Effect of freshly isolated autologous tissue resident stromal cells on cardiac function and perfusion following acute myocardial infarction.

BACKGROUND: The aim of this study was to investigate the effect of intracoronary administration of freshly isolated, uncultured autologous tissue-derived stromal cells on cardiac function and perfusion after acute infarction in pigs. METHODS: A transmural myocardial infarction in a porcine model was induced by occlusion of the mid LAD with an angioplasty balloon for 3 h. Upon reperfusion, freshly isolated, uncultured autologous stromal cells (1.5×106 cells/kg) or control solution was injected into the infarct artery. Cardiac function and area at risk were determined by (99m)Tc-SPECT. RESULTS: Eight weeks after infarction, cell treated pigs showed a 20% smaller myocardial perfusion defect compared to control animals (35±9% vs. 44±5% of LV, treated vs. control, respectively, p<0.05). The reduction of the perfusion defect was associated with a significantly higher myocardial salvage index in the cell group as well as a significant increase in ejection fraction compared to control (EF at 8 weeks 43±7% vs. 35±3%, treated vs. control, respectively, p<0.05). This functional improvement was reflected by an increased wall thickness of the infarct and border zone in the treated group (11.2±2.2 mm) compared to control (8.6±1.6 mm, p<0.05) as well as an increased capillary density in the border zone (treated vs. control; 41.6±17.9 vs. 32.9±12.6 capillaries per 0.1 mm², p<0.05). CONCLUSIONS: This study demonstrates for the first time that recovery and intracoronary delivery of uncultured autologous tissue derived stromal cells at time of vessel reperfusion is feasible and improves ventricular function.

[Intercommunication and information flow. An explorative study about ward rounds and patients' documentation]. / Interkommunikation und Informationsweitergabe. Eine explorative Studie zur Visite und Patientendokumentation.

In modern patient interprofessional communication is an impor tant factor of good outcome. The aim of this study was to analyse the intercommunication during ward rounds and information passed by patients' documentation on an internal and geriatric medicine ward. Beside frequent interruptions the ward rounds showed a restricted flow of information that is based and targeted on the chief physician Nursing staff felt excluded from the informational flow. Regarding patients' documentation staff complained about lack of information and illegible notes. Availability of written information was found to be problematic. A team-orientated approach could help to improve interprofessional communication in the future. Besides the importance of carefully performed documentation as a reliable form of communication, communicative contribution of the nursing staff has to be upvalued.

Electrophysiological consequence of adipose-derived stem cell transplantation in infarcted porcine myocardium.

AIMS: Aim of this study was to investigate the effect of intracoronary administration of freshly isolated adipose-derived mononuclear cells (ADMCs) on myocardial vulnerability to arrhythmia induction after infarction. METHODS AND RESULTS: A transmural myocardial infarction in an experimental porcine model was induced by occlusion of the mid-left anterior descending artery with an angioplasty balloon for 3 h. Upon reperfusion, a cellular suspension with freshly isolated ADMCs (1.5 x 10(6) cells/kg BW) or vehicle alone was injected into the infarct artery. All animals underwent a programmed ventricular stimulation at 8 weeks follow-up for possible induction of ventricular arrhythmias using a train of 8 S1 stimuli. Cell injections did not cause acute ventricular arrhythmia, bradycardia, or conduction block. The cycle length of the ventricular arrhythmia was compared at 1 and 10 s following its induction. Despite comparable infarct size in both groups, we found that the cycle length of the induced ventricular arrhythmia in the ADMC-treated group was significantly longer compared with control animals (P < 0.05). We also found that extra-stimuli were required for arrhythmia induction in the ADMC-treated group compared with control animals. CONCLUSION: Freshly isolated autologous stem cell therapy is not proarrhythmic in pigs.

Characterization of 75:25 poly(l-lactide-co-epsilon-caprolactone) thin films for the endoluminal delivery of adipose-derived stem cells to abdominal aortic aneurysms.

Abdominal aortic aneurysms occur in 5-7% of men over the age of 60 and their incidence is rising. Current therapies remove the affected tissue or prevent blood flow through the aneurysm, but do not repair the underlying structural changes of the vascular wall. Adipose tissue derived stem cells (ADSCs) seeded on a biodegradable thin film and delivered endoluminally to the aneurysm site could potentially repair the vessel wall, preventing growth and rupture of the aneurysm. In this study, the mechanical and degradation properties of a novel 75:25 poly(l-lactide-co-epsilon-caprolactone) (PLCL) thin film, as well as, the effects of different surface structures on stem cell adherence and resistance to shear stress was investigated. It was possible to reproducibly create films of consistent physical properties. These films degraded approximately 50% in 6 month, which would be a sufficient time to allow cells to engraft in the aortic wall. Ethylene oxide treatment significantly increased the stiffness and yield stress of the films, which exhibit >700% elongation. Treatment of the films with NaOH and HCl induced the formation of surface texture on the films; however, this texture did not affect stem cell adherence or resistance to delamination by shear stress when compared to nontreated or fibronectin-coated films. These results indicate that PLCL thin films have a sufficient degradation time and mechanical strength to serve as a scaffold in vivo for ADSCs, and that ADSCs seeded on the thin film can withstand a range of physiologic shear stresses.

Correlation between serial measurements of N-terminal pro brain natriuretic peptide and ambulatory cardiac filling pressures in outpatients with chronic heart failure.

BACKGROUND: Serial measurements of N-terminal pro brain natriuretic peptide (NT-proBNP) have been suggested for the management of outpatients with chronic heart failure (CHF). The relationship between NT-proBNP plasma levels and central haemodynamic parameters in this setting is not known. METHODS: In 19 outpatients with CHF, NT-proBNP was related to central haemodynamic information, continuously measured with an implanted haemodynamic monitor (IHM) during 24 h of daily living activities ("24 h") and during supine rest ("rest"). In 13 patients, three to seven serial measurements were obtained with a mean time interval of 39 days (range 19-113). RESULTS: At the first visit (n=19), NT-proBNP plasma levels were dispersed over a wide range of filling pressures and not correlated with the 24 h median of the right ventricular systolic pressure (RVSP) and the estimated pulmonary artery pressure (ePAD). However, in the individual patient, serial measurements yielded significant positive correlations between NT-proBNP and RVSP (p=0.006) and ePAD (p=0.001). During "24 h" compared with "rest", the median RVSP and ePAD were elevated by 20+/-16% and 32+/-18%, respectively, and corresponded better with NT-proBNP (p<0.05). CONCLUSION: In outpatients with CHF, single measurements of NT-proBNP are not correlated with cardiac filling pressures. However, serial measurements of NT-proBNP in each individual patient show a significant positive correlation with central haemodynamic parameters and reflect changes in the haemodynamic state over time.

Partnership for the heart. German-Estonian health project for the treatment of congenital heart defects in Estonia.

Congenital heart defects (CHD) occur in 8 per 1000 live births. If they remain untreated, 70-80% of these patients die in early childhood. With modern diagnostic and treatment procedures, 90% of these patients reach adulthood. Within 8 years following reunification of Germany, it was possible to improve treatment for CHD in former East Germany to West German standards. Based on the experience gained in this process, a plan for improvement of care of Estonian patients with CHD was developed and implemented in the German-Estonian project, "Partnership for the Heart". The main elements of the project were (1) the training of Estonian physicians in Germany, (2) training courses conducted by German and Estonian specialists in Estonia and (3) use of telemedicine for consultation on a continuous basis. During the project 15 Estonian patients underwent cardiac surgery and/or catheter interventions performed by a joint team of German and Estonian specialists. The infant mortality due to CHD in Estonia fell by 28% during the project period. Key techniques of cardiac surgery are now being employed in Estonia without outside support, indicating the success of the training program and the long-term improvements to cardiac health care in Estonia. The total project costs were 314,252 Euro (euro), which is 50% lower than the estimated cost of treating the 15 patients abroad in Western Europe. The structure of "Partnership for the Heart" and the modified self-sufficiency model of medical care have not only produced results for Estonia but can be taken as a template for future bilateral health projects with other transition countries and for other fields of medical specialisation, and thus might aid a European health policy.

Three-dimensional mapping of earliest activation after near-threshold ventricular defibrillation shocks.

INTRODUCTION: Following shocks with a 50% defibrillation success (DFT50) delivered from electrodes at the right ventricular (RV) apex and superior vena cava (SVC), the earliest epicardial postshock activation always appears focally in the left ventricular (LV) apex for both successful and failed shocks. Because the heart is a three-dimensional (3D) structure, questions remain whether this activation truly arises from a focus or the focal pattern represents epicardial breakthrough resulting from intramural reentry. To answer these questions, 3D electrical mapping was performed. METHODS AND RESULTS: In six pigs, 60 to 84 epoxy fiberglass needles (0.7-mm-diameter), each containing six electrodes 2 mm apart, were inserted into the LV with 3- to 5-mm spacing around the apex and 5- to 10-mm spacing near the base. Ten DFT50 shocks (RV-->SVC, biphasic, 6/4 msec) were delivered after 10 seconds of fibrillation in each animal. The first five activations after each shock were mapped. Of 60 DFT50 shocks, 31 were successful, of which the first postshock cycle was a sinus beat in 13. In the other 18 successful shock episodes, the first postshock activation was detected 63 +/- 16 msec after the shock, which was not significantly different from the 58 +/- 23 msec postshock interval for the 29 failed shock episodes. In these 47 successful and failed shock episodes, the earliest postshock activation always arose focally from the LV apex. Its origin was in the subepicardium in 76% +/- 17%, midmyocardium in 16% +/- 12%, and subendocardium in 8% +/- 6% of cases. CONCLUSION: Following near-DFT50 shocks, the first postshock cycles did not arise by macroreentry. Instead, they originated from a true focus or microreentry, most commonly near the epicardium.

Repetitive monomorphic ventricular tachycardia originating from the aortic sinus cusp: electrocardiographic characterization for guiding catheter ablation.

OBJECTIVES: We sought to investigate the electrocardiographic (ECG) characteristics for guiding catheter ablation in patients with repetitive monomorphic ventricular tachycardia (RMVT) originating from the aortic sinus cusp (ASC). BACKGROUND: Repetitive monomorphic ventricular tachycardia can originate from the right ventricular outflow tract (RVOT) and ASC in patients with a left bundle branch block (LBBB) morphology and an inferior axis. METHODS: Activation mapping and ECG analysis was performed in 15 patients with RMVT or ventricular premature contractions. The left main coronary artery (LMCA) was cannulated as a marker and for protection during radiofrequency delivery if RMVT originated from the left coronary ASC. RESULTS: During arrhythmia, the earliest ventricular activation was recorded from the superior septal RVOT in eight patients (group 1) and from the ASC in the remaining seven patients (group 2). The indexes of R-wave duration and R/S-wave amplitude were significantly lower in group 1 than in group 2 (31.8+/-13.5% vs. 58.3+/-12.1% and 14.9+/-9.9% vs. 56.7+/-29.5%, respectively; p < 0.01), despite similar QRS morphology. In five patients from group 2, RMVT originated from the left ASC, with a mean distance of 12.2+/-3.2 mm (range 7.3 to 16.1) below the ostium of the LMCA. In the remaining two patients, the RMVT origin was in the right ASC. All arrhythmias were successfully abolished. None of the patients had recurrence or complications during 9+/-3 months of follow-up. CONCLUSIONS: On the surface ECG, RMVT from the ASC has a QRS morphology similar to that of RVOT arrhythmias. The indexes of R-wave duration and R/S-wave amplitude can be used to differentiate between the two origins. Radiofrequency ablation can be safely performed within the left ASC with a catheter cannulating the LMCA.

Electroanatomic substrate of idiopathic left ventricular tachycardia: unidirectional block and macroreentry within the purkinje network.

BACKGROUND: An abnormal potential (retroPP) from the left posterior Purkinje network has been demonstrated during sinus rhythm (SR) in some patients with idiopathic left ventricular tachycardia (ILVT). We hypothesized that this potential can specifically be identified and be a critical substrate for ILVT. METHODS AND RESULTS: In 9 patients with ILVT and 6 control patients who underwent mapping of the left ventricle during SR using 3-dimensional electroanatomic mapping, an area with retroPP was found within the posterior Purkinje fiber network only in patients with ILVT. The earliest and latest retroPP was 185.4+/-57.4 and 465.2+/-37.3 ms after Purkinje potential; in the other patient with ILVT, an entire left ventricle mapping demonstrated a slow conduction area and passive retrograde activation along the posterior fascicle during ILVT. ILVT was noninducible in 3 patients after SR mapping. Diastolic potentials critical for ILVT during ILVT coincided with the earliest retroPP during SR in 7 patients. Mechanical termination of ILVT occurred in 5 patients. A single radiofrequency pulse was applied at the site with mechanical translation in 5 patients and the site with diastolic potential in 2 patients, and 3 radiofrequency pulses were delivered to the site with the earliest retroPP in the other 3 patients without inducible ILVT after SR mapping. No ILVT was inducible during control stimulation, and none recurred during follow-up of 9.1+/-5.1 months. CONCLUSION: In patients with ILVT, abnormal retroPP within the posterior Purkinje fiber network is a common finding. The earliest retroPP critical for ILVT substrate can be used for guiding successful ablation.