Hybrid approach of ventricular assist device and autologous bone marrow stem cells implantation in end-stage ischemic heart failure enhances myocardial reperfusion

We challenge the hypothesis of enhanced myocardial reperfusion after implanting a left ventricular assist device together with bone marrow mononuclear stem cells in patients with end-stage ischemic cardiomyopathy. Irreversible myocardial loss observed in ischemic cardiomyopathy leads to progressive cardiac remodelling and dysfunction through a complex neurohormonal cascade. New generation assist devices promote myocardial recovery only in patients with dilated or peripartum cardiomyopathy. In the setting of diffuse myocardial ischemia not amenable to revascularization, native myocardial recovery has not been observed after implantation of an assist device as destination therapy. The hybrid approach of implanting autologous bone marrow stem cells during assist device implantation may eventually improve native cardiac function, which may be associated with a better prognosis eventually ameliorating the need for subsequent heart transplantation. The aforementioned hypothesis has to be tested with well-designed prospective multicentre studies

Rectus Sheath Hematoma: A Simplified Emergency Surgical Approach

Rectus sheath hematoma (RSH) is an uncommon clinical event usually associated with trauma or coagulation disorders. It can also occur spontaneously. RSH usually runs a benign course but it can present with hypovolemic shock. When conservative management fails, surgical exploration becomes mandatory. We propose a technique of emergency ligation of the inferior epigastric artery. This is a simple approach as this artery originates at the posterior rectus sheath above the inguinal ligament. This safe technique provides immediate hemodynamic stabilization

Multipotency and cardiomyogenic potential of human adipose-derived stem cells from epicardium, pericardium, and omentum

BACKGROUND: Acute myocardial infarction (MI) leads to an irreversible loss of proper cardiac function. Application of stem cell therapy is an attractive option for MI treatment. Adipose tissue has proven to serve as a rich source of stem cells (ADSCs). Taking into account the different morphogenesis, anatomy, and physiology of adipose tissue, we hypothesized that ADSCs from different adipose tissue depots may exert a diverse multipotency and cardiogenic potential. METHODS: The omental, pericardial, and epicardial adipose tissue samples were obtained from organ donors and patients undergoing heart transplantation at our institution. Human foreskin fibroblasts were used as the control group. Isolated ADSCs were analyzed for adipogenic and osteogenic differentiation capacity and proliferation potential. The immunophenotype and constitutive gene expression of alkaline phosphatase (ALP), GATA4, Nanog, and OCT4 were analyzed. DNA methylation inhibitor 5-azacytidine was exposed to the cells to stimulate the cardiogenesis. Finally, reprogramming towards cardiomyocytes was initiated with exogenous overexpression of seven transcription factors (ESRRG, GATA4, MEF2C, MESP1, MYOCD, TBX5, ZFPM2) previously applied successfully for fibroblast transdifferentiation toward cardiomyocytes. Expression of cardiac troponin T (cTNT) and alpha-actinin (Actn2) was analyzed 3 weeks after initiation of the cardiac differentiation. RESULTS: The multipotent properties of isolated plastic adherent cells were confirmed with expression of CD29, CD44, CD90, and CD105, as well as successful differentiation toward adipocytes and osteocytes; with the highest osteogenic and adipogenic potential for the epicardial and omental ADSCs, respectively. Epicardial ADSCs demonstrated a lower doubling time as compared with the pericardium and omentum-derived cells. Furthermore, epicardial ADSCs revealed higher constitutive expression of ALP and GATA4. Increased Actn2 and cTNT expression was observed after the transduction of seven reprogramming factors, with the highest expression in the epicardial ADSCs, as compared with the other ADSC subtypes and fibroblasts. CONCLUSIONS: Human epicardial ADSCs revealed a higher cardiomyogenic potential as compared with the pericardial and omental ADSC subtypes as well as the fibroblast counterparts. Epicardial ADSCs may thus serve as the valuable subject for further studies on more effective methods of adult stem cell differentiation toward cardiomyocytes

Study on the transformation of haematopoietic stem cells to cardiomyocytes in long term liquid culture

The aim of the study is to investigate the ability of bone marrow mesenchymal stem cells to differentiate toward cardiomyocytes in ligand culture. Bone marrow samples were aspirated from 30 patients undergoing open heart surgery. Mesenchymal stem cells were isolated and expanded in culture. Second passaged cells were treated with 10μΜ 5-azacytidine. Immunophenotype was detected with flow cytometry. Morphology was analyzed with contrast and electron microscopy. Vimentin and myosin heavy chain production were analyzed by immunohistochemistry. Expression of α-cardiac actin, b-myosin heavy chain and troponin-T was also analyzed with molecular studies. In treated cells, multiple myofilaments were detected that were positive immunohistochemically to myosin heavy chain. All studied genes were also expressed. In untreated cells not expanded in culture, all myocardial markers were negative.Σκοπός της παρούσας μελέτης αποτελεί η διερεύνηση της ικανότητας των αρχέγονων μεσεγχυματικών κυττάρων του μυελού των οστών να μετατρέπονται σε μυοκαρδιακά κύτταρα του μυελού των οστών να μετατρέπονται σε μυοκαρδιακά κύτταρα σε σύστημα υγρής καλλιέργειας. Δείγματα μυελού ελήφθησαν από 30 ασθενείς οι οποίοι υποβλήθηκαν σε χειρουργική επέμβαση ανοικτής καρδιάς. Τα μεσεγχυματικά βλαστικά κύτταρα απομονώθηκαν και τοποθετήθηκαν σε καλλιέργεια. Μετά τη δεύτερη ανακαλλιέργεια έγινε επίδραση 10μ.Μ 5-αζακυτιδίνης. Ο ανοσοφαινότυπος προσδιορίστηκε με κυτταρομετρία ροής. Η μελέτη της μορφολογίας διενεργήθηκε με το ανάστροφο καθώς και με το ηλεκτρονικό μικροσκόπιο. Πραγματοποιήθηκε ανοσοϊστοχημικός έλεγχος της βιμεντίνης και της βαριάς αλύσου της μυοσίνης. Μελετήθηκε παράλληλα η έκφραση των γονιδίων της α-καρδιακής ακτίνης και της β-βαριάς αλύσου της μυοσίνης και της τροπονίνης-Τ. Στα κύτταρα που υποβλήθηκαν στην επίδραση ανιχνεύτηκαν πολυάριθμα ινίδια, τα οποία ήταν θετικά με ανοσοϊστοχημεία στη βαριά άλυσο μυοσίνης. Παράλληλα διαπιστώθηκε έκφραση των υπό μελέτη γονιδίων. Αντίθετα, σε κύτταρα πολύ δεν υποβλήθηκαν σε καλλιέργεια, δε διαπιστώθηκε έκφραση μυοκαρδιακών δεικτών

Coronary artery bypass grafting with minimal versus conventional extracorporeal circulation; an economic analysis

Background: This study aims to develop a methodological framework for the comparative economic evaluation between Minimal Extracorporeal Circulation (MECC) versus conventional Extracorporeal Circulation (CECC) in patients undergoing coronary artery bypass grafting (CABG) in different healthcare systems. Moreover, we evaluate the cost-effectiveness ratio of alternative comparators in the healthcare setting of Greece, Germany, the Netherlands and Switzerland. Methods: The effectiveness data utilized were derived from a recent meta-analysis which incorporated 24 randomized clinical trials. Total therapy cost per patient reflects all resources expensed in delivery of therapy and the management of any adverse events, including drugs, diagnostics tests, materials, devices, blood units, the utilization of operating theaters, intensive care units, and wards. Perioperative mortality was used as the primary health outcome to estimate life years gained in treatment arms. Bias-corrected uncertainty intervals were calculated using the percentile method of non-parametric Monte-Carlo simulation. Results: TheMECC circuitwasmore expensive than CECC, with a difference ranging from 180 to _ 600 depending on the country. However, in terms of total therapy cost per patient the comparison favoredMECC in all countries. Specifically itwas associated with a reduction of _ 635 in Greece, _ 297 in Germany, _ 1590 in the Netherlands and _ 375 in Switzerland. In terms of effectiveness, the total life-years gained were slightly higher in favor of MECC. Conclusions: Surgery with MECC may be dominant (lower cost and higher effectiveness) compared to CECC in coronary revascularization procedures and therefore it represents an attractive new option relative to conventional extracorporeal circulation for CABG. (C) 2013 Elsevier Ireland Ltd. All rights reserved

Principles of Miniaturized ExtraCorporeal CirculationFrom Science and Technology to Clinical Practice /

XIX, 137 p. 75 illus., 66 illus. in color.online

Minimal invasive extracorporeal circulation should become the standard practice in coronary revascularization surgery†.

We read with great interest the large-scale network meta-analysis by Kowalewski et al. comparing clinical outcomes of patients undergoing coronary artery bypass grafting (CABG) operated on using minimal invasive extracorporeal circulation (MiECC) or off-pump (OPCAB) with those undergoing surgery on conventional cardiopulmonary bypass (CPB) [1]. The authors actually integrated into single study two recently published meta-analysis comparing MiECC and OPCAB with conventional CPB, respectively [2, 3] into a single study. According to the results of this study, MiECC and OPCAB are both strongly associated with improved perioperative outcomes following CABG when compared with CABG performed on conventional CPB. The authors conclude that MiECC may represent an attractive compromise between OPCAB and conventional CPB. After carefully reading the whole manuscript, it becomes evident that the role of MiECC is clearly undervalued. Detailed statistical analysis using the surface under the cumulative ranking probabilities indicated that MiECC represented the safer and more effective intervention regarding all-cause mortality and protection from myocardial infarction, cerebral stroke, postoperative atrial fibrillation and renal dysfunction when compared with OPCAB. Even though no significant statistical differences were demonstrated between MiECC and OPCAB, the superiority of MiECC is obvious by the hierarchy of treatments in the probability analysis, which ranked MiECC as the first treatment followed by OPCAB and conventional CPB. Thus, MiECC does not represent a compromise between OPCAB and conventional CPB, but an attractive dominant technique in CABG surgery. These results are consistent with the largest published meta-analysis by Anastasiadis et al. comparing MiECC versus conventional CPB including a total of 2770 patients. A significant decrease in mortality was observed when MiECC was used, which was also associated with reduced risk of postoperative myocardial infarction and neurological events [4]. Similarly, another recent meta-analysis by Benedetto et al. compared MiECC versus OPCAB and resulted in comparable outcomes between these two surgical techniques [5]. As stated in the text, superiority of MiECC observed in the current network meta-analysis, when compared with OPCAB, could be attributed to the fact that MiECC offers the potential for complete revascularization, whereas OPCAB poses a challenge for unexperienced surgeons; especially when distal marginal branches on the lateral and/or posterior wall of the heart need revascularization. This is reflected by a significantly lower number of distal anastomoses performed in OPCAB when compared with conventional CPB. Therefore, taking into consideration the literature published up to date, including the results of the current article, we advocate that MiECC should be integrated in the clinical practice guidelines as a state-of-the-art technique and become a standard practice for perfusion in coronary revascularization surgery