Pulsed perfusion in a venous human organ culture model with a Windkessel function (pulsed perfusion venous HOC-model).

BACKGROUND: The effectiveness of human saphenous vein grafting is limited by hyperplasia of the vessel wall. The current paper reports on a pulsed perfused venous human organ culture model (pp-venous HOC-model) with a Windkessel function. MATERIAL/METHODS: Saphenous vein grafts from 21 patients undergoing coronary bypass grafting were cultured either in venous or arterial hemodynamic conditions. Up to four vein segments were fixed in parallel connection and attached to a closed loop pulsed perfusion system consisting of large and small elastic tubes, mimicking the Windkessel function. RESULTS: First, after exposure to arterial blood pressure first signs of reactive cell proliferation (n.s.) were detected at day 4. Second, media thickness of the venous segments in the pulsed pressure group was decreased at day 4 (n.s.) and day 7 (n.s.). Third, staining against smooth muscle alpha actin and v. Willebrand factor was always positive at day 1, 4, and 7. CONCLUSIONS: Pulsed perfusion in a human venous organ culture model with a Windkessel function is an approach to better understand the events taking place during early arterial-vein grafting. First signs of reactive cell proliferation were detected at day four. A period of seven days as described in the current model is probably too short to detect reactive cell proliferation and medial thickening. If the device might be activated for a longer period of time, it should be a suitable model to characterize the effects of intra- and extravascular drug administration as treatment strategies of vein graft disease.

A 25-year-old woman with a gastric GIST and a PET-positive epicardial tumor.

BACKGROUND: A 25-year-old woman presented with a history of abdominal pain. Endoscopy of the upper gastrointestinal tract revealed a tumor that protruded into the prepyloric antrum. After resection, a 'high-risk' gastrointestinal stromal tumor was histologically confirmed. INVESTIGATIONS: Endoscopy, endoscopic ultrasound, hemigastrectomy, [(18)F]-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT scan, histological examination, immunohistochemistry, cardiac MRI, high-resolution CT with electrocardiogram gating, CT angiography, and cardiac surgery. DIAGNOSIS: Gastrointestinal stromal tumor, epicardial paraganglioma, and Carney's syndrome. MANAGEMENT: Abdominal ultrasound and endoscopy combined with endoscopic ultrasound, annual FDG-PET/CT scan.

Edge restenosis: impact of low dose irradiation on cell proliferation and ICAM-1 expression.

BACKGROUND: Low dose irradiation (LDI) of uninjured segments is the consequence of the suggestion of many authors to extend the irradiation area in vascular brachytherapy to minimize the edge effect. Atherosclerosis is a general disease and the uninjured segment close to the intervention area is often atherosclerotic as well, consisting of neointimal smooth muscle cells (SMC) and quiescent monocytes (MC). The current study imitates this complex situation in vitro and investigates the effect of LDI on proliferation of SMC and expression of intercellular adhesion molecule-1 (ICAM-1) in MC. METHODS: Plaque tissue from advanced primary stenosing lesions of human coronary arteries (9 patients, age: 61 +/- 7 years) was extracted by local or extensive thrombendarterectomy. SMC were isolated and identified by positive reaction with smooth muscle alpha-actin. MC were isolated from buffy coat leukocytes using the MACS cell isolation kit. For identification of MC flow-cytometry analysis of FITC-conjugated CD68 and CD14 (FACScan) was applied. SMC and MC were irradiated using megavoltage photon irradiation (CLINAC2300 C/D, VARIAN, USA) of 6 mV at a focus-surface distance of 100 cm and a dose rate of 6 Gy min-1 with single doses of 1 Gy, 4 Gy, and 10 Gy. The effect on proliferation of SMC was analysed at day 10, 15, and 20. Secondly, total RNA of MC was isolated 1 h, 2 h, 3 h, and 4 h after irradiation and 5 microg of RNA was used in standard Northern blot analysis with ICAM-1 cDNA-probes. RESULTS: Both inhibitory and stimulatory effects were detected after irradiation of SMC with a dose of 1 Gy. At day 10 and 15 a significant antiproliferative effect was found; at day 20 after irradiation cell proliferation was significantly stimulated. Irradiation with 4 Gy and 10 Gy caused dose dependent inhibitory effects at day 10, 15, and 20. Expression of ICAM-1 in human MC was neihter inhibited nor stimulated by LDI. CONCLUSION: Thus, the stimulatory effect of LDI on SMC proliferation at day 20 days after irradiation may be the in vitro equivalent of a beginning edge effect. Extending the irradiation area in vascular brachytherapy in vivo may therefore merely postpone and not inhibit the edge effect. The data do not indicate that expression of ICAM-1 in quiescent MC is involved in the process.

Triple-coated stents (Hirudin/Iloprost/Paclitaxel): an in vitro approach for characterizing the antiproliferative potential of each individual compound.

BACKGROUND: Hirudin (H)/iloprost (I)/paclitaxel (P)-coated stents represent a multifactorial approach to reducing the proliferative response caused by ballooning and stenting. The study presented compares the net effect of each individual compound of HIP-coated stents with the summed effect of the compounds in the stent coating. METHODS AND RESULTS: For proliferation prescreening studies, human coronary smooth muscle cells were incubated with H (0.005-500 microg/ml), I (0.00001-1 microg/ml), and P (0.0001-10 microg/ml). After 5 days, cell number was studied in a cell analyzer system. Secondly, 8-mm stents were coated with (1) HI, (2) HIP-10 microg/20 microg/40 microg (HIP5%/10%/20%), (3) P-40 microg (P), (4) IP-40 microg (IP), and (5) HP-40 microg (HP). After 5 days, the effect on cell proliferation and cytoskeletal structures was studied. No antiproliferative effect was found after incubation with H; significant inhibition was seen after incubation with I (p<0.05) or lipophilically dissolved P (p<0.001). After 5 days incubation with HIP5%-, HIP10%-, HIP20%-, P20%-, IP20%-, and HP20%-coated stents, cell proliferation was inhibited by 55.5% (p<0.05), 61% (p<0.05), 57.9% (p<0.05), 59.5% (p<0.001), 59.8% (p<0.001), and 63.3% (p<0.001), respectively. HI- and HIP-coated stents caused a severe destruction of the cytoskeletal structures smooth muscle alpha-actin and alpha-tubulin; despite the destruction, vital cells could be identified with positive FDA staining. CONCLUSIONS: Although both lipophilically dissolved P and hydrophilically dissolved I contributed to the antiproliferative effect, no additive effect of the two compounds was detected. In vivo P can be released more easily from the coating material due to the permanent lipophilic contact of the stent struts with the vessel wall. The current study is the first report on a clear and uncomplicated technique to obtain information on the antiproliferative potential of coated stents before large experimental studies are initiated.

Overexpression of heat shock protein 60/10 in myocardium of patients with chronic atrial fibrillation.

BACKGROUND: Cardiomyocytes respond to chronic atrial fibrillation with increased expression of heat shock protein 60 (HSP60). The aim of this study was to investigate whether expression of the coprotein HSP10 is also increased. METHODS: Right atrial samples from 16 patients undergoing elective cardiac operation were excised and immediately frozen in liquid nitrogen. Eight patients had chronic atrial fibrillation and 8 patients were in sinus rhythm. The HSP60 and HSP10 protein levels were determined by SDS-PAGE, Western blot, and quantified by optical densitometry according to the immunoreactive bands of actin. RESULTS: In myocardial samples from patients with chronic atrial fibrillation we found simultaneous upregulation of both stress proteins. HSP60 expression was more than 2.3-fold and HSP10 expression was more than 2.4-fold increased in atrial myocardium of patients with chronic atrial fibrillation. CONCLUSIONS: These results indicate functional upregulation of mitochondrial HSP60 and HSP10 in response to chronic atrial fibrillation.

Minimally invasive heart valve surgery: already established in clinical routine?

Cardiac valve replacement with the need for open heart surgery still has the highest morbidity and mortality rates among routine cardiac surgery, with the exception of aortic aneurysm repair and surgery for congenital heart defects. Reducing invasiveness is a desirable goal, and different strategies and approaches have been used to achieve this with valve repair or replacement less invasive. Despite the good results reported with minimally invasive techniques, time on extracorporal circulation is always longer compared with the conventional procedures. Since these techniques do not reduce real invasiveness but rather improve the cosmetic results, minimal-access surgery would be a better nomenclature. With the exception of patients at a high risk for sternal infections or redo heart operations, a reduction in postoperative morbidity by the avoidance of a median sternotomy is not yet definitely proven. Meanwhile, most surgeons comply with the demand for minimally invasive surgery posed by patients by reducing the length of the incision in aortic valve replacement and by using a right anterolateral approach with a limited incision for mitral valve operations. However, the use of endoscopic or robotic devices is limited to a few centers, and has not yet found its way into clinical routine. Nonetheless, minimally invasive or minimal-access surgery is now established in many centers, and patients should always be informed of these techniques. When this information is provided objectively and patient selection is carried out accurately, these alternative approaches can help to improve postoperative convalescence.

Enteral application of an immunoglobulin-enriched colostrum milk preparation for reducing endotoxin translocation and acute phase response in patients undergoing coronary bypass surgery--a randomized placebo-controlled pilot trial.

OBJECTIVE: To evaluate the influence of enteral application of an immunoglobulin enriched bovine milk preparation on endotoxin plasma levels, endotoxin neutralizing capacity of plasma (ENC) and the acute phase response (IL-6, CRP) during and after cardiac surgery, in a pilot study. DESIGN, PATIENTS AND METHODS: 60 patients who underwent coronary bypass operations, were evenly enrolled in a placebo-controlled randomized study. The patients were treated by enteral application of either 42 g of a bovine colostrum milk preparation per day or placebo, for 2 days preoperatively. Endotoxin and ENC were sequentially determined intra- and postoperatively by a chromogenic modification of the limulus amebocyte lysate test. Interleukin-6, CRP, transferrin, alpha-2-macroglobulin, albumin, apo-A, apo-B, IgG, IgA, IgM were determined by ELISA and nephelometrically. The clinical course was followed up by daily evaluation of the Apache-II-score. MAIN RESULTS: Demographic data were comparable in both groups. No differences of the Apache-II-score (verum group: 6.5 +/- 1.9 vs. controls: 6.8 +/- 1.8 on admission) were observed. Endotoxin and ENC levels were elevated at the end of the operation and seemed to have a trigger function for the acute phase response. However, there was no reduction (calculated as the area under the curve) in patients receiving the colostrum milk preparation throughout the observation period. Plasma levels of endotoxin binding proteins did not differ. Plasma IL-6 concentrations increased to maximal median values of 655 pg/ml in the verum and 786 pg/ml in the control group, respectively 2 and 6 h after surgery. In the colostrum group, there was a tendency to reduced IL-6 levels throughout the observation period. CRP-levels of all patients peaked 48 h after the operation but were lower (p = 0.034) in the verum group. CONCLUSION: This study revealed that endotoxemia occurs early in an elective non-intestinal surgical intervention, and is followed by a subsequent increase in mediators of the acute phase reaction. The prophylactic enteral application of a bovine milk preparation for two days in cardiac patients did reduce postoperative CRP-plasma levels but, contrary to a former double-blind study in abdominal surgery, failed to curtail perioperative endotoxemia. One reason could be the amount of colostrum preparation administered was too small.

Multimedia-driven teaching significantly improves students' performance when compared with a print medium.

BACKGROUND: In this study, we compared the educational value of a multimedia module about aortic valve replacement as a preparation for the operating room with a print medium of identical content. METHODS: One hundred twenty-six students were randomly assigned in a prospective study to either use the multimedia course (n = 69) or a print version (n = 57). A 20-item multiple-choice test was performed before and after learning with the respective medium. Both groups participated in an operation during which they were evaluated with 28 standardized tasks and questions. Individual motivation, computer literacy, and didactic quality of both media were assessed with psychometric tests. RESULTS: There were no significant differences in the multiple-choice pretest (multimedia, 30.6% +/- 12.4% versus print, 27.9% +/- 11.4%) and posttest responses (multimedia, 76.7% +/- 13.3% versus print, 76.9% +/- 11.1). Mean percentage of correct answers during the operation was 82.9% +/- 10% in the online group and 64.7% +/- 12% in the print group (p < 0.0001). The multimedia group needed significantly (p < 0.001) less study time (105 +/- 24 minutes) when compared with the text group (122 +/- 30 minutes). There were no statistically significant differences in motivation, computer literacy, and didactic quality of either medium. CONCLUSIONS: Regarding factual knowledge, there is no difference between multimedia-driven learning and a print medium. During heart operations, when understanding of complex temporal and spatial events is essential, students' performance is significantly improved by multimedia-enhanced teaching. The latter further proved to be more efficient in terms of study time.

Comparative evaluation of multimedia driven, interactive, and case-based teaching in heart surgery.

BACKGROUND: Multimedia-augmented instruction with various approaches is used in heart surgery. There is little evidence which instructional techniques and media are of advantage to impart knowledge more effectively and lead to better application of knowledge in the operation room. METHODS: Sixty-nine students learned with an interactive, case-based teaching (ICBT) course about aortic valve replacement. They were compared with historic controls exposed to identical information provided by a multimedia module presenting content systematically (SMM; n = 69) and a print medium (PM; n = 57). Motivation, computer knowledge, and didactic quality were evaluated with psychometric tests. All groups performed multiple choice pretests and posttests and participated in live surgery during which their performance was assessed. RESULTS: All groups had equal computer knowledge, but the ICBT group felt significantly less-motivated and more challenged. Multiple choice posttest results were comparable (ICBT 80.2% +/- 10.9%, SMM 76.7% +/- 13.3%, PM 76.9% +/- 11.1). During surgery, the ICBT (79.2% +/- 16%) and SMM groups (82.9% +/- 10%) performed significantly better than the PM group (64.7% +/- 12%; both p < 0.0001). Overall didactic assessment was significantly worse in the ICBT group when compared with the SMM and PM groups. CONCLUSIONS: For novices in heart surgery, ICBT was less motivating than traditionally structured content (SMM and PM). The ICBT did not improve performance in the operation room. However, both multimedia groups could better apply their knowledge during live surgery. The PM is as effective as multimedia when factual knowledge has to be retained.

Serum starvation and growth factor receptor expression in vascular smooth muscle cells.

BACKGROUND: Smooth muscle cell (SMC) proliferation in atherosclerosis is regulated through the interaction of growth factors like platelet-derived growth factor-BB (PDGF-BB) and insulin-like growth factor-1 (IGF-1) and their receptors (R). We hypothesized that serum starvation of SMCs may affect PDGFbeta-R and IGF-1-R expression and, consequently, the effect of their cognate ligands on SMC survival/proliferation. METHODS AND RESULTS: Serum starvation significantly increases PDGFbeta-R but not IGF-1-R mRNA and protein expression in SMCs. PDGF-BB stimulates cell survival but not proliferation in serum-starved SMCs of the synthetic phenotype, whereas SMCs of the contractile phenotype respond to PDGF-BB by a significant increase in proliferation. Immunohistochemical analysis of coronary atherosclerotic lesions reveals PDGFbeta-R expression in SMCs in the lamina fibromuscularis, but not in the media and in healthy parts of the arterial wall. No such differential expression was observed for IGF-1-R. CONCLUSIONS: Differential regulation of PDGFbeta-R and IGF-1-R expression by serum starvation might represent a mechanism for the control of SMC survival/proliferation in atherogenesis and restenosis. The distribution of PDGFbeta-Rs and IGF-1-Rs in atherosclerotic lesions may indicate an effect of serum starvation on SMCs in the arterial wall.

An image of mitral valve repair.

Mitral regurgitation is a severe problem of the mitral valve mechanism caused by many factors, including ischemic and nonischemic cardiomyopathy, inflammation, degeneration and others. Regardless of the cause of valve dysfunction, many changes in surgical approach have been undertaken. The pioneering work of Carpentier led to the era of mitral valve reconstruction a few decades ago. Understanding the different techniques applied in several pathoanatomic settings is of major interest. This review summarizes the indications and results of this specific surgical procedure in the setting of ventricular dysfunction by different causes.

Expression of mortalin in patients with chronic atrial fibrillation.

BACKGROUND: In myocardium of patients with chronic atrial fibrillation (AF) the expression of the mitochondrial heat shock proteins HSP60 and HSP10 is increased. They are responsible for folding and translocation of proteins inside the mitochondria. Import of these proteins is accomplished by mortalin. The aim of our study was to investigate if the expression of the heat shock protein mortalin is also increased in patients with AF. METHODS: Right atrial samples from 18 patients undergoing elective cardiac surgery were excised and immediately frozen in liquid nitrogen: 8 patients had chronic AF (> or = 3 month) and 10 patients were in sinus rhythm (SR). Mortalin was determined by SDS-PAGE, Western blot and quantified by optical densitometry. RESULTS: In myocardial samples from patients with chronic AF we found a more than 2-fold increase in mortalin expression. CONCLUSIONS: The increased expression of mortalin may represent an adaptive heat shock response to restore cellular homeostasis.

Intimal hyperplasia and expression of transforming growth factor-beta1 in saphenous veins and internal mammary arteries before coronary artery surgery.

BACKGROUND: The development of fibromuscular intimal hyperplasia and subsequent graft failure remains an urgent problem in cardiac surgery. Transforming growth factor-beta1 (TGF-beta1) is involved in the pathogenesis of arteriosclerosis through induction of extracellular matrix proteins. We tested the hypothesis that intimal hyperplasia is already present in human saphenous veins and left internal mammary arteries before coronary artery bypass surgery and is associated with an increased expression of TGF-beta1. METHODS: Forty-six segments of saphenous veins and 27 of left internal mammary arteries were collected from 50 patients undergoing coronary artery bypass surgery. Morphometric analysis was performed by microscopic computer analysis. Immunohistochemistry was performed with antibodies directed against TGF-beta1, its latent binding protein (LTBP-1) and its type 2 receptor (RII). RESULTS: The incidence of intimal hyperplasia was significantly higher in saphenous veins (67.4%) than in mammary arteries (29.6%; p < 0.05). Saphenous veins and mammary arteries with intimal hyperplasia expressed more TGF-beta1 (endothelial and intimal layers) and LTBP-1 (intimal and medial layers) when compared with corresponding vessels without hyperplasia (both groups p < 0.05). Endothelial and intimal RII expression was significantly higher in saphenous veins with intimal hyperplasia as compared with saphenous veins without hyperplasia (p < 0.05). Transforming growth factor-beta1 staining in the intima correlated with the presence of an intimal hyperplasia in saphenous veins (rho = 0.317) and mammary arteries (rho = 0.428). CONCLUSIONS: Local TGF-beta1 expression is associated with the presence of intimal hyperplasia in the examined vessels. Preexisting intimal hyperplasia is more prevalent and serious in saphenous veins than in left internal mammary arteries, giving further explanation to the superior long-term results of left internal mammary grafts.

The expression of heat shock protein 60 in myocardium of patients with chronic atrial fibrillation.

OBJECTIVE: Cardiomyocytes respond to stress with the expression of different heat shock proteins (HSP). HSP60 is induced by various stress factors. The aim of this study was to investigate the expression of HSP60 in human atrial fibrillation (AF). METHOD: Right atrial samples from 14 patients undergoing elective cardiac surgery were excised and immediately frozen in liquid nitrogen. Eight patients had chronic AF and six patients were in sinus rhythm. The HSP60 protein level was determined by SDS-PAGE, Western blot and quantified by optical densitometry according to the immunoreactive bands of actin. RESULTS: In myocardial samples from patients with chronic AF, we found a more than 2.5-fold increase in HSP60 expression compared to atrial myocardium of patients in sinus rhythm. CONCLUSION: This result indicates an up regulation of HSP60 in response to chronic atrial fibrillation.

Virtual reality and 3D visualizations in heart surgery education.

BACKGROUND: Computer assisted teaching plays an increasing role in surgical education. The presented paper describes the development of virtual reality (VR) and 3D visualizations for educational purposes concerning aortocoronary bypass grafting and their prototypical implementation into a database-driven and internet-based educational system in heart surgery. MATERIALS AND METHODS: A multimedia storyboard has been written and digital video has been encoded. Understanding of these videos was not always satisfying; therefore, additional 3D and VR visualizations have been modelled as VRML, QuickTime, QuickTime Virtual Reality and MPEG-1 applications. An authoring process in terms of integration and orchestration of different multimedia components to educational units has been started. RESULTS: A virtual model of the heart has been designed. It is highly interactive and the user is able to rotate it, move it, zoom in for details or even fly through. It can be explored during the cardiac cycle and a transparency mode demonstrates coronary arteries, movement of the heart valves, and simultaneous blood-flow. Myocardial ischemia and the effect of an IMA-Graft on myocardial perfusion is simulated. Coronary artery stenoses and bypass-grafts can be interactively added. 3D models of anastomotique techniques and closed thrombendarterectomy have been developed. Different visualizations have been prototypically implemented into a teaching application about operative techniques. CONCLUSIONS: Interactive virtual reality and 3D teaching applications can be used and distributed via the World Wide Web and have the power to describe surgical anatomy and principles of surgical techniques, where temporal and spatial events play an important role, in a way superior to traditional teaching methods.