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Tomasz Siminiak

Publications and source records attributed to Tomasz Siminiak.

15 recordsLinked to original sources
PubMed2006

Postinfarction heart failure: surgical and trans-coronary-venous transplantation of autologous myoblasts.

Increasing experimental evidence indicates that skeletal myoblasts can be considered as a possible source of cells for regeneration of contractile performance in chronic postinfarction myocardial injury. In experimental models, the observed functional benefit of transplanting skeletal myoblasts into an area of chronic fibrotic myocardial scar has led to the development of clinical trials to evaluate the potential use of autologous skeletal myoblasts for myocardial regeneration in patients with postinfarction heart failure. We conducted an independent, phase I clinical trial to evaluate myoblast transplantation during coronary artery bypass grafting. In addition, to test whether the effect of transplanted cells on myocardial contractility was independent of revascularization, we performed a clinical study of percutaneous transvenous myoblast transplantation-the POZNAN trial. These trials have shown the feasibility of myoblast transplantation during cardiac surgery and via a percutaneous route, as well as the safety of both procedures when performed with concurrent prophylactic administration of amiodarone. Here, we review the details of our observations from both of these phase I clinical trials in the context of the clinical work in cardiovascular cell transplantation performed by others.

Cardiac Catheterization↗
PubMed2006

Catheter-based delivery of cells to the heart.

Clinical trials have begun to assess the feasibility, safety, and efficacy of administering progenitor cells to the heart in order to repair or perhaps reverse the effects of myocardial ischemia and injury. In contrast to surgical-based injections, which are often coupled with coronary bypass surgery, catheter-based injections are less invasive and make it possible to evaluate cell products used as sole interventions. The two methods that have been tested in humans are injecting cells directly into the ventricular wall with catheter systems dedicated to that purpose and infusing cells into coronary arteries with standard balloon angioplasty catheters. The catheters described in this article have been shown in both animal and clinical studies to be effective in cell delivery and to be safe. They are well-designed and user-friendly devices, but require further investigation to identify means for optimizing cell retention and to address other limitations. Randomized, placebo-controlled trials utilizing catheters for cell implantation are under way, and others are soon to follow. The results of these studies will help to shape the direction of future investigations, both clinical and basic. The spectrum of cardiac diseases, the variety of catheters for cell delivery, and the wide array of progenitor cell types open up this young field to creative discoveries.

Animals↗
PubMed2006

Monogenic hypercholesterolaemias--an evaluation of apolipoprotein B100 and LDL receptor gene polymorphisms.

INTRODUCTION: Normally the N-terminal domain of the LDL receptor (LDLR) binds to low-density lipoprotein through apolipoprotein B100. Mutations within the LDL receptor and/or apolipoprotein B-100 genes compromising this process may lead to congenital monogenic hypercholesterolaemias known as familial hypercholesterolaemia or familial defective apolipoprotein B-100. These diseases are inherited as autosomal dominant traits. AIM: To search for LDLR and apoB100 gene mutations in a Polish population of patients with hypercholesterolaemia and to determine their types and locations. An attempt was also made to evaluate the influence of identified gene mutations on the modification of protein product sequence and the severity of its functional impairment. METHODS: LDLR and apoB100 gene analyses using PCR, SSCP and automated sequencing techniques were performed in 190 hypercholesterolaemic patients. Flow cytometry was used to measure the influence of Cys152Trp mutation in the LDLR gene on ligand binding and internalisation. The OLA method was used for the preparation of adequate genetic markers allowing rapid detection of one of the most deleterious mutations of the apoB100 gene. RESULTS AND CONCLUSIONS: Three brand new mutations, not reported so far, have been detected--Pro2712Leu and Ile3532 in the apoB100 gene, and Cys347Ser in the LDLR gene--and numerous changes in the nucleotide sequence of the LDL receptor gene have been confirmed. The observations of functionality of the mutated receptor gene with flow cytometry suggested the dysfunction of LDLR due to Cys152Trp polymorphism reported in many studies.

Apolipoprotein B-100↗
PubMed2005

Percutaneous trans-coronary-venous transplantation of autologous skeletal myoblasts in the treatment of post-infarction myocardial contractility impairment: the POZNAN trial.

AIMS: Several experimental studies and the initial clinical experience have shown that autologous skeletal myoblast transplantation into the area of post-infarction left ventricular injury results in an increase in segmental contractile performance. This phase I clinical trial was designed to assess the feasibility and safety of autologous skeletal myoblast transplantation performed via a percutaneous trans-coronary-venous approach in patients with post-infarction left ventricular dysfunction. METHODS AND RESULTS: Ten patients with heart failure and presence of an akinetic or a dyskinetic post-infarction injury with no viable myocardium were included in the study. Skeletal myoblasts were obtained from a biopsy specimen and grown in cell culture. Patients were treated with prophylactic amiodarone infusion before and during the procedure, except one patient. Skeletal myoblast transplantations were performed uneventfully in nine patients using the TransAccess catheter system under fluoroscopic and intravascular ultrasound guidance. In one patient, the procedure was not performed because of the inability of appropriate coronary sinus guiding wire positioning across venous valve. In five patients, the anterior interventricular vein and in four patients, the middle cardiac vein were used to access the myocardium. Two to four intramyocardial injections 1.5-4.5 cm deep were performed in each patient, delivering up to 100 million cells in 0.4-2.5 mL of saline. During 6 months follow-up, New York Heart Association class improved in all patients and ejection fraction increased 3-8% in six out of nine cases. CONCLUSION: These data suggest the feasibility and procedural safety of myoblast transplantation performed via the trans-coronary-venous approach using the TransAccess catheter system.

Adult↗
PubMed2005

Incomplete stent apposition after implantation of paclitaxel-eluting stents or bare metal stents: insights from the randomized TAXUS II trial.

BACKGROUND: The clinical impact of late incomplete stent apposition (ISA) for drug-eluting stents is unknown. We sought to prospectively investigate the incidence and extent of ISA after the procedure and at 6-month follow-up of paclitaxel-eluting stents in comparison with bare metal stents (BMS) and survey the clinical significance of ISA over a period of 12 months. METHODS AND RESULTS: TAXUS II was a randomized, double-blind study with 536 patients in 2 consecutive cohorts comparing slow-release (SR; 131 patients) and moderate-release (MR; 135 patients) paclitaxel-eluting stents with BMS (270 patients). This intravascular ultrasound (IVUS) substudy included patients who underwent serial IVUS examination after the procedure and at 6 months (BMS, 240 patients; SR, 113; MR, 116). The qualitative and quantitative analyses of ISA were performed by an independent, blinded core laboratory. More than half of the instances of ISA observed after the procedure resolved at 6 months in all groups. No difference in the incidence of late-acquired ISA was observed among the 3 groups (BMS, 5.4%; SR, 8.0%; MR, 9.5%; P=0.306), with a similar ISA volume (BMS, 11.4 mm3; SR, 21.7 mm3; MR, 8.5 mm3; P=0.18). Late-acquired ISA was the result of an increase of vessel area without change in plaque behind the stent. Predictive factors of late-acquired ISA were lesion length, unstable angina, and absence of diabetes. No stent thrombosis occurred in the patients diagnosed with ISA over a period of 12 months. CONCLUSIONS: The incidence and extent of late-acquired ISA are comparable in paclitaxel-eluting stents and BMS. ISA is a pure IVUS finding without clinical repercussions.

Aged↗
PubMed2005

The Allan factor: a new model of mathematical interpretation of heart rate variability in stable coronary artery disease. Preliminary results.

INTRODUCTION: The current analysis of heart rate variability (HRV) is one of the noninvasive methods of cardiovascular system assessment. The quantitative characteristics of the RR interval sequence and its dynamics are still under development as regards measurement techniques and development of new HRV interpretation models. The practical clinical application of the standard measurements is still insufficient and improvement of sensitivity and specificity of HRV parameters is needed. AIM: To assess a novel mathematical model of HRV interpretation and compare it with standard HRV measurements for patients with stable coronary artery disease (CAD), based on the virtual instrumentation technique. METHODS: The study group consisted of 24 patients with CAD confirmed by coronary angiography and a control group of 15 volunteers. Short-term electrocardiographic signals were recorded by a computer system and analysed for estimation of several HRV descriptors in time, frequency and combined time-frequency domains. Calculations included standard HRV measures and the Allan factor, a parameter based on the Haar wavelet transform. RESULTS: None of the investigated measurements derived from power spectral analysis has shown a statistically significant difference between healthy controls and patients with CAD, with the exception of rMSSD (Wilcoxon test: supine position *p=0.0018, erect position p=0.0708; discriminant function analysis: supine position *p=0.0069, erect position p=0.7851). Compared with standard HRV variables, the Allan factor better discriminated patients with CAD from healthy subjects (Wilcoxon test: supine position *p=0.0172, erect position *p=0.0001; discriminant function analysis: supine position p=0.8962, erect position *p=0.0200). CONCLUSIONS: The observations related to the novel parameter based on combined time and frequency domains may provide better quantitative measurements of heart rate variability in patients with coronary artery disease and require further investigations to assess their sensitivity and specificity.

Adult↗
PubMed2004

Autologous skeletal myoblast transplantation for the treatment of postinfarction myocardial injury: phase I clinical study with 12 months of follow-up.

BACKGROUND: Experimental studies have shown that skeletal myoblast transplantation into an area of postinfarction left ventricular injury results in an increase of segmental contractile performance that could be related to transplanted myoblasts. Initial experience with autologous skeletal myoblast transplantation in patients with postinfarction myocardial injury has also been obtained. METHODS: Patients who survived an acute myocardial infarction and were scheduled to undergo coronary artery bypass grafting were screened by means of dobutamine stress echocardiography and included into the study when no contractility changes within akinetic/dyskinetic segments were observed. Ten patients who gave informed consent were enrolled, and autologous myoblasts (satellite cells) were isolated from the skeletal muscle biopsy. Myoblast injections into the akinetic/dyskinetic area were performed after constriction of the anastomoses during the coronary artery bypass grafting procedure. RESULTS: Myoblast transplantations were performed after 3 weeks of in vitro culture in all patients. One patient died of a recent infarction at day 7 postoperatively because of a recent infarction in a remote area of the left ventricle. The left ventricular ejection fraction increased from 25% to 40% (mean, 35.2%) before the procedure to 29% to 47% (mean, 42.0%) during the 4-month visit (P <.05), and the effect was maintained throughout 12 months of follow-up. Sustained ventricular tachycardia was observed in 2 patients in the early postoperative period and in the other 2 patients after 2 weeks of follow-up. Prophylactic amiodarone infusion was used in the remaining 8 patients and prevented sustained ventricular tachycardia episodes. CONCLUSIONS: Autologous skeletal myoblast transplantation for the treatment of postinfarction heart failure is feasible. Our initial observations justify further research to validate this method in a clinical practice.

Cells, Cultured↗
PubMed2004

Autologous skeletal myoblasts for myocardial regeneration.

We overview the current knowledge about the use of skeletal myoblasts in regeneration of infarcted myocardium. Myoblasts are attractive candidates for cell source for cardiomyoplasty in chronic postmyocardial injury as indicated by experimental and initial clinical experience. We also review the recent developments in skeletal myoblasts transplantation techniques with special attention to percutaneous transvenous approach to deliver therapeutic agents into myocardium from the lumen of coronary veins under intravascular guidance.

Arrhythmias, Cardiac↗
PubMed2003

Transcardiac release of soluble adhesion molecules during coronary artery bypass grafting: effects of crystalloid and blood cardioplegia.

BACKGROUND: Dysfunction of myocardium as a result of ischemia/reperfusion during coronary artery bypass grafting (CABG) is currently one of the biggest problems in cardiovascular surgery. In previous studies, it has been well established that activated leukocytes and coronary vascular endothelial cells play an important role in the development of cardiac tissue damage during ischemia followed by reperfusion. Interactions between both of these cell types require the expression of adhesion molecules on their surface. In certain conditions, on cell activation, the adhesion proteins may be released from activated cells in soluble form into circulation. The purpose of our study was to establish whether the use of blood cardioplegia modifies plasma levels of soluble intracellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), and soluble L-selectin (sL-selectin) in comparison with crystalloid cardioplegia in patients undergoing CABG. METHODS: Patients undergoing CABG were classified into two groups to receive cold crystalloid cardioplegia (St. Thomas' Hospital) or cold blood cardioplegia (method of Buckberg), followed by a "warm-shot" of the solution. Coronary sinus and arterial blood samples were obtained from 50 patients (42 men and 8 women; age range, 34 to 73 years) before aortic cross-clamping, at the beginning of reperfusion, and after 30 min of reperfusion. Plasma levels of soluble adhesion molecules were measured using sensitive enzyme-linked immunosorbent assays. RESULTS: The transcardiac release of sICAM-1 and sVCAM-1 following myocardial ischemia/reperfusion during CABG was evident in both groups of patients. However, the increase of soluble forms of both of these adhesion proteins was more significant in the group of patients receiving crystalloid cardioplegia. Crystalloid cardioplegia resulted in decreased plasma level of sE-selectin in the coronary sinus blood sample after 30 min of reperfusion. No significant changes in plasma levels of sL-selectin in either group were observed. CONCLUSION: Cardioplegia may affect the release of soluble forms of adhesion molecules from ischemic myocardium and modify endothelium activation in patients undergoing CABG.

Adult↗
PubMed2003

Percutaneous autologous myoblast transplantation in the treatment of post-infarction myocardial contractility impairment--report on two cases.

Numerous animal experimental studies as well as the initial human experience have shown that autologous skeletal myoblast transplantation into area of post-infarction left ventricular injury results in an increase in segmental contractile performance related to contraction of cells differentiated from transplanted myoblasts. We have previously introduced skeletal myoblast transplantation performed at the time of coronary artery bypass grafting. Currently, we report the first two cases in Poland of percutaneous autologous myoblast transplantation in the treatment of post-infarction heart failure. The procedures were performed using a catheter system enabling intra-myocardial injections from the lumen of cardiac veins under intravascular ultrasound guidance. Lack of major procedural complications and expected benefits from myocardial regeneration in patients with post-infarction heart failure justify initiation of phase one clinical trial to evaluate this method.

Biopsy↗
PubMed2003

Autologous bone marrow stem cell transplantation in acute myocardial infarction-report of two cases.

The results of numerous experimental and clinical studies evaluating transplantation of bone marrow-derived pluripotential stem cells into the area of postinfarction myocardial injury, including direct myocyte precursors, are very encouraging. We have previously reported our clinical experience with transplantation of autologous skeletal myoblasts in the treatment of postinfarction myocardial injury. Currently, we report on two cases of intracoronary autologous bone marrow - derived CD34+ stem cells transplantation during acute phase of myocardial infarction. Lack of major procedural complication and expected benefits resulting from myocardial regeneration justify the initiation of a clinical study evaluating the use of this method in the treatment of patients with myocardial infarction. Our current report is only a method description and the two first cases presentation, indicating its feasibility - evaluation of the efficacy requires future investigations.

Adult↗