Biomedical subjects

Armin Welz

Publications and source records attributed to Armin Welz.

17 recordsLinked to original sources

PubMed2006

Engraftment of engineered ES cell-derived cardiomyocytes but not BM cells restores contractile function to the infarcted myocardium.

Cellular cardiomyoplasty is an attractive option for the treatment of severe heart failure. It is, however, still unclear and controversial which is the most promising cell source. Therefore, we investigated and examined the fate and functional impact of bone marrow (BM) cells and embryonic stem cell (ES cell)-derived cardiomyocytes after transplantation into the infarcted mouse heart. This proved particularly challenging for the ES cells, as their enrichment into cardiomyocytes and their long-term engraftment and tumorigenicity are still poorly understood. We generated transgenic ES cells expressing puromycin resistance and enhanced green fluorescent protein cassettes under control of a cardiac-specific promoter. Puromycin selection resulted in a highly purified (>99%) cardiomyocyte population, and the yield of cardiomyocytes increased 6-10-fold because of induction of proliferation on purification. Long-term engraftment (4-5 months) was observed when co-transplanting selected ES cell-derived cardiomyocytes and fibroblasts into the injured heart of syngeneic mice, and no teratoma formation was found (n = 60). Although transplantation of ES cell-derived cardiomyocytes improved heart function, BM cells had no positive effects. Furthermore, no contribution of BM cells to cardiac, endothelial, or smooth muscle neogenesis was detected. Hence, our results demonstrate that ES-based cell therapy is a promising approach for the treatment of impaired myocardial function and provides better results than BM-derived cells.

Animals↗

PubMed2006

Identification of "substrate fibrillators" and "trigger fibrillators" by pacemaker diagnostics.

BACKGROUND: The population of patients likely to respond to selected pacing algorithms for maintenance of sinus rhythm is unknown. OBJECTIVES: The purpose of this study was to identify patients with specific onset patterns of paroxysmal atrial fibrillation (AF). METHODS: Dual-chamber pacemakers with advanced diagnostic functions were implanted in 112 patients with conventional indications for antibradycardia pacing and a history of paroxysmal AF. Pacemaker diagnostic data were analyzed after 97.5 +/- 40.9 days. According to the frequency of premature atrial contractions (PACs) during the 5 minutes before AF onset, patients were assigned to one of three groups: group A (high PAC activity), group B (moderate PAC activity), or group C (low PAC activity). RESULTS: AF burden was lower in group A (4.6% +/- 2.4%) than group B (15.8% +/- 3.0%, P = .003) and group C (15.5% +/- 3.1%, P = .003). Fewer AF episodes occurred in group A (2.1 +/- 1.3 per day) than group B (3.8 +/- 1.2 per day, P = .006). Mean AF episode duration was shorter in group A (11.4 +/- 10.2 hours) than group C (41.4 +/- 27.5 hours, P = .03). CONCLUSION: The coincidence of low PAC activity before AF onset, high AF burden, and extended arrhythmia episode duration appears to be the consequence of a high atrial substrate factor. In these "substrate fibrillators," the efficacy of pacing algorithms for maintenance of sinus rhythm may be limited. In contrast, "trigger fibrillators" exhibiting low AF burden despite high PAC incidence may represent the target population for specific PAC-suppressing pacing algorithms.

Aged↗

PubMed2006

Individualized selection of pacing algorithms for the prevention of recurrent atrial fibrillation: Results from the VIP registry.

OBJECTIVES: The VIP registry investigated the efficacy of preventive pacing algorithm selection in reducing atrial fibrillation (AF) burden. BACKGROUND: There are few data identifying which patients might benefit most from which preventive pacing algorithms. METHODS: Patients, with at least one documented AF episode and a conventional antibradycardia indication for pacemaker therapy, were enrolled. They received pacemakers with AF diagnostics and four preventive algorithms (Selection and PreventAF series, Vitatron). A 3-month Diagnostic Phase with conventional pacing identified a Substrate Group (>70% of AF episodes with <2 premature atrial contractions [PACs] before AF onset) and a Trigger Group (< or =70% of AF episodes with <2 PACs before AF onset). This was followed by a 3-month Therapeutic Phase where in the Trigger Group algorithms were enabled aimed at avoiding or preventing a PAC and in the Substrate Group continuous atrial overdrive pacing was enabled. RESULTS: One hundred and twenty-six patients were evaluated. In the Trigger Group (n = 73), there was a statistically significant 28% improvement in AF burden (median AF burden: 2.06 hours/day, Diagnostic Phase vs 1.49 hours/day, Therapy Phase; P = 0.03304 signed-rank test), and reduced PAC activity. There was no significant improvement in AF burden in the Substrate Group (median AF burden: 1.82 hours/day, Diagnostic Phase vs 2.38 hours/day, Therapy Phase; P = 0.12095 signed-rank test), and little change in PAC activity. CONCLUSIONS: We identified a subgroup of patients for whom the selection of appropriate pacing algorithms, based on individual diagnostic data, translated into a reduced AF burden. Trigger AF patients were more likely responders to preventive pacing algorithms as a result of PAC suppression.

Aged↗

PubMed2005

Cells of primarily extra-valvular origin in degenerative aortic valves and bioprostheses.

AIMS: We assessed aortic valves from patients with non-rheumatic aortic valve stenosis (AS) and with degenerative aortic valve bioprostheses (BP) for the presence of progenitor cell and leukocyte subtype-specific markers. METHODS AND RESULTS: Diseased valve probes from a total of 87 patients (60 AS and 27 BP) were studied. We assessed presence and localization of endothelial progenitor cells (EPCs: CD34, CD133), dendritic cells (DCs: S100), T-lymphocytes (CD3), and macrophages (CD68) by immunohistochemical and morphometric analyses. In the majority of valves, we detected cell-bound signals of CD34 (48% of AS, 74% of BP, respectively), CD133 (58%/81%), S100 (58%/93%), CD3 (62%/81%), and CD68 (78%/93%). Labelled cells were predominantly localized within the valvular fibrosa. As key results, frequency of EPCs, DCs, macrophages, and lymphocytes was found significantly higher in BP when compared with AS (CD34: 19.2+/-23.2 vs. 5.7+/-13.0%; CD133: 13.7+/-12.4 vs. 5.5+/-8.3%; S100: 15.2+/-12.2 vs. 5.7+/-8.9%; CD3: 3.3+/-2.7 vs. 1.1+/-1.4%; CD68: 35.3+/-26.6 vs. 3.4+/-4.1%; each P<or=0.001). CONCLUSION: EPCs and DCs were detected in a large collective of degenerative aortic valves, more frequently in bioprostheses than in native cusps. Aortoluminal presence of these primarily extra-valvular cells co-localized with inflammatory cells is a novel key feature involved in aortic valve degeneration.

Aged↗

PubMed2005

Mechanical ventilation strategies and inflammatory responses to cardiac surgery: a prospective randomized clinical trial.

OBJECTIVE: To examine whether postoperative mechanical ventilation with lower tidal volumes (V(T)) has protective effects on inflammatory responses induced by cardiopulmonary bypass (CPB) surgery in smokers and nonsmokers. DESIGN AND SETTING: Prospective, randomized, controlled clinical trial in the intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: We examined 44 patients (22 smokers, 22 nonsmokers) immediately after uncomplicated CPB surgery. INTERVENTIONS: Ventilation was applied for 6 h with either V(T) of either 6 or 12 ml/kg ideal body weight. MEASUREMENTS AND RESULTS: The time course of serum tumor necrosis factor (TNF) alpha, interleukin (IL) 6, and IL-8 determined 0, 2, 4, and 6 h after randomization did not differ significantly between the ventilatory strategies. By contrast, in bronchoalveolar lavage fluids sampled after 6 h only TNF-alpha levels were significantly higher in the high V(T) group than the low V(T) group (50+/-111 pg/ml vs. 1+/-7 pg/ml). IL-6 and IL-8 concentrations did not differ between groups. Subgroup analysis of patients with serum TNF-alpha level higher than 0 pg/ml after surgery revealed lower TNF-alpha serum levels during lower V(T) ventilation. All observed effects were small, independent of patients' history of smoking, and were not correlated with duration of ventilation and ICU stay. CONCLUSIONS: Ventilation with lower V(T) had no or only minor effect on systemic and pulmonary inflammatory responses in patients with healthy lungs after uncomplicated CPB surgery. Our data do not suggest a clinical benefit of using low V(T) ventilation in these selected patients.

Aged↗

PubMed2005

Stem cell implantation in ischemic mouse heart: a high-resolution magnetic resonance imaging investigation.

Advances in the biology of stem cells have evoked great interest in cell replacement therapies for the regeneration of heart tissue after myocardial infarction. However, results from human trials are controversial, since the destination of the injected cells, their engraftment and their long-term fate have remained unclear. Here we investigate whether transplanted cells can be identified in the intact and lesioned murine myocardium employing high-resolution MRI. Cardiac progenitor cells, expressing the enhanced green fluorescent protein (EGFP), were labeled with ultra-small paramagnetic iron-oxide (USPIO) nanoparticles and transplanted into the intact or injured myocardium of mice. Their precise location was determined with high-resolution MRI and compared with histological tissue sections, stained with Prussian blue for iron content. These experiments showed that iron nanoparticle-loaded cells could be identified at high resolution in the mouse heart. However, ischemic myocardium (after cryoinjury or left coronary artery ligation) was characterized by a signal attenuation similar to that induced by USPIO-labeled cells in T2*-weighted MR images, making detection of labeled stem cells in this area by T2*-sensitive contrast rather difficult. In animals with myocardial injury only, the signal attenuated areas were of the same size in proton density- and T2*-weighted MR images. In injured animals also receiving labeled cells the lesioned area appeared larger in T2*--than in proton density-weighted MR images. This sequence-dependent lesion size change is due to the increased signal loss caused by the iron oxide nanoparticles, most sensitively detectable in the T2*-sensitive images. Thus, using the novel combination of these two parameter weightings, USPIO-labeled cells can be detected at high resolution in ischemic myocardium.

Animals↗

PubMed2003

Development of murine ischemic cardiomyopathy is associated with a transient inflammatory reaction and depends on reactive oxygen species.

We examined the effects of daily repetitive brief (15 min) myocardial ischemia and reperfusion (I/R) in WT C57BL6 and extracellular superoxide dismutase (EC-SOD)-overexpressing mice. In the absence of myocardial necrosis, I/R resulted in persistent fibrosis in ischemic areas of C57/BL6 mice associated with persistent global and segmental anterior wall dysfunction. The I/R protocol induced chemokines (peak 3 days) followed sequentially by infiltration of macrophages and myofibroblasts (5 days). Fibrosis peaked at 7 days and was stable at 28 days despite regression of the chemokine and cellular response. Discontinuation of I/R at 7 or 28 days led to regression of fibrosis and ventricular dysfunction. In contrast, the EC-SOD mice developed markedly less chemokine induction, cell response, and fibrosis, with no ventricular dysfunction. Reversible fibrosis and ventricular dysfunction are features of human hibernating myocardium. The reduction of the cellular and functional response in EC-SOD mice suggests a role for reactive O(2) in the pathogenesis of ischemic cardiomyopathy.

Animals↗

PubMed2003

A tumor necrosis factor gene polymorphism influences the inflammatory response after cardiac operation.

BACKGROUND: The genetic background may influence cytokine release evoked by cardiac operation. Thus we determined the allele frequency and genotype distribution of a bi-allelic tumor necrosis factor (TNF) gene polymorphism and TNF-alpha concentrations in patients undergoing cardiac operations with and without cardiopulmonary bypass (CPB). METHODS: The TNF NcoI gene polymorphism was identified by polymerase chain reaction followed by restriction analysis of the polymerase chain reaction product. Reading the size of the resulting DNA bands from the agarose gel defined the genotype as homozygous or heterozygous for the two alleles TNFB1 and TNFB2. Blood samples to determine TNF-alpha plasma levels were drawn from the patients before induction of general anesthesia after termination of CPB or after finishing coronary revascularization on the beating heart in non-CPB patients and 12 hours postoperatively. RESULTS: The genotype distribution and allele frequencies in 47 patients undergoing cardiac operation with CPB were comparable with those found in 36 patients undergoing cardiac operation without CPB. The TNF-alpha plasma levels over time were comparable in patients with and without CPB. However, patients homozygous for the TNF-B2 allele had significantly higher TNF-alpha plasma levels after termination of the CPB (40.2 +/- 3.5 pg/mL; mean +/- standard error of the mean; n = 28) compared with non-CPB patients (29.8 +/- 2.5 pg/mL; mean +/- standard error of the mean; n = 15) (p < 0.05). CONCLUSIONS: Patients homozygous for the TNF-B2 allele showed significantly higher TNF-alpha plasma levels after termination of CPB compared with non-CPB patients. Therefore preoperative TNF genotyping may be useful as patients with genetically determined increased proinflammatory cytokine expression with multiple comorbidities may in particular benefit from avoiding the use of CPB.

Adult↗

PubMed2003

Transit time flow measurement in on-pump and off-pump coronary artery surgery.

OBJECTIVE: Transit time flow measurement is frequently used during coronary artery bypass with and without cardiopulmonary bypass to detect graft dysfunction resulting from technical errors. METHODS: Intraoperative transit time flow measurement measurements of 896 patients requiring surgery for double- or triple-vessel disease were reviewed retrospectively. Six-hundred and ninety-five patients were operated on-pump (Group A: coronary artery bypass with cardiopulmonary bypass), and 201 patients off-pump (Group B: coronary artery bypass without cardiopulmonary bypass). Transit time flow measurement measurements were analyzed for mean flow (mL/min). In total, measurements of 2247 grafts were analyzed. RESULTS: Transit time flow measurement flows were lower in coronary artery bypass without cardiopulmonary bypass patients (left internal thoracic artery to left anterior descending artery: Group A, 37 [31, 40] mL/min vs Group B, 24 [20, 26] mL/min; saphenous vein graft to left anterior descending artery: Group A, 46.5 [40, 56] mL/min vs Group B, 21 [14, 57] mL/min. Troponin I release was reduced in the coronary artery bypass without cardiopulmonary bypass patients, with median values of 7.8 [7.0, 8.3] microg/L in Group A and 1.2 [0.9, 2.3] microg/L in Group B. CONCLUSION: Evaluation of transit time flow measurement is valuable in determining coronary graft patency after coronary artery bypass with cardiopulmonary bypass and coronary artery bypass without cardiopulmonary bypass. Decreased troponin I release suggests a myocardial benefit of coronary artery bypass without cardiopulmonary bypass compared to coronary artery bypass with cardiopulmonary bypass, although the intraoperative transit time flow measurement flow measurements are markedly lower.

Aged↗

PubMed2003

Can particulate extraction from the ascending aorta reduce neurologic injury in cardiac surgery?

OBJECTIVE: This study examined whether extraction of particulate emboli using intra-aortic filtration could decrease neurologic outcomes. METHODS: Patients (N = 582) were enrolled in a prospective, controlled study and alternately assigned to the therapy arm (n = 304; intra-aortic filtration) or control arm (n = 278). Preoperative, procedural, and postoperative data were collected. Neurologic examinations included the National Institutes of Health Stroke Scale, Glasgow Coma Scale, and memory tests. Investigators administering neurologic tests were blinded to the study arm. By the use of logistic regression and propensity matching, composite neurologic outcomes (transient ischemic attack, stroke, delirium, coma, and memory deficit) were evaluated. RESULTS: Patients in the filter group experienced a lower incidence of adverse neurologic outcomes than patients in the control group (4.3% vs 11.9%) (P <.001). There were significantly less transient ischemic attacks (0% vs 1.4%), delirium (3.0% vs 6.5%), and memory deficit (1.3% vs 6.2%). There were fewer strokes in the filter group compared with the control group (0.7% vs 2.2%), although the sample size was too small for a significant finding. Both groups experienced 1 coma outcome. The use of a filter was associated with an adjusted odds ratio of 0.375, implying that a patient who does not receive a filter is 2.7 times more likely to experience an adverse neurologic event. Logistic modeling also demonstrated that there are increasing chances of poor neurologic outcome with increasing age. The model indicates that there may be an increasing protective benefit from the filter with increasing age, although the interaction was not significant. CONCLUSIONS: The extraction of particulate emboli using intra-aortic filtration resulted in decreased neurologic outcomes.

Aged↗

PubMed2003

Advanced pacemaker diagnostic features in the characterization of atrial fibrillation: impact on preventive pacing algorithms.

Pacing algorithms to prevent PAF are mainly based on the suppression of premature atrial complexes (PACs), which play an important role in its initiation. In contrast to 24-hour ambulatory electrocardiograms, advanced pacemaker (PM) diagnostic features are capable of recording AF episodes during long follow-up periods and of characterizing AF in a detailed fashion. For the specific use of these algorithms, a detailed characterization of AF was performed in 91 dual chamber PM recipients with histories of AF. Fifteen patients with episodes of oversensing due to far-field signals or frequent episodes of "2:1-undersensing" of atrial flutter were excluded. The remaining 76 patients had high recurrence rates of AF (median 0.8 episodes/day), however, the majority of episodes lasted < 7 minutes. Despite frequent PACs (median 10.8/hour) during sinus rhythm, a median of 66.4% of the AF episodes were preceded by < 2 PACs/min before onset. In conclusion, frequent, short-lived AF episodes seem best suited for AF preventive pacing therapies. However, the small number of PACs preceding many AF episodes may limit the efficacy of PAC suppressing algorithms.

Algorithms↗

PubMed2003

Persistence of Chlamydia pneumoniae in degenerative aortic valve stenosis indicated by heat shock protein 60 homologues.

BACKGROUND AND AIMS OF THE STUDY: Based on the concept of chronic persistent infections with Chlamydia pneumoniae among variable stressors for aortic valve degeneration, the study aim was to assess the presence of chlamydial heat shock protein (cHSP) 60 and its human homologue (hHSP60) in diseased valvular tissue. METHODS: Surgical specimens of high-grade stenosed, native (n = 33) and bioprosthetic (n = 10) aortic valves were examined immunohistochemically for the localization of cHSP60, hHSP60 and macrophages (CD68), supplemented by polymerase chain reaction (PCR) and electron microscopy to prove microbial presence. RESULTS: Degenerated valves showed specific immunostaining of cHSP60 in 27 cases (65%), of hHSP60 in 26 (63%), and of CD68 in 36 (84%). Both HSP60 homologues were predominantly detected in valvular fibrosa, consistently co-localized with macrophages and, quantitatively, showed a strong correlation (r = 0.81, p < 0.001). Presence of C. pneumoniae was demonstrated by PCR in a subset of 11 of 18 valves (61%). Microbial persistence was confirmed by ultrastructural analysis. Degenerated prosthetic valves revealed markedly higher macrophage infiltration and cHSP60 signaling compared with degenerated native valves (each p < 0.05). CONCLUSION: Beyond detection of C. pneumoniae, the present data on co-localization and valvular predilection sites (fibrosa) of both HSP60 homologues indicate the presence of chronic persistent C. pneumoniae infection as well as regional stressor effects, and suggest their involvement in native and prosthetic valve degeneration.

Aged↗

PubMed2002

Cellular cardiomyoplasty improves survival after myocardial injury.

BACKGROUND: Cellular cardiomyoplasty is discussed as an alternative therapeutic approach to heart failure. To date, however, the functional characteristics of the transplanted cells, their contribution to heart function, and most importantly, the potential therapeutic benefit of this treatment remain unclear. METHODS AND RESULTS: Murine ventricular cardiomyocytes (E12.5-E15.5) labeled with enhanced green fluorescent protein (EGFP) were transplanted into the cryoinjured left ventricular walls of 2-month-old male mice. Ultrastructural analysis of the cryoinfarction showed a complete loss of cardiomyocytes within 2 days and fibrotic healing within 7 days after injury. Two weeks after operation, EGFP-positive cardiomyocytes were engrafted throughout the wall of the lesioned myocardium. Morphological studies showed differentiation and formation of intercellular contacts. Furthermore, electrophysiological experiments on isolated EGFP-positive cardiomyocytes showed time-dependent differentiation with postnatal ventricular action potentials and intact beta-adrenergic modulation. These findings were corroborated by Western blotting, in which accelerated differentiation of the transplanted cells was detected on the basis of a switch in troponin I isoforms. When contractility was tested in muscle strips and heart function was assessed by use of echocardiography, a significant improvement of force generation and heart function was seen. These findings were supported by a clear improvement of survival of mice in the cardiomyoplasty group when a large group of animals was analyzed (n=153). CONCLUSIONS: Transplanted embryonic cardiomyocytes engraft and display accelerated differentiation and intact cellular excitability. The present study demonstrates, as a proof of principle, that cellular cardiomyoplasty improves heart function and increases survival on myocardial injury.

Animals↗

PubMed2002

Cellular cardiomyoplasty in a transgenic mouse model.

BACKGROUND: Recent progress in the cardiotypic differentiation of embryonic and somatic stem cells opens novel prospects for the treatment of cardiovascular disorders. The aim of the present study was to develop a novel surgical approach that allows standardized cellular cardiomyoplasty in mouse with low-perioperative mortality. METHODS: Reproducible transmural lesions were generated by cryoinjury followed by intramural injection of embryonic cardiomyocytes using a newly designed holding device and vital dye staining. This approach was validated with a transgenic mouse model, in which the live reporter gene-enhanced green fluorescent protein (EGFP) is under control of a cardiac-specific promoter. RESULTS: The perioperative mortality was 10%. The engrafted EGFP-positive cardiomyocytes could be identified in a high percentage (72.2%, n=36) of operated animals. CONCLUSIONS: This novel approach enables reliable cellular replacement therapy in mouse and greatly facilitates the analysis of its molecular, cellular, and functional efficacy.

Animals↗

PubMed2002

An unusual case of pacemaker failure: complete disconnection of connector block and battery of a subpectorally implanted dual chamber pacemaker.

Local trauma to patients with implanted pacemaker devices may result in lead fracture or breakage of the lead socket with leakage of fluid into the connector system. This report describes an unusual case of complete entrance and exit block in a subpectorally implanted dual chamber pacemaker due to total disconnection and dislodgement of header block and battery part. Damage may be caused by an interaction of machine fatigue/manufacturing defective and fixation of the header with unusual movability of the battery, leading to breakage with intermittent malfunction and consecutive bradycardia and syncope.

Aged↗

PubMed2002

Radiofrequency catheter ablation of an incessant ventricular tachycardia following valve surgery.

Sustained monomorphic ventricular tachycardia (VT) after valve surgery represents a clinical entity with different tachycardia mechanisms. This case report describes an incessant VT after tricuspid and aortic valve replacement that did not respond to antiarrhythmic drug treatment. The tachycardia exhibited VA block and a right bundle branch block pattern with left-axis deviation, suggesting ventricular excitation via the left posterior fascicle. The electrophysiological study was limited by the prosthetic tricuspid and aortic valve replacement, therefore a transseptal approach was necessary to obtain access to the ventricular myocardium. Radiofrequency catheter ablation was performed in the proximal left bundle or distal His region with termination of the incessant VT followed by complete AV block. After pacemaker implantation using a transvenous right atrial and an epicardial ventricular lead, no VT reoccurrence could be documented.

Aortic Valve↗

PubMed2002

Off-pump coronary artery bypass (OPCAB) surgery.

During recent years, a rapid progress in the area of minimally invasive heart surgery has been seen. In addition to operations through smaller incisions and those without a complete median sternotomy, minimally invasive in cardiac surgery also means--and this might be even more important--performing the operation without cardiopulmonary bypass (CPB). Documented evidence indicates that CPB is an independent risk factor for end-organ injury after heart surgery. However, discussion continues regarding whether off-pump coronary artery bypass (OPCAB) techniques allow the same (or better) outcomes in long-term graft patency, myocardial damage, and associated morbidity compared with the classic operation done on CPB. That is one of the reasons the German insurance companies still do not accept OPCAB techniques as a viable alternative for surgical coronary revascularization, although the avoidance of CPB appears to have the greatest potential to minimize procedural costs and, consequently, provide economic benefit.

Cardiopulmonary Bypass↗