Enhanced mobilization of the bone marrow-derived circulating progenitor cells by intracoronary freshly isolated bone marrow cells transplantation in patients with acute myocardial infarction.

Autologous bone marrow cell transplantation (BMCs-Tx) is a promising novel option for treatment of cardiovascular disease. We analysed in a randomized controlled study the influence of the intracoronary autologous freshly isolated BMCs-Tx on the mobilization of bone marrow-derived circulating progenitor cells (BM-CPCs) in patients with acute myocardial infarction (AMI). Sixty-two patients with AMI were randomized to either freshly isolated BMCs-Tx or to a control group without cell therapy. Peripheral blood (PB) concentrations of CD34/45(+) - and CD133/45(+)-circulating progenitor cells were measured by flow cytometry in 42 AMI patients with cell therapy as well as in 20 AMI patients without cell therapy as a control group on days 1, 3, 5, 7, 8 and 3, 6 as well as 12 months after AMI. Global ejection fraction (EF) and the size of infarct area were determined by left ventriculography. We observed in patients with freshly isolated BMCs-Tx at 3 and 12 months follow up a significant reduction of infarct size and increase of global EF as well as infarct wall movement velocity. The mobilization of CD34/45(+) and CD133/45(+) BM-CPCs significantly increased with a peak on day 7 as compared to baseline after AMI in both groups (CD34/45(+): P < 0.001, CD133/45(+): P < 0.001). Moreover, this significant mobilization of BM-CPCs existed 3, 6 and 12 months after cell therapy compared to day 1 after AMI. In control group, there were no significant differences of CD34/45(+) and CD133/45(+) BM-CPCs mobilization between day 1 and 3, 6 and 12 months after AMI. Intracoronary transplantation of autologous freshly isolated BMCs by use of point of care system in patients with AMI may enhance and prolong the mobilization of CD34/45(+) and CD133/45(+) BM-CPCs in PB and this might increase the regenerative potency after AMI.

Improved functional activity of bone marrow derived circulating progenitor cells after intra coronary freshly isolated bone marrow cells transplantation in patients with ischemic heart disease.

OBJECTIVES: There is growing evidence that intracoronary autologous bone marrow cells transplantation (BMCs-Tx) in patients with chronic myocardial infarction beneficially affects postinfarction remodelling. In this randomized controlled study we analyzed the influence of intracoronary autologous freshly isolated bone marrow cells transplantation by use of point of care system on cardiac function and on the functional activity of bone marrow derived circulating progenitor cells (BM-CPCs) in patients with ischemic heart disease (IHD). METHODS: 56 patients with IHD were randomized to either received freshly isolated BMC-Tx or a control group that did not receive cell therapy. The functional activity of BM-CPCs in peripheral blood (PB) was measured by migration assay and colony forming unit assay pre- and 3, 6 as well as 12 months after procedure. Global ejection fraction (EF) and infarct size area were determined by left ventriculography. RESULTS: Intracoronary transplantation of autologous freshly isolated BMCs led to a significant reduction of infarct size and an increase of global EF as well as infarct wall movement velocity after 3 and 12 months follow-up compared to control group. The colony-forming capacity of BM-CPCs significantly increased 3, 6 and 12 months after cell therapy compared to pre BMCs-Tx and control group (CFU-E: p < 0.001, CFU-GM: p < 0.001). Likewise, we found significant increase of migratory response to stromal cell-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF) after cell therapy compared to pre BMCs-Tx (SDF-1: p < 0.001, VEGF: p < 0.001) and to control (SDF-1: p < 0.001, VEGF: p < 0.001). There was no significant difference of migratory- and colony forming capacity between pre- and 3, 6, 12 months after coronary angiography in control group without cell therapy. CONCLUSIONS: Intracoronary transplantation of autologous freshly isolated BMCs by use of point of care system may lead to improvement of BM-CPCs functional activity in peripheral blood, which might increase the regenerative potency in patients with IHD.

Cardiac manifestation of the hypereosinophilic syndrome: new insights.

Cardiac manifestation is the major cause of morbidity in patients with hypereosinophilic syndrome (HES). Clinical features range from heart failure to arterial embolism, which are caused by thickening of the endocardium and mural left ventricular thrombosis. Modern magnetic resonance imaging and echocardiography are able to detect fibrosis, eosinophilic infiltrate and thrombi to stage the fibrotic evolution of the disease. Treatment of HES involves standard medication for heart failure, anticoagulant therapy, immunosuppressive therapy and potentially surgical resection. The outcome of HES depends on both the progression of endocardial fibrosis and associated complications and the 5-year mortality is estimated at 30%.

[Regenerative therapy in cardiology]. / Regenerative Medizin in der Kardiologie.

The aim of regenerative medicine is the reconstitution of the physiological structure of critically damaged organs. Bone marrow derived stem cells (BMDCs) show promising therapeutic potential. BMDCs are already used in oncology and are ideally suited for regenerative medicine due to their regenerative potential and safety profile. A variety of cells have been contemplated in cardiology, and there is emerging preclinical and clinical data on the feasibility and safety of different cell lines in the setting of acute myocardial infarction and chronic heart failure. In this review, the various concepts and cells will be discussed in further detail.

[The "broken heart" syndrome--a rare clinical phenomenon]. / Das "Broken Heart"-Syndrom--Ein seltenes klinisches Phänomen.

BACKGROUND AND OBJECTIVE: A clinical entity that mimics acute coronary syndrome with reversible left ventricular systolic dysfunction and is triggered by emotional stress was identified in 6 patients by screening a database of > 1000 patients with the ICD-10 coding of acute coronary syndrome. The search criteria were acute coronary syndrome, normal coronary anatomy, absence of coronary lesions and transient left ventricular dysfunction, triggered by emotional stress. PATIENTS AND METHODS: We analyzed 6 patients, who fulfilled the criteria of (1) acute substernal chest pain with ST-segment elevation and/or T-wave inversion; (2) absence of significant coronary arterial narrowing on angiography, (3) systolic dysfunction with abnormal regional wall motion ("apical ballooning") in the context of (4) severe psychological stress immediately before and triggering the cardiac events. RESULTS: The primary diagnosis for all 6 acutely ill patients accorded with the ICD-code of acute coronary syndrome. All patients had survived and eventually recovered with an LV ejection fraction of 60 +/- 5 %; P = 0.03 and had had recovered normal levels of physical activity at hospital discharge. Of note is the number of women of postmenopausal age. CONCLUSIONS: A transient cardiomyopathy triggered by major emotional stress may mimic an acute coronary syndrome but without significant coronary artery disease. This condition is characterized by reversible cardiac dysfunction and may be more frequent in women. It has a favorable clinical outcome.

[The diagnostic dilemma of acute thoracic pain]. / Das diagnostische Dilemma des akuten Thoraxschmerzes.

Acute aortic dissection is gaining recognition in Western societies, and is being diagnosed with increasing frequency. New diagnostic imaging modalities, longer life expectancy in general, as well as the increase in the number of hypertension patients have all contributed to the growing awareness of aortic dissections. Compared with acute coronary syndrome and lung embolism, aortic dissection is among the most frequently diagnosed life-threatening conditions involving chest pain. Here we report the case of a 59 year old patient suffering from hypertension and discuss the latest diagnostic and therapeutic procedures in the setting of acute chest pain.

[Hematothorax after sudden chest pain]. / Hämatothorax nach plötzlichem Brustkorbschmerz.

HISTORY: A 75-year-old woman was admitted to hospital because of the sudden onset of acute chest pain and dyspnea after defecation. INVESTIGATIONS: The initial working diagnosis was pulmonary embolism because of the clinical findings, laboratory results of elevated fibrin breakdown products and abnormal lung scintigraphy. However, persistent hemorrhagic pleural effusion on contrast enhanced computed tomography and magnetic resonance imaging subsequently revealed imminent rupture of the aorta from penetrating ulceration of the aorta with surrounding intramural hematoma. TREATMENT AND COURSE: Immediate implantation of an aortic stent-graft stopped leakage from the aorta and stabilized the patient's hemodynamic state. At follow up three months later the patient was without thoracic or cardiac symptoms. CONCLUSION: After exclusion of an acute coronary syndrome computed tomography imaging should always be performed in case of acute chest pain with no established cause. Interventional stent-graft placement can be an efficacious treatment option for emergency repair of imminent rupture in the descending aorta.

[Paraplegia after acute thoracic pain]. / Paraplegie nach akutem Thoraxschmerz.

Severe neurological complications such as spinal cord ischemia and paraplegia can occur with acute aortic dissection in 3%. This report describes the case of a 67-year old patient with delayed onset of paraplegia 8 h after acute chest pain. Contrast enhanced computed tomography documented Stanford type B dissection confined to a short segment of the aorta. Furthermore, magnetic resonance imaging revealed intraspinal intraaxial hematoma of the myelon, which can explain the neurological complication. This case shows that even in the scenario of acute aortic dissection other mechanisms for paraplegia may be operational than dissection itself. Paraplegia in this case results from intramyelon bleeding preceding aortic dissection.

Use of human preconditioned phagocytes for extracorporeal immune support: introduction of a concept.

Neutrophils are critical effector cells in humoral and innate immunity and play a vital role in phagocytosis and bacterial killing. If they and/or their specific functions are lacking, then immunoparalysis may occur, and severe diseases like systemic inflammatory response syndrome (SIRS) or sepsis can take a fatal course. In this paper, we discuss the possibility of using preconditioned cells in an extracorporeal biohybrid immune support system. A human promyelocytic cell line was stimulated for different times with all-trans retinoic acid. The resulting cells displayed major signs and functions of mature neutrophilic granulocytes including oxygen radical production, phagocytosis of living and dead Escherichia coli, Staphylococcus aureus, Candida albicans, intracellular killing, and interleukin production. The cells can be expanded to yield a sufficient cell mass, and subsequent prestimulation results in an expression of specific neutrophil functions. Extracorporeal bioreactor experiments seem to be feasible to test the benefit in immunoparalysis-associated diseases like SIRS or sepsis.