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Extracorporeal Membrane Oxygenation: An Expanding Role in Cardiovascular Care.

Tue, 12/05/2017 - 13:45

Extracorporeal Membrane Oxygenation: An Expanding Role in Cardiovascular Care.

Heart Lung Circ. 2018 Jan;27(1):3-5

Authors: Buscher H, Hayward C

PMID: 29198832 [PubMed - in process]

Circadian Clock-Mediated Regulation of Blood Pressure.

Tue, 12/05/2017 - 13:45

Circadian Clock-Mediated Regulation of Blood Pressure.

Free Radic Biol Med. 2017 Nov 30;:

Authors: Douma LG, Gumz ML

Abstract
Most bodily functions vary over the course of a 24 hour day. Circadian rhythms in body temperature, sleep-wake cycles, metabolism, and blood pressure (BP) are just a few examples. These circadian rhythms are controlled by the central clock in the suprachiasmatic nucleus (SCN) of the hypothalamus and peripheral clocks located throughout the body. Light and food cues entrain these clocks to the time of day and this synchronicity contributes to the regulation of a variety of physiological processes with effects on overall health. The kidney, brain, nervous system, vasculature, and heart have been identified through the use of mouse models and clinical trials as peripheral clock regulators of BP. The dysregulation of this circadian pattern of BP, with or without hypertension, is associated with increased risk for cardiovascular disease. The mechanism of this dysregulation is unknown and is a growing area of research. In this review, we highlight research of human and mouse circadian models that has provided insight into the roles of these molecular clocks and their effects on physiological functions. Additional tissue-specific studies of the molecular clock mechanism are needed, as well as clinical studies including more diverse populations (different races, female patients, etc.), which will be critical to fully understand the mechanism of circadian regulation of BP. Understanding how these molecular clocks regulate the circadian rhythm of BP is critical in the treatment of circadian BP dysregulation and hypertension.

PMID: 29198725 [PubMed - as supplied by publisher]

Reversible Cerebral Vasoconstriction Syndrome After Heart Transplantation: A Case Report.

Tue, 12/05/2017 - 13:45

Reversible Cerebral Vasoconstriction Syndrome After Heart Transplantation: A Case Report.

Transplant Proc. 2017 Dec;49(10):2415-2418

Authors: Kumai Y, Seguchi O, Sato T, Wada K, Shiozawa M, Yokota C, Kuroda K, Nakajima S, Sato T, Yanase M, Matsumoto Y, Fukushima S, Fujita T, Kobayashi J, Fukushima N

Abstract
BACKGROUND: Reversible cerebral vasoconstriction syndrome (RCVS) is a transient cerebrovascular disorder putatively caused by some immunosuppressive agents.
CASE REPORT: We recently encountered a 47-year-old female patient diagnosed with dilated cardiomyopathy who developed RCVS after heart transplantation. A triple-drug regimen consisting of tacrolimus, mycophenolate mofetil, and a corticosteroid was started after surgery. On postoperative day (POD) 11, the patient developed a severe headache, although computed tomography of the head demonstrated no signs of hemorrhage or infarction. At first, both a painkiller and migraine drugs were regularly administered to the patient. On POD 21, however, she developed an unbearable headache with a visual field defect and mild hemiparesis of the right hand. Magnetic resonance imaging (MRI) of the brain revealed a cerebral infarction in the left occipital lobe with diffuse vasoconstriction of both the middle and posterior cerebral arteries. A diagnosis of RCVS was made and tacrolimus, a drug suspected to cause RCVS, was discontinued. In its place, two doses of basiliximab followed by everolimus, both of which are alternatives for tacrolimus, were given. The corticosteroid dose was also increased. Furthermore, to release vasoconstriction, both verapamil and diltiazem were administered. On POD 27, cerebrovascular constrictions were shown to be relieved on brain MRI and the patient's neurological symptoms subsequently almost completely diminished.
CONCLUSION: RCVS should always be considered as a cause of headache in heart transplant recipients because tacrolimus, an immunosuppressive agent, may trigger RCVS. This will allow rapid intervention that is essential for avoiding irreversible neurological deficits.

PMID: 29198694 [PubMed - in process]

Successful Liver Transplantation From a Donor With a Continuous-Flow Left Ventricular Assist Device for 9 Months.

Tue, 12/05/2017 - 13:45

Successful Liver Transplantation From a Donor With a Continuous-Flow Left Ventricular Assist Device for 9 Months.

Transplant Proc. 2017 Dec;49(10):2406-2408

Authors: Munawar K, Rajagopalan N, Grigorian A, Dennis D, Guglin M

Abstract
Organ donor criteria continue to be extended in an attempt to meet growing demands. Patients with continuous-flow left ventricular assist devices are one group of potential donors being considered. One concern with this group is the effect of continuous flow for a prolonged duration, as opposed to normal pulsatile flow, on end-organ function. We report the 1st case of a liver transplantation from a donor who had a continuous-flow left ventricular assist device for 9 months. The recipient was a 69-year-old woman with a history of cryptogenic cirrhosis and hepatocellular carcinoma. The transplantation was complicated by moderate acute cellular rejection as well as biliary obstruction requiring sphincterotomy and stent placement. After management of those complications, the patient's liver function tests returned to normal values and remained stable at her 6-month post-transplantation follow-up. This case shows that organ transplantation from a donor with a continuous-flow left ventricular assist device for a prolonged period can be performed successfully.

PMID: 29198691 [PubMed - in process]

Intraoperative Administration of 4-Factor Prothrombin Complex Concentrate Reduces Blood Requirements in Cardiac Transplantation.

Tue, 12/05/2017 - 13:45

Intraoperative Administration of 4-Factor Prothrombin Complex Concentrate Reduces Blood Requirements in Cardiac Transplantation.

J Cardiothorac Vasc Anesth. 2017 Aug 03;:

Authors: Sun GH, Patel V, Moreno-Duarte I, Zahedi F, Ursprung E, Couper G, Chen FY, Welsby IJ, Comenzo R, Kao G, Cobey FC

Abstract
OBJECTIVE: Assessing the efficacy of intraoperative 4-factor prothrombin complex concentrate (4F-PCC) use in blood product utilization, time to chest closure, intensive care unit (ICU) and hospital length of stay (LOS), thromboembolic complications, renal injury and mortality in left ventricular assist device (LVAD) patients on home anticoagulation therapy with warfarin, undergoing orthotopic heart transplantation (OHT).
DESIGN: Retrospective analysis of OHT patients at Tufts Medical Center from May 2013 to October 2016.
SETTING: Single-institution, university hospital setting.
PARTICIPANTS: Patients with preexisting LVADs who received orthotopic heart transplants (n = 74; 32 patients 4F-PCC, 42 patients no 4F-PCC).
INTERVENTIONS: Warfarin reversal using 4F-PCC in patients with LVADs undergoing orthotopic heart transplantation with the 4F-PCC dosing partitioned such that one-third was given pre-CPB and two-thirds were given post-CPB.
MEASUREMENTS AND MAIN RESULTS: The 4F-PCC group required less plasma (6 [IQR 4] v 1.31 [IQR 2] U, p < 0.001), cryoprecipitate (10 [IQR 10] v 7.50 [IQR 5] U, p < 0.001), and packed red blood cells (5 [IQR 4] v 2 [IQR 1.5] U, p < 0.001) and had a shorter time to chest closure (618.8 ± 111.4 v 547.9 ± 110.1 minutes, p = 0.008). There was no difference in platelet transfusion (2 [IQR 1] v 2 [IQR 1] U, p = 0.16), ICU or hospital LOS, acute kidney injury, or mortality. No thrombotic complications occurred.
CONCLUSIONS: Replacing plasma with 4F-PCC to reverse preoperative warfarin anticoagulation during OHT was associated with a shorter time to chest closure and less blood product utilization, without an increase in acute kidney injury, thromboembolic complications, or death.

PMID: 29198634 [PubMed - as supplied by publisher]

The role of HMGB1 in heart transplantation.

Tue, 12/05/2017 - 13:45

The role of HMGB1 in heart transplantation.

Immunol Lett. 2017 Nov 30;:

Authors: Lv Q, Li C, Mo Y, He L

Abstract
There has been significant progress in the field of heart transplantation over the last 45 years. Although the role of adaptive immunity in heart allograft rejection has been extensively studied for decades, there is increasing evidence that suggests that the innate immune system also contributes to the development of heart allograft rejection. The high-mobility group box (HMGB) proteins, particularly HMGB1, are self-derived innate immune activators that have multiple functions in the regulation of immunity and inflammation. Recent discoveries have illustrated the close link between HMGB1 and heart allograft rejection. In this review, we summarize current knowledge of the function of HMGB1 as a ligand that can evoke inflammatory responses and ultimately cause rejection after heart transplantation.

PMID: 29198620 [PubMed - as supplied by publisher]

Disease burden and costs from excess alcohol consumption, obesity, and viral hepatitis: fourth report of the Lancet Standing Commission on Liver Disease in the UK.

Tue, 12/05/2017 - 13:45

Disease burden and costs from excess alcohol consumption, obesity, and viral hepatitis: fourth report of the Lancet Standing Commission on Liver Disease in the UK.

Lancet. 2017 Nov 28;:

Authors: Williams R, Alexander G, Armstrong I, Baker A, Bhala N, Camps-Walsh G, Cramp ME, de Lusignan S, Day N, Dhawan A, Dillon J, Drummond C, Dyson J, Foster G, Gilmore I, Hudson M, Kelly D, Langford A, McDougall N, Meier P, Moriarty K, Newsome P, O'Grady J, Pryke R, Rolfe L, Rice P, Rutter H, Sheron N, Taylor A, Thompson J, Thorburn D, Verne J, Wass J, Yeoman A

Abstract
This report contains new and follow-up metric data relating to the eight main recommendations of the Lancet Standing Commission on Liver Disease in the UK, which aim to reduce the unacceptable harmful consequences of excess alcohol consumption, obesity, and viral hepatitis. For alcohol, we provide data on alcohol dependence, damage to families, and the documented increase in alcohol consumption since removal of the above-inflation alcohol duty escalator. Alcoholic liver disease will shortly overtake ischaemic heart disease with regard to years of working life lost. The rising prevalence of overweight and obesity, affecting more than 60% of adults in the UK, is leading to an increasing liver disease burden. Favourable responses by industry to the UK Government's soft drinks industry levy have been seen, but the government cannot continue to ignore the number of adults being affected by diabetes, hypertension, and liver disease. New direct-acting antiviral drugs for the treatment of chronic hepatitis C virus infection have reduced mortality and the number of patients requiring liver transplantation, but more screening campaigns are needed for identification of infected people in high-risk migrant communities, prisons, and addiction centres. Provision of care continues to be worst in regions with the greatest socioeconomic deprivation, and deficiencies exist in training programmes in hepatology for specialist registrars. Firm guidance is needed for primary care on the use of liver blood tests in detection of early disease and the need for specialist referral. This report also brings together all the evidence on costs to the National Health Service and wider society, in addition to the loss of tax revenue, with alcohol misuse in England and Wales costing £21 billion a year (possibly up to £52 billion) and obesity costing £27 billion a year (treasury estimates are as high as £46 billion). Voluntary restraints by the food and drinks industry have had little effect on disease burden, and concerted regulatory and fiscal action by the UK Government is essential if the scale of the medical problem, with an estimated 63 000 preventable deaths over the next 5 years, is to be addressed.

PMID: 29198562 [PubMed - as supplied by publisher]

First-in-Man Fully Percutaneous Complete Bypass of Heart and Lung.

Tue, 12/05/2017 - 13:45

First-in-Man Fully Percutaneous Complete Bypass of Heart and Lung.

JACC Cardiovasc Interv. 2017 Nov 18;:

Authors: Napp LC, Vogel-Claussen J, Schäfer A, Haverich A, Bauersachs J, Kühn C, Tongers J

PMID: 29198456 [PubMed - as supplied by publisher]

Case report and review of the literature: the utilisation of a ventricular assist device as bridge to recovery for anthracycline-induced ventricular dysfunction.

Tue, 12/05/2017 - 13:45

Case report and review of the literature: the utilisation of a ventricular assist device as bridge to recovery for anthracycline-induced ventricular dysfunction.

Cardiol Young. 2017 Dec 04;:1-5

Authors: Krasnopero D, Asante-Korang A, Jacobs J, Stapleton S, Carapellucci J, Dotson M, Stapleton G

Abstract
Ventricular assist devices are used in children with heart failure as a bridge to myocardial recovery or cardiac transplantation. Anthracyclines cause cardiac toxicity and may result in acute or long-term cardiac failure. We describe the use of a ventricular assist device as a bridge to recovery in a child with severe acute anthracycline-induced cardiomyopathy, and we review the associated literature. A 6-year-old girl was treated for acute myeloblastic leukaemia with daunorubicin and mitoxantrone. After 2 weeks her final dose of chemotherapy, her Left Ventricular Ejection Fraction decreased to 21%. Despite initiation of medical therapy, she had continued deterioration of left ventricular function and developed evidence of poor end-organ perfusion. She was not a candidate for cardiac transplantation, as the post-transplant immune suppression therapy would put her at risk for recurrence of her malignancy. We placed her on a short-term ventricular assist device as a bridge to ultimately placing her on a long-term ventricular assist device versus continuing medical therapy. Her left ventricular ejection fraction improved to 55% 24 days after ventricular assist device insertion. She was separated from the ventricular assist device 26 days after its insertion. She was discharged home 29 days later and is now 28 months after ventricular assist device implantation with stable ventricular function, as documented by a left ventricular ejection fraction of 55%, and normal end organ function. This case is one of the only reports known describing successful use of a short-term ventricular assist device as a bridge to recovery in a child with severe acute anthracycline-induced cardiotoxicity.

PMID: 29198224 [PubMed - as supplied by publisher]

Distinct Biomarker Profiles in Ex-Vivo T Cell Depletion Graft Manipulation Strategies: CD34+ Selection vs CD3+/19+ Depletion in Matched Sibling Allogeneic Peripheral Blood Stem Cell Transplantation.

Tue, 12/05/2017 - 13:45

Distinct Biomarker Profiles in Ex-Vivo T Cell Depletion Graft Manipulation Strategies: CD34+ Selection vs CD3+/19+ Depletion in Matched Sibling Allogeneic Peripheral Blood Stem Cell Transplantation.

Biol Blood Marrow Transplant. 2017 Nov 29;:

Authors: Cantilena CR, Ito S, Tian X, Jain P, Chinian F, Anandi P, Keyvanfar K, Draper D, Koklanaris E, Hauffe S, Superata J, Stroncek D, Muranski P, Barrett AJ, Battiwalla M

Abstract
Various approaches have been developed for ex vivo T cell depletion in allogeneic stem cell transplantation to prevent graft versus host disease (GVHD). However, direct comparisons between T-cell depletion strategies have not been well studied. We evaluated cellular and plasma biomarkers in two different graft manipulation strategies: CD3+CD19+ cell depletion (CD3/19D) versus CD34+ selection (CD34S) and their association with clinical outcomes. Identical conditions including the myeloablative preparative regimen, HLA-identical sibling donor, GVHD prophylaxis, and graft source were used for each cohort. Major clinical outcomes were similar between the two groups in terms of overall survival, non-relapse mortality, and cumulative incidence of relapse, however, the cumulative incidence of acute GVHD trended to be higher in CD3/19D compared to CD34S. A distinct biomarker profile was noted in the CD3/19D cohort: higher levels of ST2, impaired Helios- FoxP3+Tregs reconstitution, and rapid reconstitution of naïve, Th2, and Th17 CD4 cells in the early post-transplant period. In vitro graft replication studies confirmed that CD3/19D disproportionately depleted Tregs and other CD4 subset repertoires in the graft. This study confirmed the utility of biomarker monitoring which can be directly correlated to biological consequences and possible future therapeutic indications.

PMID: 29197677 [PubMed - as supplied by publisher]

Morphologic Findings in Donor (Transplanted) Hearts at Necropsy Early and Late After Orthotopic Heart Transplantation.

Tue, 12/05/2017 - 13:45

Morphologic Findings in Donor (Transplanted) Hearts at Necropsy Early and Late After Orthotopic Heart Transplantation.

Am J Cardiol. 2017 Oct 20;:

Authors: Roberts WC, Kondapalli N, Guileyardo JM

Abstract
Little necropsy information is available on donor hearts in place in recipients for varying periods. Necropsy studies were performed in 79 patients who had survived from 1 day to 17 years after orthotopic heart transplantation (OHT). At OHT, the 79 patients ranged in age from 3 to 70 years (mean 51), and at death, from 20 to 76 years (mean 54). The native hearts tended to be larger than the donor hearts in the 22 patients surviving ≤60 days and the donor hearts tended to be larger in the 57 patients surviving >60 days, suggesting that the donor hearts increased in weight with time. Cardiac adiposity increased with time. Grossly visible myocardial lesions were seen in 24 (30%) of the 79 cases: necrosis only in 20; fibrosis only in 2, and both in 2. One or more epicardial coronary arteries were narrowed >75% in cross-sectional area in 25 (32%), 1 of whom was in the group surviving ≤60 days. The right ventricular cavity was dilated in 73 cases (92%) and the left ventricular cavity in 39 cases. Evidence of graft rejection (lymphocytic infiltrates) was found in 50 patients (63%); in 8 (36%) of the 22 patients surviving ≤60 days, and in 42 (74%) of the 57 surviving >60 days. The lymphocytic infiltrates were largest in the subepicardial adipose tissue, next in myocardium, and least in endocardium. The quantity of the cellular infiltrates varied considerably among the patients. In conclusion, with time, the donor hearts tended to increase in weight, in the quantity of adipose tissue, in the amounts of coronary narrowing, in the frequency of ventricular cavity dilatation (particularly the right ventricle), and in the frequency of lymphocytic infiltrates (evidence of rejection).

PMID: 29197470 [PubMed - as supplied by publisher]

Autologous Bone Marrow Stem Cell Therapy in Patients With ST-Elevation Myocardial Infarction: A Systematic Review and Meta-analysis.

Tue, 12/05/2017 - 13:45
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Autologous Bone Marrow Stem Cell Therapy in Patients With ST-Elevation Myocardial Infarction: A Systematic Review and Meta-analysis.

Can J Cardiol. 2017 Dec;33(12):1611-1623

Authors: Jeyaraman MM, Rabbani R, Copstein L, Sulaiman W, Farshidfar F, Kashani HH, Qadar SMZ, Guan Q, Skidmore B, Kardami E, Ducas J, Mansour S, Zarychanski R, Abou-Setta AM

Abstract
BACKGROUND: Randomized controlled trials (RCTs) on bone marrow stem cell (BMSC) therapy in ST-elevation myocardial infarction (STEMI) patients have reported conflicting results. Our main objective was to critically appraise and meta-analyze best-available evidence on efficacy and safety of intracoronary administration of autologous BMSC therapy in STEMI patients after primary percutaneous coronary intervention.
METHODS: We conducted a search of MEDLINE, PubMed, EMBASE, CENTRAL, Global Health, CINAHL, and conference proceedings in February 2017. Our primary outcome was all-cause mortality. Secondary and safety outcomes included cardiac death, heart failure, arrhythmias, repeat myocardial infarction, or target vessel revascularizations; or improved health-related quality of life, left ventricular ejection fraction, or infarct size. Summary relative and absolute risks were obtained using random effects models. We also evaluated the strength of evidence.
RESULTS: A comprehensive database search identified 42 RCTs (3365 STEMI patients). BMSC therapy did not significantly decrease mortality (risk ratio, 0.71; 95% confidence interval, 0.45-1.11; I2, 0%; absolute risk reduction, 0.1%; 95% confidence interval, -0.71 to 0.91; 40 trials; 3289 participants; I2, 0%; low strength of evidence). BMSC therapy had no effect on secondary or adverse outcomes. Trial sequential analysis for all-cause mortality showed no evidence of a clinically important difference, with a very low probability that future studies can change the current conclusion.
CONCLUSIONS: On the basis of evidence from 42 RCTs published in the past 15 years, we provide conclusive evidence for a lack of beneficial effect for autologous BMSC therapy in patients with STEMI.

PMID: 29173601 [PubMed - indexed for MEDLINE]

Cardiac Support: Emphasis on Venoarterial ECMO.

Tue, 12/05/2017 - 13:45
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Cardiac Support: Emphasis on Venoarterial ECMO.

Crit Care Clin. 2017 Oct;33(4):777-794

Authors: King CS, Roy A, Ryan L, Singh R

Abstract
Major advances have been made in mechanical circulatory support in recent years. Venoarterial (VA) extracorporeal membrane oxygenation (ECMO) provides both pulmonary and circulatory support for critically ill patients with hemodynamic compromise, serving as a bridge to recovery or definitive therapy in the form of transplant or a durable ventricular assist device. In the past, VA ECMO support was used in cases of cardiogenic shock or failure to wean from cardiopulmonary bypass; however, the technology is now being applied to an ever-expanding list of conditions, including massive pulmonary embolism, cardiac arrest, drug overdose, and hypothermia.

PMID: 28887927 [PubMed - indexed for MEDLINE]

Sutureless aortic valve replacement in a calcified homograft combined with mitral valve replacement.

Tue, 12/05/2017 - 13:45
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Sutureless aortic valve replacement in a calcified homograft combined with mitral valve replacement.

J Cardiothorac Surg. 2017 Sep 07;12(1):82

Authors: Akca F, Lam K, Özdemir I, Tan E

Abstract
BACKGROUND: Aortic valve replacement in a patient with an aortic homograft can be very challenging, especially when concomitant mitral valve surgery needs to be performed.
CASE PRESENTATION: We report a case of implantation of a sutureless aortic valve bioprosthesis combined with mitral valve replacement in a patient with a severely calcified aortic homograft where conventional valve replacement was technically unfeasible.
CONCLUSIONS: We believe that sutureless AVR is a viable option especially for young patients with a high surgical risk where conventional valve replacement cannot be achieved.

PMID: 28882144 [PubMed - indexed for MEDLINE]

A dual therapy of off-pump temporary left ventricular extracorporeal device and amniotic stem cell for cardiogenic shock.

Tue, 12/05/2017 - 13:45
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A dual therapy of off-pump temporary left ventricular extracorporeal device and amniotic stem cell for cardiogenic shock.

J Cardiothorac Surg. 2017 Sep 07;12(1):80

Authors: Kazui T, Tran PL, Pilikian TR, Marsh KM, Runyan R, Konhilas J, Smith R, Khalpey ZI

Abstract
BACKGROUND: Temporary mechanical circulatory support device without sternotomy has been highly advocated for severe cardiogenic shock patient but little is known when coupled with amniotic stem cell therapy.
CASE PRESENTATION: This case reports the first dual therapy of temporary left ventricular extracorporeal device CentriMag with distal banding technique and human amniotic stem cell injection for treating a severe refractory cardiogenic shock of an 68-year-old female patient. A minimally-invasive off-pump LVAD was established by draining from the left ventricle and returning to the right axillary artery with distal arterial banding to prevent right upper extremity hyperperfusion. Amniotic stem cells were injected intramyocardially at the left ventricular apex, lateral wall, inferior wall, and right subclavian vein.
CONCLUSION: The concomitant use of the temporary minimally-invasive off-pump CentriMag placement and stem cell therapy not only provided an alternative to cardiopulmonary bypass and full-median sternotomy procedures but may have also synergistically enhanced myocardial reperfusion and regeneration.

PMID: 28882138 [PubMed - indexed for MEDLINE]

Cardiac Progenitor Cell Recruitment Drives Fetal Cardiac Regeneration by Enhanced Angiogenesis.

Tue, 12/05/2017 - 13:45
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Cardiac Progenitor Cell Recruitment Drives Fetal Cardiac Regeneration by Enhanced Angiogenesis.

Ann Thorac Surg. 2017 Dec;104(6):1968-1975

Authors: Zgheib C, Hodges MM, Allukian MW, Xu J, Spiller KL, Gorman JH, Gorman RC, Liechty KW

Abstract
BACKGROUND: In contrast to adults, the fetal response to myocardial infarction (MI) is regenerative, requiring the recruitment of cardiac progenitor cells to replace infarcted myocardium. Macrophage contribution to tissue repair depends on their phenotype: M1 are proinflammatory and initiate angiogenesis; M2a are profibrotic and contribute to blood vessels maturation; and M2c are proremodeling and proangiogenesis. The goal of the present study was to expand on this work by examining cardiac progenitor cells recruitment, and the role of macrophages in promoting angiogenesis and cardiac regeneration in the fetal heart after MI.
METHODS: Fetal and adult sheep underwent MI and were sacrificed 3 or 30 days after MI. Some fetal hearts received stromal cell-derived factor-1α-inhibitor treatment. The microvasculature was evaluated by micro-computed tomography, gene expression was evaluated by real-time polymerase chain reaction, and vessels counts were evaluated by immunohistochemistry.
RESULTS: Micro-computed tomography analysis showed restoration of microvasculature in fetal hearts after MI. Vascular endothelial growth factor-α increased, and the expression of tissue markers associated with the M1, M2a, and M2c macrophage phenotypes were elevated at day 3 after MI, but returned to baseline by 30 days after MI. In contrast, adult hearts after MI exhibited low vascular endothelial growth factor-α and persistent upregulation of all macrophage markers, consistent with prolonged inflammation, fibrosis, and remodeling. Inhibition of stromal cell-derived factor-1α in fetal infarcts prevented angiogenesis, decreased vascular endothelial growth factor-α, and was associated with a sustained increase in M1, M2a, and M2c markers after MI.
CONCLUSIONS: Changes in angiogenesis and macrophage phenotype-related gene expression after MI are important for the fetal regenerative response to MI and are mediated at least in part by cardiac progenitor cells recruitment.

PMID: 28821329 [PubMed - indexed for MEDLINE]

Cardiac Progenitor Cells Enhance Neonatal Right Ventricular Function After Pulmonary Artery Banding.

Tue, 12/05/2017 - 13:45
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Cardiac Progenitor Cells Enhance Neonatal Right Ventricular Function After Pulmonary Artery Banding.

Ann Thorac Surg. 2017 Dec;104(6):2045-2053

Authors: Wehman B, Pietris N, Bigham G, Siddiqui O, Mishra R, Li T, Aiello E, Jack G, Wang W, Murthi S, Sharma S, Kaushal S

Abstract
BACKGROUND: C-kit+ cardiac progenitor cells (CPCs) have been shown to be safe and effective in large-animal models and in an early-phase clinical trial for adult patients with ischemic heart disease. However, CPCs have not yet been evaluated in a preclinical model of right ventricular (RV) dysfunction, which is a salient feature of many forms of congenital heart disease.
METHODS: Human c-kit+ CPCs were generated from right atrial appendage biopsy specimens obtained during routine congenital cardiac operations. Immunosuppressed Yorkshire swine (6 to 9 kg) underwent pulmonary artery banding to induce RV dysfunction. Thirty minutes after banding, pigs received intramyocardial injection into the RV free wall with c-kit+ CPCs (1 million cells, n = 5) or control (phosphate-buffered saline, n = 5). Pigs were euthanized at 30 days postbanding.
RESULTS: Banding was calibrated to a consistent rise in the RV-to-systemic pressure ratio across both groups (postbanding: CPCs = 0.76 ± 0.06, control = 0.75 ± 0.03). At 30 days postbanding, the CPCs group demonstrated less RV dilatation and a significantly greater RV fractional area of change than the control group (p = 0.002). In addition, measures of RV myocardial strain, including global longitudinal strain and strain rate, were significantly greater in the CPCs group at 4 weeks relative to control (p = 0.004 and p = 0.01, respectively). The RV free wall in the CPCs group demonstrated increased arteriole formation (p < 0.0001) and less myocardial fibrosis compared with the control group (p = 0.02).
CONCLUSIONS: Intramyocardial injection of c-kit+ CPCs results in enhanced RV performance relative to control at 30 days postbanding in neonatal pigs. This model is important for further evaluation of c-kit+ CPCs, including long-term efficacy.

PMID: 28760475 [PubMed - indexed for MEDLINE]

Persistence and proliferation of human mesenchymal stromal cells in the right ventricular myocardium after intracoronary injection in a large animal model of pulmonary hypertension.

Tue, 12/05/2017 - 13:45
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Persistence and proliferation of human mesenchymal stromal cells in the right ventricular myocardium after intracoronary injection in a large animal model of pulmonary hypertension.

Cytotherapy. 2017 Jun;19(6):668-679

Authors: Badr Eslam R, Croce K, Mangione FM, Musmann R, Leopold JA, Mitchell RN, Waxman AB

Abstract
BACKGROUND AIMS: In this study, we demonstrate long-term persistence of human mesenchymal stromal cells (hMSCs) after intracoronary injection in a large animal model of pulmonary hypertension (PH).
METHODS: Commercially available placenta-derived hMSCs were used. Experiments were conducted on 14 female Yorkshire swine. Four animals served as controls, and 10 underwent pulmonary vein (PV) banding. After 12 ± 2 weeks, PH and PV dysfunction were confirmed by right heart catheterization and cardiac magnetic resonance imaging. hMSCs were injected in the marginal branch of the right coronary artery. Tissues were harvested 6, 9 or 24 days after infusion.
RESULTS: After 12 ± 2 weeks after PV banding, all subjects had increased mean pulmonary artery pressure (13.6 ± 3.6 versus 30.8 ± 4.5 mm Hg, P < 0.007) and a decrease in right ventricular ejection fraction from 51.7 ± 5.7% versus 30.5 ± 11.3% (P = 0.003). Intracoronary injection of hMSCs was well tolerated. Up to 24 days after hMSC injection, immunohistochemistry revealed extravascular viable human CD105+ mononuclear cells in the right ventricle (RV) that were Ki67+. This was confirmed by fluorescence in situ hybridization. CD45+ porcine inflammatory cells were identified, commonly seen adjacent to areas of healing microscopic infarction that likely dated to the time of the original hMSC injection. Anti-CD31 staining produced strong signals in areas of injected hMSCs. Immunohistochemistry staining for vascular cell adhesion molecule-1 showed upregulation in the clusters, where mononuclear cells were located.
CONCLUSIONS: hMSCs injected via intracoronary infusion survived up to 24 days and demonstrated proliferative capacity. hMSCs can persist long term in the RV and are potential cell source for tissue repair in RV dysfunction.

PMID: 28392314 [PubMed - indexed for MEDLINE]

Irx4 Marks a Multipotent, Ventricular-Specific Progenitor Cell.

Tue, 12/05/2017 - 13:45
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Irx4 Marks a Multipotent, Ventricular-Specific Progenitor Cell.

Stem Cells. 2016 Dec;34(12):2875-2888

Authors: Nelson DO, Lalit PA, Biermann M, Markandeya YS, Capes DL, Addesso L, Patel G, Han T, John MC, Powers PA, Downs KM, Kamp TJ, Lyons GE

Abstract
While much progress has been made in the resolution of the cellular hierarchy underlying cardiogenesis, our understanding of chamber-specific myocardium differentiation remains incomplete. To better understand ventricular myocardium differentiation, we targeted the ventricle-specific gene, Irx4, in mouse embryonic stem cells to generate a reporter cell line. Using an antibiotic-selection approach, we purified Irx4+ cells in vitro from differentiating embryoid bodies. The isolated Irx4+ cells proved to be highly proliferative and presented Cxcr4, Pdgfr-alpha, Flk1, and Flt1 on the cell surface. Single Irx4+ ventricular progenitor cells (VPCs) exhibited cardiovascular potency, generating endothelial cells, smooth muscle cells, and ventricular myocytes in vitro. The ventricular specificity of the Irx4+ population was further demonstrated in vivo as VPCs injected into the cardiac crescent subsequently produced Mlc2v+ myocytes that exclusively contributed to the nascent ventricle at E9.5. These findings support the existence of a newly identified ventricular myocardial progenitor. This is the first report of a multipotent cardiac progenitor that contributes progeny specific to the ventricular myocardium. Stem Cells 2016;34:2875-2888.

PMID: 27570947 [PubMed - indexed for MEDLINE]

Vascular stem cells-potential for clinical application.

Tue, 12/05/2017 - 13:45
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Vascular stem cells-potential for clinical application.

Br Med Bull. 2016 Jun;118(1):127-37

Authors: Slater SC, Carrabba M, Madeddu P

Abstract
INTRODUCTION: Cell therapy is a growing area of research as an alternative to pharmaceuticals or surgery for the treatment of ischaemic disease. Studies are focusing on delivering tissue-derived cells into damaged organs to promote vascular regeneration or gain of function.
SOURCES OF DATA: Pubmed, clinicaltrials.gov, BHF website.
AREAS OF AGREEMENT: Stem cells have the potential to become a viable treatment for many diseases, as indicated by the numerous pre-clinical studies demonstrating therapeutic benefit.
AREAS OF CONTROVERSY: The mechanisms of action for transplanted stem cells are still open to debate. Proposed mechanism includes direct cell incorporation and paracrine action. Additionally, the secretome produced by transplanted cells remains largely unknown.
GROWING POINTS: Initial studies focused on delivering stem cells by injection; however, current research is utilizing biomaterials to target cell delivery to specific areas.
AREAS TIMELY FOR DEVELOPING RESEARCH: Whilst stem cell research in the laboratory is expanding rapidly, transition into clinical studies is hindered by the availability of equivalent clinical grade reagents.

PMID: 27298231 [PubMed - indexed for MEDLINE]

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