BACKGROUND:40 000 to 60 000 people develop malignant pleural effusion (MPE) in Germany each year. The most common causes are lung cancer and breast cancer. Patients with pleural carcinomatosis have a median survival time of four months.METHODS:We investigated the current health services situation regarding treatment with indwelling pleural catheters (IPC) versus talc pleurodesis (TP) in Germany based on registry data from the Federal Statistical Office, the Pleural Tumor Registry of the German Society for Thoracic Surgery, and the IPC registry of the ewimed GmbH company. In addition, we conducted a selective literature review on IPC and TP.RESULTS:The symptoms of dyspnea and thoracic pressure determine the need for therapy in MPE. Both TP and IPC are effective treatment options for MPE. Both therapeutic procedures are considered equally effective with respect to the relief of dyspnea, post-interventional quality of life, and complication rates. TP yields a higher rate of successful pleurodesis than IPC (relative risk: 1.56; 95% confidence interval: [1.26; 1.92]; p < 0.0001), while patients who receive an IPC stay in the hospital for a shorter time than those who undergo TP (a difference of slightly more than two days). The survival of patients with MPE is not affected by which of the two local therapeutic procedures is chosen.CONCLUSION:The indication for either IPC or TP needs to be determined individually for each patient on the basis of his or her general condition, symptoms, clinical situation ("trapped lung"), and prognosis.

The authors report two cases of stent-assisted embolization (SAE) in the aorta. In one case, SAE was performed for treatment of a pseudoaneurysm; the procedure consisted of stent placement and embolization with an AMPLATZER Vascular Plug and detachable coils through the stent struts. In the second case, SAE was performed to stop acute bleeding from an aortoureteral fistula. Before SAE in this case, the aortic bifurcation was reconstructed with self-expandable and balloon-expandable stents. SAE was technically successful in both cases. SAE for aortic pathologic processes may be useful in selected cases as an alternative to surgery or endovascular stent-graft therapy.

To longitudinally assess the value of cardiac functional and viability imaging as a supplement to MR angiography in patients with atherosclerotic disease.

Objective: Permanent mild-to-severe brain injury with neurologic sequelae remains a significant source of postoperative morbidity in cardiovascular surgery. There is increasing evidence that erythropoietin confers neuroprotective effects in various conditions of neuronal damage, such as hypoxia and cerebral ischaemia. Using a surviving porcine model, this study evaluates whether systemic treatment with erythropoietin induces brain protection in deep hypothermic circulatory arrest (DHCA). Methods: Sixteen pigs (42 +/- 3 kg) randomly assigned into two groups (n = 8) were subjected to 60 min of DHCA at an intracerebral temperature of 20 degrees C. The animals of the erythropietin group were treated perioperatively with 500 IU kg(-1) of recombinant human erythropoietin on 3 consecutive days beginning the day before surgery. Intracerebral monitoring was performed by subcortical microdialysis, brain tissue oxygenation, measurement of brain temperature and intracranial pressure. Neurologic recovery was evaluated daily. Perioperative S100 beta protein serum level was determined. The brains were harvested on the postoperative day 6 after perfusion fixation. Multiple brain regions were investigated histologically for hypoxic-ischaemic damage. Results: The subcortical brain microdialysis detected significant increase of glycerol and lactate concentrations in both groups (P = 0.0001) with considerably higher concentrations in the brain of control animals (P = 0.011). There were no significant differences in neurological outcome (P = 0.15). Erythropoietin-treated animals tended to a more complete and rapid neurological recovery. By contrast, none of the animals in the control group achieved complete neurological recovery. S100 beta protein as a putative marker of cerebral injury tended to be higher in the control group. Brain infarction was detectable in all control animals but only in two erythropoietin-treated animals. Conclusion: These results suggest some beneficial neuroprotective effects of erythropoietin in this model of global brain ischaemia induced by 1 h of hypothermic circulatory arrest. (C) 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Background: One of the cell sources valuable for cardiac stem cell therapy is endothelial progenitor cells (EPCs) because of their favourable properties These cells may contribute to neoangiogenesis and regenerate infarcted myocardium In the previous study, a rapid and efficient method was established for direct isolation of EPCs from porcine bone marrow Aim: To examine the influence of aptamer-isolated EPCs in vivo on vascularization and cardiac function Material and methods: Immediately after obtaining bone marrow or peripheral blood from healthy pigs endothelial progenitor cells were isolated The EPCs were incubated with Dynabeads (R), which were coated either with aptamer or CD 31 antibodies. Subsequently myocardial ischaemia was induced and then the groups were treated with either aptamer-isolated EPCs or antibody-isolated EPCs LVEF was quantified by echocardiography After four weeks, histological examinations were assessed Results: The group receiving aptamer-isolated EPCs demonstrated significantly more large-sized capillaries than the other groups (p <= 0 05) Four weeks after myocardial infarction, the change in LVEF did not show any significance within or between all four groups Conclusions: Our results showed that transplantation of aptamer-isolated EPCs after myocardial infarction improves angiogenesis This new therapeutic method may bring greater efficacy of cellular cardiomyoplasty after myocardial infarction.

Rationale and Objectives: The long-term prospects for patients with peripheral-arterial-occlusive disease (PAOD) must be considered in the context of coexistent generalized atherosclerosis. We sought to determine the added clinical information of noninvasive magnetic resonance imaging (MRI) for detecting asymptomatic atherosclerotic disease in patients already at high risk.Materials and Methods: Eighty-four patients (64 men, mean age 66.2 +/- 10.0 years, range 34-84 years) with suspected or known PAOD were examined using a comprehensive cardiovascular MRI protocol. Two experienced observers reviewed all MRIs for the presence of "relevant findings," which were defined as pathology requiring immediate therapy or mid-term follow-up.Results: Assessment of cardiac structures and function in 84 study patients yielded new pathology in 40 (48%) patients, whereas cerebral imaging revealed new findings in 45 (54%) patients. Previously unsuspected vascular findings were evident in 46 (55%) patients. Using the information from the MRIs, in 54 (64%) of patients mid-term follow-up was required, whereas in 7 (8%) patients a change of therapy or immediate treatment was necessary.Conclusion: Whole-body cardiovascular MRI is able to detect symptomatic and unsuspected findings in patients with PAOD. This technique was able to detect several vascular abnormalities that necessitated immediate medical attention and intervention in patients already identified as high-risk patients and, therefore, may show an increasing impact to determine individual therapeutic and follow-up concepts.

The outcome of patients after coronary bypass grafting is greatly influenced by the type of graft material employed, especially regarding the rate of graft restenosis. Besides direct thrombotic events, the leukocyte-endothelial interaction modulated by adhesion molecules is identified to be the central cause leading to graft alterations. This study deals with a new therapeutic concept in order to achieve superior protection of a new bypass graft by blocking the adhesion molecule expression pathway with RNA interference to inhibit the initial leukocyte adhesion and transmigration. Leukocyte binding to adhesion molecules on activated human venous endothelial cells (HVECs) was determined by video-assisted microscopy in a flow chamber mimicking physiological conditions. The cells under study were sequentially transfected in a nonviral manner with specific short interfering RNA-sequences (siRNA) targeting E-selectin, intercellular adhesion molecule, and vascular adhesion molecule. After stimulation of adhesion molecule expression by tumor necrosis factor, a leukocyte-rich suspension was run through the chamber and the attaching leukocytes were counted. Transfection with specific siRNA targeting three different adhesion molecules resulted in a highly significant reduction of leukocyte attachment to activated HVECs in each case compared to the controls (p < 0.05). Transfection with a mixture out of all three siRNA-sequences showed the lowest leukocyte adhesion (p < 0.05) compared to the controls. siRNA-sequences inhibit the adhesion molecule expression on HVECs in an extremely effective way; not only in a single transfection of specific molecules but also in a parallel transfection of multiple sequences in one transfection. Accordingly, siRNA treatment significantly reduced adhesion of leukocyte cells to HVECs compared to controls. This study showed for the first time an effective knockdown of the leukocyte-endothelium interactions by transfection of HVECs with a cocktail consisting of three highly specific siRNAs against three different endothelial adhesion molecules.

To assess renal artery stenosis (RAS) by 3D phase contrast (PC) MR angiography and dynamic perfusion imaging of the kidneys.On a standard 1.0 T MR imaging system (Magnetom Expert, Siemens), 32 patients with angiographically proven unilateral RAS were examined using a 3D PC sequence (TR 40 ms/TE 9 ms/venc 30 cm/s). An ECG-gated Turbo-FLASH 2D sequence (TR 4.5 ms/TE 2.2 ms/TIeff. 400 ms) was applied to study the first pass of paramagnetic contrast agent (0.1 mmol Gd-DTPA/kg) through the kidneys. Signal intensity (SI) over time curves of the renal cortex were obtained and evaluated considering temporal relation and percentage of maximum SI compared to the aorta and normal kidneys. Analysis of the MRA was performed by two independent blinded readers. The gold-standard DSA was interpreted by consensus reading of two experienced radiologists.RAS was detected by 3D PC MRA with a sensitivity of 93% and specificity of 81% (ppv 82%, npv 93%, accuracy 87%, kappa = 0.61). Maximum SI in RAS was significantly decreased (p < 0.001-0.0001). A temporally delayed enhancement of 1.5 +/- 1.3 s was found for RAS > 75% (p < 0.002) but not for RAS < 75% (p > 0.1).3D PC MRA is capable of detecting RAS in a high percentage of patients. Dynamic perfusion imaging of the kidneys, applied additionally, can confirm the diagnosis and give valuable information about the hemodynamic relevance of RAS in suspected unilateral disease.

Ziel: Validierung von MR-Methoden zur Bestimmung von Funktionsparametern des linken Ventrikels (LV) an Probanden und Patienten mit Aortenvitien. Material und Methoden: Bei 1,5 T erfolgte die Untersuchung von 20 gesunden Probanden, 15 Patienten mit Aortenstenose (Aost.) sowie prä- und postoperativ von 7 Patienten mit Aorteninsuffizienz (AI). Bestimmt wurden Funktions- und Zeitparameter des LV (Ejektionsfraktion, -volumen/Zeit, maximaler Fluß in der Aorta und Zeitintervall bis zu diesem) mittels Phasenkontrastmethode (FLASH 2D, TR 24 ms, TE 5 ms, venc 250 cm/s) und volumetrischen Berechnungen aus Cine-Studien in Atemanhaltetechnik (segmentierte FLASH 2D, TR 100 ms, TE 4,8 ms, Flipwinkel 25°). Goldstandard waren invasive Messungen nach Fickschem Prinzip. Intra- und Interbeobachter-Variabilität wurden an Untersuchungen von Probanden festgelegt. Ergebnisse: Die Patienten mit Aortenvitium wiesen gegenüber Probanden deutlich veränderte Funktions- und Zeitparameter des LV auf (p < 0,0001). Bei postoperativen Untersuchungen war bei AI eine Regredienz auf Grad < 1° nachweisbar (p = 0,03). Bestimmungen des Herzzeitvolumens mittels Flußmessungen korrelierten besser mit dem Goldstandard (r = 0,66, p = 0,0007) als volumetrische Messungen (r = 0,47, p = 0,02). Die Interbeobachter-Variabilität lag bei 2,5 + 2,7 %/4,5 + 6,9 % (Flußmessung/Volumetrie), die Intrabeobachter-Variabilität betrug 1,7 + 1,6 %/ 3,3 + 2,2 %. Schlußfolgerung: MR-tomographische Bestimmungen funktioneller Parameter des LV sind mit der Flußmessung sehr zuverlässig durchführbar und Unterschiede zwischen gesunden Probanden und Patienten können sicher erkannt werden. Das Verfahren erlaubt Verlaufskontrollen in der klinischen Routine.

Objectives: Transendothelial migration of leukocytes mediated by adhesion molecules promotes venous bypass failure by increasing neointimal thickening and rapid progressive atherosclerosis. The discovery of short interfering RNA (siRNA) opens new perspectives towards non-viral silencing of adhesion molecules on the vascular wall of venous bypass grafts. This study deals with the power of siRNA to transiently block leukocyte-endothelial interactions in a dynamic flow model in order to prevent leukocyte migration in an early stage.

We report a 67-yr-old male after multiple surgical procedures for treatment of arterial occlusive disease who suffered an anaphylactic reaction after administration of aprotinin (Trasylol) prior to urgent coronary artery bypass surgery. The patient had been treated with aprotinin-containing fibrin sealant in 2004 and in 2007, 2 wk before coronary artery bypass surgery. The postoperative serologic screening revealed positive results for qualitative aprotinin-specific IgG, highly elevated quantitative aprotinin-specific IgG and moderately elevated aprotinin-specific IgE antibodies.

Objective: Due to their insufficient biocompatibility and high thrombogenicity, small diameter artificial vascular prostheses still do not show a satisfactory patency rate. In vitro endothelialization of artificial grafts before implantation has been established experimentally years ago, but, has never been used for routine clinical applications. This study deals with the coating of graft surfaces with capture molecules for circulating endothelial progenitor cells (EPCs), mimicking a pro-homing substrate to fish out EPCs from the bloodstream after implantation.

Aims: The incidence of anaphylactic reaction (AR) to aprotinin is rising. The risk of AR to aprotinin after reexposure is time dependent. Most reported AR occured between 2 and 12 weeks after first exposure. Previous studies examined the immunological response within focus on the first 6 months; however, no study has been focused on antibody formation within the first week. The aim of this study was to investigate aprotinin specific antibody formation – a major risk factor for AR – during the first eight days post exposure.

Purpose: The aim of the study was to assess the feasibility and additional diagnostic information of cardiac MRI as a supplement to state-of-the-art MR angiography (MRA) in the case of vascular risk patients. Therefore, the prevalence of delayed myocardial enhancement (DE) was determined in patients suffering from peripheral artery disease (PAD) and a clinical follow-up was evaluated after 2 years.Materials and Method: 87 consecutive patients (ages 66 10 years, 67 males) with symptomatic peripheral arterial occlusive disease (n=68) or abdominal aortic aneurysm (n=19) were examined using delayed cardiac enhancement (DE) within the clinical indication of MRA at a 1.5T system. A follow-up examination was carried out two years later (24 months 4 months) with regards to cardiac events (cardiac death, myocardial infarction or acute coronary syndrome, heart insufficiency, coronary revascularization).Results: In total, 40/87 patients had myocardial infarctions shown in MRI (46%). In 25 patients (29%), the myocardial infarction was already known, while in 15 patients (17%) an occult progressing infarction was diagnosed (38% of the myocardial infarcts). Follow-up data was able to be obtained after 2 years for 82 patients. 15 patients had a major cardiac event during the follow-up period, and 10 (67%) of them already showed DE in the MRI. In the group with occult progressing infarctions, cardiac events occurred in 40% (6/15 patients, cardiac death n=1, ischemia n=4, heart insufficiency n=1, bypass n=1), in patients with known infarction in 17% (4/23 patients, cardiac death n=1, ischemia n=3, bypass n=2) and in 11% of patients without myocardial scars (5/44 patients, cardiac death n=1, ischemia n=2, heart insufficiency n=2).Conclusion: Cardiac MRI in combination with MRA was feasible and showed a high prevalence of known and unexpected myocardial infarctions. This was of prognostic relevance in the follow-up 2 years later. Therefore, this enables important additional information regarding to the risk stratification and eventually targeted therapy in risk patients with PAD.

Objective: To assess myocardial viability in acute and subacute infarcts using different multislice spiral computed tomography contrast protocols with magnetic resonance imaging (MRI) correlation. Methods: Seven pigs were studied with 64-multislice spiral computed tomography and MRI (1.5 T) at a median of 1 and 21 days after temporary occlusion of the second diagonal branch. Computed tomography was performed at 3, 5, 10, and 15 minutes after injection of contrast medium. Contrast agent was applied either as a bolus (protocol 1; n = 7 for the first; n = 5 for the second scan) or as a bolus plus 30 mL of subsequent 0.1 mL/s low-flow (protocol 2; n = 7 for the first; n = 6 for the second scan). Finally, histological sections were obtained. Volumes of infarcted myocardium were assessed as the percentage of the left ventricle. Computed tomography attenuation values were obtained, and image quality was assessed. Results: When compared with protocol 1, protocol 2 provided greater Hounsfield unit attenuation difference between viable and nonviable myocardium at 5, 10, and 15 minutes (P = 0.19; 0.003; 0.0006) and an additional significant contrast between nonviable myocardium and ventricular blood at 3 and 5 minutes (P < 0.001). Image quality was rated significantly higher with the use of protocol 2 at 5, 10, and 15 minutes (P ≤ 0.027) and for all time points use of protocol 2 resulted in improved correlation of acute and subacute infarct size with MRI. Conclusions: Good correlation of infarct zones with MRI was achieved for both acute and subacute infarcts. With the use of a bolus/low-flow protocol, image quality was substantially improved by means of a higher tissue contrast.

Isolation of huge quantities of primary cells from whole organs like the heart becomes increasingly important, especially for the emerging research field of tissue engineering and regenerative medicine. This study deals with the isolation of pig cardiomyocytes, in contrast to the standard mouse or rat models, because we aimed to draw attention to the species, which are genetically more closely related to the human organism. The bigger operative and veterinary expenditure of the pig-heart model can only be justified by a technique that supplies a big amount of qualitative high-grade cardiomyocytes. In our model, the quality is guaranteed by protection of the heart, already in situ, by a cardioplegia and a careful application of collagenase to soften the tissue. The construction of a new apparatus which includes enormous costs was not necessary, since the perfusion equipment was realized from two commercially available HLMsets, which were modified and connected to each other. Our model makes it possible to rinse the whole myocardium, which leads to a better output than models that only prepare a part of the myocardium around a coronary artery. The careful harvesting of high-grade cardiomyocytes is an important source of successful cell cultures to be used for numerous experimental applications, may reduce animal experiments and, additionally, represents a chance for perfusionists to become an important partner in interdisciplinary research projects. Perfusion (2007) 22, 137—142.

Objective: Expression of adhesion molecule receptors on venous endothelial cells crucially influences the fate of venous grafts by mediating leukocyte-endothelium interactions. These interactions include adhesion of leukocytes to the endothelium, followed by transendothelial migration, leading to neointimal hyperplasia (NIH) and finally graft occlusion. Therefore, inhibition of adhesion molecule expression may be a promising strategy to improve the quality of venous grafts. We tested the efficiency of non-viral transfection of human venous endothelial cells (HVEC) with short interfering RNA (siRNA) to specifically down-regulate adhesion molecule expression.Methods: Primary cultures of HVEC were examined for expression of the adhesion molecules ICAM1, VCAM1 and E-selectin (SELE) after non viral siRNA transfection. Adhesion molecule expression was measured by flow cytometry, real-time polymerase chain reaction and immunoblotting after stimulation with TNF-alpha, an inflammatory cytokine.Results: Non-transfected cells showed a strong increase of adhesion molecule expression following cytokine stimulation (P < 0.01). Upon transfection with specific siRNAs a sixfold decrease in ICAM1 (P < 0.001) and SELE expression and cell positivity (P < 0.05) and a twofold decrease in VCAM 1 expression and cell positivity (P < 0.01) Pcould be observed. SiRNA-mediated gene suppression of adhesion molecules was also reflected by corresponding decreases in adhesion protein and transcript levels.Conclusions: The expression of adhesion molecules on HVECs can be effectively inhibited by specific siRNAs using a safe, non-viral transfection approach. This is a promising tool to pre-condition venous bypass grafts in order to interfere with endothelium-leukocyte interactions and to prohibit neointima thickening or atherosclerosis, which are regarded to be the most important causes of venous graft failure.