Advanced training model for beating heart coronary artery surgery: the Zurich heart-trainer

Objective: Coronary artery surgery with beating heart technique is gaining increasing popularity. However, it is a challenging technique even for well-trained cardiac surgeons. Thus, a training model for beating heart surgery was developed to increase safety and accuracy of this procedure. Methods: The model consists of differentially hardened polyurethane resembling mechanical properties of the human heart. The covering used in this model is a 1:1 replica of the human thoracic wall with optionally embedded skeletal structures. Sternotomy, lateral thoracotomy or trocar placement is possible to access the lungs, the pericardium and the heart with adjacent vessels. Disposable artificial coronaries variable in size, wall quality or wall thickness are embedded in the synthetic myocardium. Two-layer vessels, which can simulate dissection, are available. Bypass conduits utilize the same material. Coronaries/bypasses as well as part of the ascending aorta are water-tight and can be rinsed with saline. Lungs can be inflated. A purpose-built pump induces heart movement with adjustable or randomized stroke volume, heart rate and arrhythmia induction. Results: The model was tested in a recent ‘Wet-Lab' course attended by 30 surgeons. All conventional instruments and stabilizers with standard techniques can be used. Training with beating or non-beating heart was possible. Time needed for an anastomosis was similar to clinical experience. Each artificial tissue showed its individual nature-like qualities. Various degrees of difficulty can be selected, according to stroke volume, heart rate, arrhythmia, vessel size and vessel quality. The model can be quickly and easily set up and is fully reusable. Conclusions: The similarity to human tissue and the easy set-up make this completely artificial model an ideal teaching tool to increase the confidence of cardiac surgeons dealing with beating heart and minimally invasive surger

Left ventricular assist device as bridge to heart transplantation - lessons learned with the MicroMed DeBakey axial blood flow pump

Objective: The MicroMed DeBakey left ventricular assist device (LVAD) axial blood flow pump was used as bridge to heart transplantation (HTx) in patients with terminal heart failure. The aim was to evaluate this novel mechanical circulatory support system in regard to overall outcome. Methods: Prospective study in 15 HTx candidates (mean age 40±7 years) with terminal heart failure and maximal medical treatment due to ischemic cardiomyopathy (CMP, n=5), dilated CMP (n=3), restrictive CMP (n=2), unclassified CMP (n=1), metabolic CMP (n=1), valvular CMP (n=1) and congenital CMP (n=2). All patients were implanted with a MicroMed DeBakey LVAD. A rescue procedure was necessary in eight critical patients, while seven underwent elective LVAD implantation. Procedures were performed via median sternotomy, in normotherm femoro-femoral CPB (mean duration 59±1 min). Oral Marcoumar© (INR 2.0-3.0) and Aspirin© (100 mg daily) were started as soon as possible. Patients were discharged into a specialized rehabilitation clinic from which it was possible to release them home after a few weeks. Results: Successful implantation and discharge from ICU (mean stay 10±7 days) was possible in 11 patients. Seven were transplanted (mean support 50.7 days) and one is awaiting HTx (support >310 days) in the comfort of his home (NYHA I). Survival was 100% among the transplanted patients. Of the seven elective implants, five, and of the eight rescue procedures three patients underwent successful HTx. Four patients died early, while three patients died late on pump support due to intracranial hemorrhage (n=2, 73 and 76 days) and chest infection (n=1, 124 days). All survivors were discharged from hospital, with significant decrease in NYHA class (mean 3.8-2.4 (n=11)). Treadmill testing showed increased exercise tolerance, from 35 to 71 W (n=4). Plasma BNP values (mean 950-162 ng/l (n=4)) and pulmonary resistance (mean 316-194.5 dyne s/cm5 (n=3)) decreased significantly during LVAD support. Conclusions: The MicroMed DeBakey LVAD is simple to implant; outpatient treatment is safe and efficient. Patients' condition and pulmonary resistances normalize within 6 weeks, making previously considered inoperable patients amenable for HTx. HTx can be performed in low-risk situation, allowing better donor-recipient matching and improving overall outcom

Expression of adhesion molecules and cytokines after coronary artery bypass grafting during normothermic and hypothermic cardiac arrest

Objective: Cardiac surgery with cardiopulmonary bypass (CPB) results in vascular injury and tissue damage which involves leukocyte-endothelial interactions mediated by cytokines and adhesion molecules. This study was designed to demonstrate the effect of normothermic and hypothermic CPB to cytokine and soluble adhesion molecule levels in adults and to determine whether these levels correlate to the patients postoperative course. Design and patients: In 25 patients after normothermic and in 25 patients after hypothermic coronary artery bypass grafting with cardiopulmonary bypass (CPB), blood samples for cytokine and soluble adhesion molecule analysis were taken preoperatively, 24, 36, 48 h, and 6 days postoperatively. Soluble adhesion molecules (sE-selectin, sICAM-1) were measured by ELISA and cytokines (TNF-α, IL-6, IL-8) by chemilumenscent-immunoassay. Clinical data were collected prospectively. Results: Postoperatively, adhesion molecule and cytokine levels were significantly elevated after CPB. Mean plasma levels of sICAM-1 was 2.4-fold higher after 6 days. Mean plasma concentration of sE-selectin peaked after 48 h with a 2-fold increase compared to normothermic conditions. In the hypothermia group sICAM-1, sE-selectin, IL-6, and IL-8 showed significantly higher levels (P≪0.0057, P≪0.0012, P≪0.0419, P≪0.0145) after 24 h compared to the normothermia group. No clinical differences were seen. Conclusion: Adhesion molecules and cytokines are elevated after CPB. Patients after hypothermic CPB show significant higher sICAM-1, sE-selectin, IL-6, and IL-8 levels after 24 h compared to normothermic conditions. These results are mainly due to longer CPB and crossclamp times but do not alter the patient's postoperative cours

Preoperative predictors of recurrent atrial fibrillation late after successful mitral valve reconstruction

Objective: Late outcome after mitral valve repair was examined to define preoperative predictors of recurrent atrial fibrillation late after successful mitral valve reconstruction. Methods: One hundred and eighty-nine patients, 112 with preoperative sinus rhythm and 72 with preoperative chronic or intermittent atrial fibrillation, were followed for 12.2±10 years after valve repair. Clinic, hemodynamic end echocardiographic data were entered into Cox-regression and Kaplan-Meyer analysis to assess predictors for recurrent atrial fibrillation late after successful mitral valve repair. Results: Univariate and multivariate predictors for recurrent atrial fibrillation late after successful mitral valve reconstruction were preoperative atrial fibrillation (P=0.0001), preoperative antiarrhythmic drug treatment (P=0.005), heart rate (P=0.01), left ventricular ejection fraction (P=0.01) and increased left ventricular posterior wall thickness (P=0.05). Patients>57.5 years with a mean pulmonary artery pressure ≥23mm Hg and a history of preoperative antiarrhythmic drug treatment had an odds ratio of 53.33 (95% confidence limits 6.12-464.54) for atrial fibrillation late after successful mitral valve repair. Conclusion: Older patients with a history of atrial fibrillation, antiarrhythmic treatment or an elevated pulmonary artery pressure may present atrial fibrillation late after successful mitral valve repair. They could be considered for combined mitral valve reconstruction and surgery for atrial fibrillation even though sinus rhythm is present preoperativel

Inhibition of ICAM2 induces radiosensitisation in oral squamous cell carcinoma cells

We recently identified genes and molecular pathways related to radioresistance of oral squamous cell carcinoma (OSCC) using Affymetrix GeneChip. The current study focused on the association between one of the target genes, intercellular adhesion molecule 2 (ICAM2), and resistance to X-ray irradiation in OSCC cells, and evaluated the antitumor efficacy of combining ICAM2 small interfering RNA (siRNA) and X-ray irradiation. Downregulation of ICAM2 expression by siRNA enhanced radiosensitivity of OSCC cells with the increased apoptotic phenotype via phosphorylation (ser473) of AKT and activation of caspase-3. Moreover, overexpression of ICAM2 induced greater OSCC cell resistance to the X-ray irradiation with the radioresistance phenotype. These results suggested that ICAM2 silencing is closely related to sensitivity of OSCC cells to radiotherapy, and that ICAM2 may be an effective radiotherapeutic target for this disease

The City Biosphere

This paper introduces a new experimental city generation, assembly and development platform, the urban mutations platform. We describe in detail a methodology for modeling urban systems and their dynamics, based on self-organization principles. The urban area is seen as an organism comprised of different “body parts”, the urban subunits. Upon creation of an initial 3D urban environment, it is possible to add to the subunits the so-called mutations, i.e. structural and functional components that can have beneficial or detrimental effects to the future city development. After addition of the mutations we allow the city to reorganize itself and observe possible changes in the urban configuration. These changes can be directly correlated to the added mutations and their urban qualities and allow us to probe the effect that different structural and functional elements have on the dynamic behaviour of the city, when placed at specific locations

Erythropoietin protects from reperfusion-induced myocardial injury by enhancing coronary endothelial nitric oxide production

OBJECTIVE: Cardioprotective properties of recombinant human Erythropoietin (rhEpo) have been shown in in vivo regional or ex vivo global models of ischemia-reperfusion (I/R) injury. The aim of this study was to characterize the cardioprotective potential of rhEPO in an in vivo experimental model of global I/R approximating the clinical cardiac surgical setting and to gain insights into the myocardial binding sites of rhEpo and the mechanism involved in its cardioprotective effect. METHODS: Hearts of donor Lewis rats were arrested with cold crystalloid cardioplegia and after 45 min of cold global ischemia grafted heterotopically into the abdomen of recipient Lewis rats. Recipients were randomly assigned to control non-treated or Epo-treated group receiving 5000 U/kg of rhEpo intravenously 20 min prior to reperfusion. At 5 time points 5-1440 min after reperfusion, the recipients (n=6-8 at each point) were sacrificed, blood and native and grafted hearts harvested for subsequent analysis. RESULTS: Treatment with rhEpo resulted in a significant reduction in myocardial I/R injury (plasma troponin T) in correlation with preservation of the myocardial redox state (reduced glutathione). The extent of apoptosis (activity of caspase 3 and caspase 9, TUNEL test) in our model was very modest and not significantly affected by rhEpo. Immunostaining of the heart tissue with anti-Epo antibodies showed an exclusive binding of rhEpo to the coronary endothelium with no binding of rhEpo to cardiomyocytes. Administration of rhEpo resulted in a significant increase in nitric oxide (NO) production assessed by plasma nitrite levels. Immunostaining of heart tissue with anti-phospho-eNOS antibodies showed that after binding to the coronary endothelium, rhEpo increased the phosphorylation and thus activation of endothelial nitric oxide synthase (eNOS) in coronary vessels. There was no activation of eNOS in cardiomyocytes. CONCLUSIONS: Intravenous administration of rhEpo protects the heart against cold global I/R. Apoptosis does not seem to play a major role in the process of tissue injury in this model. After binding to the coronary endothelium, rhEpo enhances NO production by phosphorylation and thus activation of eNOS in coronary vessels. Our results suggest that cardioprotective properties of rhEpo are at least partially mediated by NO released by the coronary endothelium

The City Biosphere: A novel theoretical and experimental methodology for the identification of catalysing mutations in city generation, assembly and development

This paper introduces a new experimental city generation, assembly and development platform, the urban mutations platform. We describe in detail a methodology for modeling urban systems and their dynamics, based on self-organization principles. The urban area is seen as an organism comprised of different \u93body parts\u94, the urban subunits. Upon creation of an initial 3D urban environment, it is possible to add to the subunits the so-called mutations, i.e. structural and functional components that can have beneficial or detrimental effects to the future city development. After addition of the mutations we allow the city to reorganize itself and observe possible changes in the urban configuration. These changes can be directly correlated to the added mutations and their urban qualities and allow us to probe the effect that different structural and functional elements have on the dynamic behaviour of the city, when placed at specific locations

Advanced training model for beating heart coronary artery surgery: the Zurich heart-trainer

Objective: Coronary artery surgery with beating heart technique is gaining increasing popularity. However, it is a challenging technique even for well-trained cardiac surgeons. Thus, a training model for beating heart surgery was developed to increase safety and accuracy of this procedure. Methods: The model consists of differentially hardened polyurethane resembling mechanical properties of the human heart. The covering used in this model is a 1:1 replica of the human thoracic wall with optionally embedded skeletal structures. Sternotomy, lateral thoracotomy or trocar placement is possible to access the lungs, the pericardium and the heart with adjacent vessels. Disposable artificial coronaries variable in size, wall quality or wall thickness are embedded in the synthetic myocardium. Two-layer vessels, which can simulate dissection, are available. Bypass conduits utilize the same material. Coronaries/bypasses as well as part of the ascending aorta are water-tight and can be rinsed with saline. Lungs can be inflated. A purpose-built pump induces heart movement with adjustable or randomized stroke volume, heart rate and arrhythmia induction. Results: The model was tested in a recent ‘Wet-Lab' course attended by 30 surgeons. All conventional instruments and stabilizers with standard techniques can be used. Training with beating or non-beating heart was possible. Time needed for an anastomosis was similar to clinical experience. Each artificial tissue showed its individual nature-like qualities. Various degrees of difficulty can be selected, according to stroke volume, heart rate, arrhythmia, vessel size and vessel quality. The model can be quickly and easily set up and is fully reusable. Conclusions: The similarity to human tissue and the easy set-up make this completely artificial model an ideal teaching tool to increase the confidence of cardiac surgeons dealing with beating heart and minimally invasive surger