Heart failure following acute myocardial infarction (AMI) is a major cause of morbidity and mortality. Our previous observation that injection of apoptotic peripheral blood mononuclear cell (PBMC) suspensions was able to restore long-term cardiac function in a rat AMI model prompted us to study the effect of soluble factors derived from apoptotic PBMC on ventricular remodelling after AMI. Cell culture supernatants derived from irradiated apoptotic peripheral blood mononuclear cells (APOSEC) were collected and injected as a single dose intravenously after myocardial infarction in an experimental AMI rat model and in a porcine closed chest reperfused AMI model. Magnetic resonance imaging (MRI) and echocardiography were used to quantitate cardiac function. Analysis of soluble factors present in APOSEC was performed by enzyme-linked immunosorbent assay (ELISA) and activation of signalling cascades in human cardiomyocytes by APOSEC in vitro was studied by immunoblot analysis. Intravenous administration of a single dose of APOSEC resulted in a reduction of scar tissue formation in both AMI models. In the porcine reperfused AMI model, APOSEC led to higher values of ejection fraction (57.0 vs. 40.5%, p < 0.01), a better cardiac output (4.0 vs. 2.4 l/min, p < 0.001) and a reduced extent of infarction size (12.6 vs. 6.9%, p < 0.02) as determined by MRI. Exposure of primary human cardiac myocytes with APOSEC in vitro triggered the activation of pro-survival signalling-cascades (AKT, Erk1/2, CREB, c-Jun), increased anti-apoptotic gene products (Bcl-2, BAG1) and protected them from starvation-induced cell death. Intravenous infusion of culture supernatant of apoptotic PBMC attenuates myocardial remodelling in experimental AMI models. This effect is probably due to the activation of pro-survival signalling cascades in the affected cardiomyocytes.Electronic supplementary materialThe online version of this article (doi:10.1007/s00395-011-0224-6) contains supplementary material, which is available to authorized users.
Our results demonstrate that soluble ST2, a marker for Th2 cytokine producing cells, is increased in sepsis and trauma patients, and they provide further evidence for a shift from Th1- to Th2-biased cells.
Despite equal blood loss from chest drains, both colloids interfered with blood coagulation and produced greater haemodilution, which was associated with more transfusion of blood products compared with crystalloid use only.
Our results indicate that the implantation of bioprostheses elicits a specific humoral immune response against alpha-Gal bearing cells compared to controls within 3 months after cardiac surgery. The complete absence of IB4/DAPI positive structures 12 months after implantation indicates a specific degradation of alpha-Gal bearing cells through previous exposure to the human blood circuit.
Age shows a trend toward a higher risk of mortality but does not predict a higher incidence of permanent neurologic injury after ascending aortic and arch repair. As utilization of deep hypothermic circulatory arrest remains the only independent predictor of permanent neurologic injury, alternative approaches to maintain cerebral perfusion during ascending aortic and arch repair are warranted.
As known from patients with pulsatile ventricular assist devices (VADs), early mobilization, physical exercise, and return to normal life are essential for optimal recovery. Recently, implantable rotary pumps became available for extended left ventricular support as bridges to transplantation. Modified procedures are essential for patient training and hospital discharge. The MicroMed-DeBakey VAD was implanted in 10 patients with end-stage heart disease. After recovery, regular ergometer training was performed with loads adapted to the patient's condition. Procedures for patient observation under outdoor conditions and a blood pressure measuring device for low pulse pressure conditions were developed. Improvement of physical condition was achieved in 8 patients. In the first 2 patients, exercise capacity was limited due to flow obstruction. In the following patients, an increase of workload on the ergometer up to 120 W was observed. Correlated with training, lactate/load relationship and heart rate decreased. Three patients were discharged from the hospital during support. The DeBakey-VAD system can support patients for extended time periods and is suitable for recovery and exercise. Under optimal patient and environmental conditions, discharge from the hospital can be obtained.
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