Restitution of the Infarcted Myocardium- the Role of Stem Cells

Even after optimal reperfusion strategies implementing percutaneous coronary intervention (PCI) with stent implantation and modern medical regimen for patients with acute myocardial infarction, myocardial salvage is often incomplete and adverse ventricular remodeling with subsequent heart failure develops. The transplantation of autologous bone marrow stem cells (BM-SCs) via the intracoronary delivery route after PCI of the infarct related artery (IRA) has been investigated in several observational studies which proved the safety and feasibility of the method. The results of the randomized studies were rather controversial. The BOOST study (Bone Marrow transfer to enhance ST-elevation infarction regeneration) was the first randomized study with patients receiving either bone-marrow derived mononuclear cells or placebo 5 days after primary PCI. The improvement of the ejection fraction reported in the cell infusion group at 6 months was attenuated during a follow-up study of 18 months. Of note, a similar restenosis rate (13%) was reported between the 2 groups

Stem Cells and Cardiac Repair

Contrary to the initial belief that the heart is a terminally differentiated organ that cannot replace its own cell damage, there is now proof that the circulating blood provides the injured tissue with adult stem and progenitor cells, which have the potential to differentiate into cardiomyocytes and ultimately improve cardiac function. Thus, transplantation of stem cells into the myocardium in patients with severe myocardial dysfunction post-myocardial infarction is being currently investigated for experimental as well as for clinical purposes. Many issues regarding the mode of action remain to be elucidated. The BOOST trial was the first completed, randomized study that showed safety, feasibility and efficacy of the method. However, a more recent doubleblind, placebo-controlled study failed to reveal an increase in global left ventricular nejection fraction and cast doubt on the efficacy of the method. Thus, further randomized studies are needed to evaluate this novel approach in the treatment of ischemic heart failure and determine its role, safety and efficacy

Intracoronary infusion of selected some marrow stem cells in patients with heart failure

The autologous transplantation of stem cells for cardiac repair is currently being investigatedas a potential treatment modality for patients with coronary artery disease. The rationale of thisnovel method is the enhancement of the natural repair mechanisms performed by tissue-specificand circulating stem/ progenitor cells. Contrary to the dogma that the heart is a terminallydifferentiated organ that cannot replace its own cell damage, there is now proof from preclinicalstudies that the circulating blood provides the injured tissue with adult stem and progenitorcells, which have the potential to differentiate into multiple cell lineages and ultimately improvecardiac function. Many questions regarding the exact mode of action remain unanswered.Most of the randomized controlled clinical studies conducted so far pertain to patients afterprimary percutaneous coronary intervention for acute myocardial infarction whereas patientswith chronic myocardial infarction or chronic myocardial ischemia have been studied mostlyin observational studies.The aim of our study was to test the safety and efficacy of intracoronary administration ofselected CD133+ and CD133-CD34+ bone marrow-derived bone marrow stem cells in patientswith old anterior, non viable myocardial infarction and abnormal ventricular function. Twenty fourpatients with old anterior non-viable myocardial infarction and left ventricular ejection fraction at baseline 95%), ενώ το ποσοστό επισήμανσης μετρήθηκε σε 30%. Μετά από εν-δοστεφανιαία έγχυση ενός μεγάλου αριθμού κυττάρων παρατηρήθηκε προσκόλληση τους στηνεμφραγματική περιοχή σε ποσοστό 9.2±3.6 % την πρώτη ώρα (8 ασθενείς) και 6.8±2.4 % στις24 ώρες (1 ασθενής) μετά την επέμβαση, ενώ τα υπόλοιπα επισημασμένα κύτταρα απεικονίστη-καν στο ήπαρ, στον σπλήνα, στους πνεύμονες και στον εντερικό σωλήνα.Φαίνεται λοιπόν ότι η ενδοστεφανιαία χορήγηση επιλεγμένων κυττάρων μυελού των οστώνμε το αντιγόνο επιφανείας CD133+ και CD133-CD34+ έχει θετική δράση στην κοιλιακή αναδια-μόρφωση, στην αιμάτωση της εμφραγματικής περιοχής και στις ιστικές ταχύτητες καθώς και τηνεπιμήκη παραμόρφωση της εμφραγματικής περιοχής. Αν και η μελέτη μας αφορούσε ασθενείςμε παλαιό έμφραγμα μυοκαρδίου και συνεπακόλουθη ελαττωμένη – σε σχέση με την οξεία αντί-δραση στην άμεση μετεμφραγματική περίοδο- χημειοπροσέλκυση προγονικών κυττάρων δείξα-με ότι τα χορηγηθέντα κύτταρα μεταναστεύουν στην εμφραγματική περιοχή και συγκρατούνταισε ικανό ποσοστό έως και 24 ώρες μετά την έγχυση.Πολλές κλινικές μελέτες ανέφεραν την ασφάλεια και αποτελεσματικότητα της κυτταρικής μυο-καρδιοπλαστικής σε ασθενείς μετά από οξύ έμφραγμα μυοκαρδίου, χρόνια μυοκαρδιακή ισχαιμία(χωρίς δυνατότητα επαναγγείωσης) και ισχαιμική καρδιακή ανεπάρκεια. Η βελτίωση της καρδιακής λειτουργίας αποδείχθηκε στις περισσότερες από αυτές παρά την ανομοιογένεια στο είδος τωνκυττάρων που χρησιμοποιήθηκαν, στο σχεδιασμό τους και στις παθήσεις που εκτιμήθηκαν. Σχετικάμε την αποτελεσματικότητα της μεθόδου παρατηρήθηκε στις περισσότερες μελέτες μικρή αύξη-ση του κλάσματος εξώθησης, μικρή μείωση της εμφραγματικής περιοχής και ευεργετική δράσηστην κοιλιακή αναδιαμόρφωση με αμφίβολο όμως κλινικό όφελος στην επιβίωση ή/και θνητότητατων ασθενών αυτών. Σίγουρα όμως δεν παρατηρήθηκε στην κλινική έρευνα το όφελος στην καρ-διακή λειτουργία που θα περίμενε κανείς μετά τα εντυπωσιακά δεδομένα που ήρθαν από πολλέςπειραματικές εργασίες. Προς αυτήν την κατεύθυνση κινήθηκε και το Task Force της ΕυρωπαϊκήςΚαρδιολογικής Εταιρείας το έτος 2006 που συνέστησε τη χρήση αυστηρών και προκαθορισμένωνκριτηρίων εισαγωγής και αποκλεισμού των ασθενών στις κλινικές μελέτες που διεξάγονται με τηχρήση αυτόλογων στελεχιαίων κυττάρων. Για το λόγο αυτό διενεργούνται πλέον μεγάλες τυχαι-οποιημένες πολυκεντρικές μελέτες με σκοπό να απαντηθούν βασικά ερωτήματα στην κυτταρικήμυοκαρδιοπλαστική πριν μπορέσει να χρησιμοποιηθεί ευρέως στην κλινική πράξη

Percutaneous transcatheter closure of aorto-right ventricular fistula using the Amplatzer duct occluder

The occurrence of aorto-right ventricular fistula after an aortic valve replacement is rare. If it remains untreated, this condition can result in heart failure and could thus significantly compromise patient survival. Surgical closure is the treatment of choice; however, transcatheter closure has been attempted with relatively acceptable results. Here, we report on a patient who presented with heart failure with an aorto-right ventricular fistula that was present for nine years following aortic valve replacement. Successful transcatheter closure of the fistula with the use of the Amplatzer duct occluder was performed, suggesting that the percutaneous approach is an efficient technique for the treatment of such fistulae

Experimental Investigation of Polypropylene Composite Drawn Fibers with Talc, Wollastonite, Attapulgite and Single-Wall Carbon Nanotubes

Isotactic polypropylene (PP) composite drawn fibers were prepared using melt extrusion and high-temperature solid-state drawing at a draw ratio of 7. Five different fillers were used as reinforcement agents (microtalc, ultrafine talc, wollastonite, attapulgite and single-wall carbon nanotubes). In all the prepared samples, antioxidant was added, while all samples were prepared with and without using PP grafted with maleic anhydride as compatibilizer. Material characterization was performed by tensile tests, differential scanning calorimetry, thermogravimetric analysis and Fourier transform infrared spectroscopy. Attapulgite composite fibers exhibited poor results in terms of tensile strength and thermal stability. The use of ultrafine talc particles yields better results, in terms of thermal stability and tensile strength, compared to microtalc. Better results were observed using needle-like fillers, such as wollastonite and single-wall carbon nanotubes, since, as was previously observed, high aspect ratio particles tend to align during the drawing process and, thus, contribute to a more symmetrical distribution of stresses. Competitive and synergistic effects were recognized to occur among the additives and fillers, such as the antioxidant effect being enhanced by the addition of the compatibilizer, while the antioxidant itself acts as a compatibilizing agent

Optimization of Thermal and Mechanical Properties of Polypropylene-Wollastonite Composite Drawn Fibers Based on Surface Response Analysis

The thermal and mechanical properties of polypropylene-wollastonite composite drawn fibers were optimized via experiments selected with the Box-Behnken approach. The drawing ratio, the filler and the compatibilizer content were chosen as design variables, while the tensile strength, the melting enthalpy and the onset decomposition temperature were set as response variables. Drawn fibers with tensile strength up to 535 MPa were obtained. Results revealed that the drawing ratio is the most important factor for the enhancement of tensile strength, followed by the filler content. All the design variables slightly affected the melting temperature and the crystallinity of the matrix. Also, it was found that the addition of polypropylene grafted with maleic anhydride as compatibilizer has a multiple effect on the final properties, i.e., it induces the dispersion of both the antioxidant and the filler, tending to increase thermal stability and tensile strength, while, on the same time, deteriorates mechanical and thermal properties due to its lower molecular weight and thermal stability. Such behavior does not allow for simultaneous maximization of thermal stability and tensile strength. Optimization based on a compromise, i.e., targeting maximization of tensile strength and onset decomposition temperature higher than 300 °C, yields high desirability values and predictions in excellent agreement with verification experiments

Surface Response Analysis for the Optimization of Mechanical and Thermal Properties of Polypropylene Composite Drawn Fibers with Talc and Carbon Nanotubes

A large portion of the produced Polypropylene (PP) is used in the form of fibers. In this industrially oriented study, the development of composite PP drawn fibers was investigated. Two types of fillers were used (ultra-fine talc and single-wall carbon nanotubes). Optimization of the thermal and mechanical properties of the produced composite drawn fibers was performed, based on the Box-Behnken design of experiments method (surface response analysis). The effect of additives, other than the filler, but typical in industrial applications, such as an antioxidant and a common compatibilizer, was investigated. The drawing ratio, the filler, and the compatibilizer or the antioxidant content were selected as design variables, whereas the tensile strength and the onset decomposition temperature were set as response variables. Fibers with very high tensile strength (up to 806 MPa) were obtained. The results revealed that the maximization of both the tensile strength and the thermal stability was not feasible for composites with talc due to multiple interactions among the used additives (antioxidant, compatibilizer, and filler). Additionally, it was found that the addition of talc in the studied particle size improved the mechanical strength of fibers only if low drawing ratios were used. On the other hand, the optimization targeting maximization of both tensile strength and thermal stability was feasible in the case of SWCNT composite fibers. It was found that the addition of carbon nanotubes improved the tensile strength; however, such improvement was rather small compared with the tremendous increase of tensile strength due to drawing

Monitoring of Levosimendan Administration in Patients with Pulmonary Hypertension Undergoing Cardiac Surgery and Effect of Two Different Dosing Schemes on Hemodynamic and Echocardiographic Parameters

Introduction: The perioperative management of patients with pulmonary hypertension (PH) undergoing cardiac surgery represents one of the most challenging clinical scenarios. This fact mainly depends on the relationship existing between PH and right ventricular failure (RVF). Levosimendan (LS) is an inodilator that might be an effective agent in the treatment of PH and RVF. The aim of this study was to examine the impact of the duration of cardiopulmonary bypass (CPB) on the therapeutic drug monitoring of LS and to evaluate the effect of preemptive administration of LS on perioperative hemodynamic and echocardiographic parameters in cardiac surgical patients with preexisting PH. Materials and Methods: In this study, LS was administered in adult patients undergoing cardiac surgery before CPB in order to prevent exacerbation of preexisting PH and subsequent right ventricular dysfunction. Thirty cardiac surgical patients with preoperatively confirmed PH were randomized to receive either 6 μg/kg or 12 μg/kg of LS after the induction of anesthesia. The plasma concentration of LS was measured after CPB. In this study, a low sample volume was used combined with a simple sample preparation protocol. The plasma sample was extracted by protein precipitation and evaporated; then, the analyte was reconstituted and detected using specific and sensitive bioanalytical liquid chromatography with mass spectrometry (LC-MS/MS) methodology. The clinical, hemodynamic, and echocardiographic parameters were registered and evaluated before and after the administration of the drug. Results: A fast bioanalytical LC-MS/MS methodology (a run time of 5.5 min) was developed for the simultaneous determination of LS and OR-1896, its main metabolite in human plasma. The LC-MS/MS method was linear over a range of 0.1–50 ng/mL for LS and 1–50 ng/mL for its metabolite OR-1896. Measured plasma concentrations of LS were inversely related to the duration of CPB. LS administration before CPB during cardiac surgery was effective in reducing pulmonary artery pressure and improving hemodynamic parameters after CPB, with a more pronounced and durable effect of the drug at the dose of 12 μg/kg. Additionally, administration of LS at a dose of 12 μg/kg in cardiac surgical patients with PH before CPB improved right ventricular function. Conclusion: LS administration decreases pulmonary artery pressure and may improve right ventricular function in patients with PH undergoing cardiac surgery