain-->.

Mon, 06/12/2017 - 12:45
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Empagliflozin in the management of diabetes mellitus after cardiac transplantationResearch Correspondenceretain-->.

J Heart Lung Transplant. 2017 May 04;:

Authors: Muir CA, Greenfield JR, MacDonald PS

PMID: 28601371 [PubMed - as supplied by publisher]

Intracellular complement - the complosome - in immune cell regulation.

Mon, 06/12/2017 - 12:45
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Intracellular complement - the complosome - in immune cell regulation.

Mol Immunol. 2017 Jun 07;:

Authors: Arbore G, Kemper C, Kolev M

Abstract
The complement system was defined over a century ago based on its ability to "complement" the antibody-mediated and cell-mediated immune responses against pathogens. Today our understanding of this ancient part of innate immunity has changed substantially and we know now that complement plays an undisputed pivotal role in the regulation of both innate and adaptive immunity. The complement system consists of over 50 blood-circulating, cell-surface expressed and intracellular proteins. It is key in the recognition and elimination of invading pathogens, also in the removal of self-derived danger such as apoptotic cells, and it supports innate immune responses and the initiation of the general inflammatory reactions. The long prevailing classic view of complement was that of a serum-operative danger sensor and first line of defence system, however, recent experimental and clinical evidences have demonstrated that "local" tissue and surprisingly intracellular complement (the complosome) activation impacts on normal cell physiology. This review will focus on novel aspects of intracellular complement activation and its unexpected roles in basic cell processes such as metabolism. We also discuss what the existence of the complosome potentially means for how the host handles intracellular pathogens such as viruses.

PMID: 28601357 [PubMed - as supplied by publisher]

Minimally invasive posterior basilar segmentectomy by a posterior approach: Should we start flipping?

Sun, 06/11/2017 - 10:03
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Minimally invasive posterior basilar segmentectomy by a posterior approach: Should we start flipping?

J Thorac Cardiovasc Surg. 2017 May 17;:

Authors: Podgaetz E, Schwartz GS, Mason DP

PMID: 28599974 [PubMed - as supplied by publisher]

ESRD After Heart Failure, Myocardial Infarction, or Stroke in Type 2 Diabetic Patients With CKD.

Sun, 06/11/2017 - 10:03
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ESRD After Heart Failure, Myocardial Infarction, or Stroke in Type 2 Diabetic Patients With CKD.

Am J Kidney Dis. 2017 Jun 06;:

Authors: Charytan DM, Solomon SD, Ivanovich P, Remuzzi G, Cooper ME, McGill JB, Parving HH, Parfrey P, Singh AK, Burdmann EA, Levey AS, de Zeeuw D, Eckardt KU, McMurray JJV, Claggett B, Lewis EF, Pfeffer MA

Abstract
BACKGROUND: How cardiovascular (CV) events affect progression to end-stage renal disease (ESRD), particularly in the setting of type 2 diabetes, remains uncertain.
STUDY DESIGN: Observational study.
SETTING & PARTICIPANTS: 4,022 patients with type 2 diabetes, anemia, and chronic kidney disease from the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT).
PREDICTOR: Postrandomization CV events.
OUTCOMES: ESRD (defined as initiation of dialysis for >30 days, kidney transplantation, or refusal or nonavailability of renal replacement therapy) and post-ESRD mortality within 30 days and during overall follow-up after an intercurrent CV event.
LIMITATIONS: Population limited to clinical trial participants with diabetes and anemia.
RESULTS: 155 of 652 (23.8%) ESRD cases occurred after an intercurrent CV event; 110 (16.9%) cases followed heart failure, 28 (4.3%) followed myocardial infarction, 12 (1.84%) followed stroke, and 5 (0.77%) followed multiple CV events. ESRD rate was higher within 30 days in individuals with an intercurrent CV event compared with those without an intercurrent event (HR, 22.2; 95% CI, 17.0-29.0). Compared to no intercurrent CV events, relative risks for ESRD were higher after the occurrence of heart failure overall (HR, 3.4; 95% CI, 2.7-4.2) and at 30 days (HR, 20.1; 95% CI, 14.5-27.9) than after myocardial infarction or stroke (P<0.001). Compared with individuals without pre-ESRD events, those with ESRD following intercurrent CV events were older, were more likely to have prior CV disease, and had higher (24.4 vs 23.1mL/min/1.73m(2); P=0.01) baseline estimated glomerular filtration rates (eGFRs) and higher eGFRs at last measurement before ESRD (18.6 vs 15.2mL/min/1.73m(2); P<0.001), whereas race, sex, and medication use were similar. Post-ESRD mortality was similar (P=0.3) with and without preceding CV events.
CONCLUSIONS: Most ESRD cases occurred in individuals without intercurrent CV events who had lower eGFRs than individuals with intercurrent CV events, but similar post-ESRD mortality. Nevertheless, intercurrent CV events, particularly heart failure, are strongly associated with risk for ESRD. These findings underscore the need for kidney-specific therapies in addition to treatment of CV risk factors to lower ESRD incidence in diabetes.

PMID: 28599901 [PubMed - as supplied by publisher]

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