Establishment of a resazurin-based aortic valve tissue viability assay for dynamic culture in a microphysiological system.

BACKGROUND/AIM: Tissue pathogenesis of aortic valve (AV) stenosis is research focus in cardiac surgery. Model limitations of conventional 2D culture of human or porcine valvular interstitial/endothelial cells (VIC/VECs) isolated from aortic valve tissues but also limited ability of (small) animal models to reflect human (patho)physiological situation in AV position raise the need to establish an in vitro setup using AV tissues. Resulting aim is to approximate (patho)physiological conditions in a dynamic pulsatile Microphysiological System (MPS) to culture human and porcine AV tissue with preservation of tissue viability but also defined ECM composition. MATERIALS/METHODS: A tissue incubation chamber (TIC) was designed to implement human or porcine tissues (3×5 mm2) in a dynamic pulsatile culture in conventional cell culture ambience in a MPS. Cell viability assays based on lactate dehydrogenase (LDH)-release or resazurin-conversion were tested for applicability in the system and applied for a culture period of 14 days with interval evaluation of tissue viability on every other day. Resazurin-assay setup was compared in static vs. dynamic culture using varying substance saturation settings (50-300µM), incubation times and tissue masses and was consequently adapted. RESULTS: Sterile dynamic culture of human and porcine AV tissue segments was established at a pulsatile flow rate range of 0.9-13.4µl/s. Implementation of tissues was realized by stitching the material in a thermoplastic polyurethane (TPU)-ring and insertion in the TIC-MPS-system. Culture volume of 2 ml caused LDH dilution not detectable in standard membrane integrity assay setup. Therefore, detection of resazurin-conversion of viable tissue was investigated. Optimal incubation time for viability conversion was determined at two hours at a saturated concentration of 300µM resazurin. Measurement in static conditions was shown to offer comparable results as dynamic condition but allowing optimal handling and TIC sterilization protocols for long term culture. Preliminary results revealed favourable porcine AV tissue viability over a 14 day period confirmed via resazurin-assay comparing statically cultured tissue counterparts. CONCLUSIONS: Human and porcine AV tissue can be dynamically cultured in a TIC-MPS with monitoring of tissue viability using an adapted resazurin-assay setup. Preliminary results reveal advantageous viability of porcine AV tissues after dynamic TIC-MPS culture compared to static control.

Characterization of thoracal fat depots - expression of adipokines and remodeling factors and impact of adipocyte conditioned media in fibroblast scratch assays.

Adipose tissue is not only a connective tissue but also an endocrine organ secreting adipokines like Leptin and Adiponectin, lipokines such as palmitoileic acid and extracellular vesicles. These factors and the expression of matrix remodeling enzymes impact surrounding tissues via paracrine effects. The expression of selected secretion factors and the effect of adipocyte conditioned media from four thoracal adipose tissue origins - subcutaneous, perivascular, pericardial and epicardial adipose tissues - in a fibroblast proliferation/wound healing scratch assay model were investigated. Results were compared directly and according to the type 2 diabetic mellitus (T2DM) status of the patients the tissues are originated from. Adipocyte conditioned media from non-diabetic patients resulted in a significant higher scratch closure rate compared to the media with T2DM background. Linoleic acid incubation in scratch assay resulted in a reduced scratch closure rate. Leptin, Adiponectin and Visfatin/Nampt expression and MMP2, MMP9 and FSTL1 mRNA levels did not vary according to T2DM subgroups directly, leading to the assumption that these factors are not causal for scratch assay effects observed. In contrast significant mRNA expression differences were monitored between the thoracal tissue origins implying variations in the local effects of the different adipose tissue depots.

Readmission to the intensive care unit after cardiac surgery: a single-center experience with 7105 patients.

AIM: Identification of patients at high risk for readmission to the Intensive Care Unit (ICU) after cardiac surgery is paramount. We evaluated the clinical characteristics of readmitted patients and identified perioperative prognostic variables for ICU readmission. METHODS: A total of 7105 patients who underwent cardiac surgery between 2007 and 2010 and discharged after a primary stay in the ICU were reviewed retrospectively. Of these, 7.8% (554) patients were readmitted. The reasons for readmission and postoperative course were analyzed. Perioperative risk factors for readmission were determined by multivariate regression analysis. RESULTS: Mortality of patients after readmission was 13.6% compared with 0.2% without recidivism (P<0.0001). Mean length of stay in hospital of patients requiring readmission was 24.9 ± 19.1 days and significantly longer compared to all other patients 12.3±8.4 days (P<0.0001). The main reasons for readmission were respiratory failure (39.0%) and cardiovascular instability (26.2%). Complex cardiac surgery, aortic surgery and extended stay in the ICU were the most powerful variables to predict ICU readmission. CONCLUSION: ICU readmission was related to complex surgery and associated with impaired outcome. Respiratory complications were the most common reasons for readmission. Predictive renal and pulmonary risk factors indicate the need of preoperative preconditioning and patient selection.

Intra-aortic balloon pump implantation does not affect long-term survival after isolated CABG in patients with acute myocardial infarction.

BACKGROUND: Intra-aortic balloon pump (IABP) is an established therapy to support patients with heart failure during coronary artery bypass grafting (CABG). The impact of the timing of IABP on the hospital course and on follow-up is of particular clinical interest. The purpose of this study was to analyze the relationship between the time of IABP implantation and its impact on early, mid- and long-term survival in patients with acute myocardial infarction (AMI) who underwent emergent CABG for NSTEMI and STEMI. METHODS: A total of 472 patients with AMI (NSTEMI and STEMI) underwent emergency CABG at our institution; 158 of them additionally received IABP support. Fifty-seven (36 %) patients received preoperative and 101 (64 %) patients underwent intraoperative IABP implantation. Endpoints were in-hospital und follow-up (mean duration 37 ± 28 months) survival. RESULTS: Overall in-hospital mortality was 17.1 % (n = 27): 17.6 % (n = 10) in the preoperative group and 16.8 % (n = 17) in the intraoperative group ( P = ns). Mid- and long-term survival rates were comparable for both groups 78.6 % vs. 73.7 %, 71.4 % vs. 68.7 % and 64.3 % vs. 54.6 % at 1, 3 and 5 years, respectively ( P = ns). CONCLUSION: This study demonstrates that CABG with IABP support in high-risk patients with AMI can be performed with acceptable in-hospital and long-term survival rates. The decision for IABP placement should consider the preoperative clinical condition and the intraoperative course of each patient. IABP placement does not appear to affect the long-term outcome after isolated CABG in patients with AMI.

[Transapical aortic valve implantation--indications, risks and limitations]. / Transapikaler Aortenklappenersatz--Indikationen, Risiken und Grenzen.

Calcified aortic stenosis is the predominant valve disease in the western world. Currently, surgical aortic valve replacement is the gold standard procedure for symptomatic severe aortic stenosis that can be performed with low morbidity and mortality. The prevalence of aortic stenosis increases with age, and the incidence of several comorbidities also unavoidably elevates the risk of surgical treatment. Therefore, the most adequate and gentle treatment is needed especially for this population. Since the first transcatheter aortic valve implantation (TAVI) was performed in 2002, the main implanting routes are the transfemoral, retrograde access through the common femoral artery, and the antegrade, transapical approach via anterolateral minithoracotomy. Meanwhile, TAVI has become an alternative treatment for patients who are not suitable candidates for surgical therapy in some centers.The initial clinical results are promising and have confirmed the feasibility of this technique. Due to the restricted long-term data, conventional aortic valve replacement still remains the standard for the treatment of aortic stenosis. Selection of the suitable therapy approach (surgical replacement, transfemoral or transapical aortic valve implantation) must consider each patient's specific risk profile and individual indication. Prospective, randomized trials will be necessary to assess the individual survival benefit of TAVI for various risk populations and to extend the indication.

Immunosuppression using the mammalian target of rapamycin (mTOR) inhibitor everolimus: pilot study shows significant cognitive and affective improvement.

UNLABELLED: Immunosuppression using calcineurin inhibitors (CNIs) is accompanied by neuropsychiatric side effects, which counteract longevity and quality of life benefits in 10% to 28% of patients. Following the availability of the mammalian target of rapamycin (mTOR) inhibitors, it became possible to replace CNI without increasing the risk of acute graft rejection. mTOR, a member of the phosphatidyl inositol 3' kinase family, is a downstream target of brain-derived neurotrophic factor, which has been implicated in the pathophysiology and treatment of several psychiatric disorders. Preclinical evidence has implicated the mTOR pathway in synaptic plasticity and fear memory consolidation and reconsolidation. METHODS: In the present study we prospectively evaluated the psychiatric outcomes of CNI-free immunosuppression in adult maintenance heart transplant recipients (n = 9; age: 66.1 +/- 6.1) using the Wechsler Memory Scale-Revised (WMS-R), Symptom Checklist-90-Revised (SCL-90-R), Beck Depression Inventory (BDI), Trail Making Tests A and B, Digit Span (DS), and Hamilton Depression Scale (HAMD). RESULTS: Four weeks after switching to CNI-free immunosuppression using everolimus, BDI (Z = -1.14; P = .048), Trail Making tests A and B (Z = -2.52; P = .012), WMS-R (Z = 2.37; P = .018), and SCL-90-R (Z = -2.37; P = .018) were all significantly improved while DS (Z = -1.18; P = .236) and HAMD (Z = -0.595; P = .552) remained unchanged. CONCLUSION: This report describes favorable psychiatric outcome variables using everolimus in maintenance heart transplant recipients. CNI-free immunosuppression with everolimus might provide significant improvement in memory, concentration, and overall psychiatric symptoms among heart transplant recipients.

Coronary surgery for acute coronary syndrome: which determinants of outcome remain?

BACKGROUND: The mortality risk associated with coronary artery bypass grafting (CABG) after acute myocardial infarction remains controversial. The objective of the present study was therefore to analyze the outcome and predictors of in-hospital mortality in patients (pts) referred to CABG with acute coronary syndrome (ACS). PATIENTS AND METHODS: Between January 2003 and May 2005, a total of 3,127 pts underwent primary isolated CABG at our institution, including 220 pts with ACS. Out of these, unstable angina pectoris was present in 88 pts (group I), 97 pts (group II) had non-ST-elevation infarction, whereas 35 pts (group III) had ST-elevation infarction. Clinical data, in-hospital morbidity and mortality were recorded and studied retrospectively. RESULTS: Overall in-hospital mortality was 6.4% (n = 14) in the complete cohort, being 2.2% in group I (n = 2), 9.2% in group II (n = 9) and 8.5% (n = 3) in group III (P < 0.05). Logistic regression and receiver operating characteristic analyses identified age, NYHA, ejection fraction < 45%, catecholamine support, cardiogenic shock, renal disease and the additive EuroSCORE > 10 (P < 0.0001) as significant predictors related to in-hospital mortality. The mean time from the onset of symptoms to revascularization differed significantly between survivors (5.1 +/- 2.7 h) and no survivors (11.4 +/- 3.2 h) (P < 0.0007) in the STEMI group. Preoperative cTnI did not provide any prognostic information. CONCLUSION: CABG in pts with ACS can be performed with good clinical results. The clinical outcome is particular depending on the different groups of ACS. Therefore an individual risk stratification of each pts in ACS is necessary. The time interval of 6 h seems to be crucial as prognostic variable in the STEMI-group.

Influence of extra corporeal circulation on myocardial oxygen tension: results of an animal model.

BACKGROUND: Experimental data have shown the potential risk of cellular damage of the myocardium during extra corporeal circulation (ECC). The influence of ECC on myocardial oxygen tension however remained unclear. Therefore, the influence of ECC on the oxygen tension in a beating heart was investigated. METHODS: In a pig animal model flexible pO2 microcatheters were positioned in the midmyocardium of the left ventricle and the skeletal muscle and tissue oxygen tension during ECC were monitored and compared with data of a control group without ECC. RESULTS: ECC and unload of the heart caused a significantly higher increase of myocardial pO2 than in a non-ECC control group. CONCLUSION: Our findings show the beneficial effect of ECC on myocardial pO2. This may support the use of ECC in coronary artery bypass grafting because the potential myocardial injury due to ECC is not related to myocardial ischemia. On the contrary, myocardial pO2 was even increased during extracorporeal circulation in this study.

Coronary reoperation with and without cardiopulmonary bypass.

Redo coronary artery bypass grafting (CABG) is still associated with increased morbidity and mortality compared to primary operation. Myocardial protection is one of the key issues in redo on pump CABG and is still a matter of debate. Off pump redo CABG seems to be an attractive alternative as native coronary blood flow remains and cross clamping of the aorta is avoided. The aim of this retrospective study was to compare the outcome of redo CABG with and without CPB. From 1/1998 to 5/2004 redo CABG was performed in 195 patients (pts): 162 male (83.1%) and 33 female (16.9%) pts, age 66 +/- 9 years. In 160 pts, CPB with isolated antegrade myocardial protection was used for redo CABG. Off pump redo CABG was performed in 35 pts (30 male (85.7%) and 5 female (14.3%), age 67 +/- 8 years). Perioperative overall mortality rate was 3.6% (n = 7) and comparable in both groups (on pump 3.8% versus off pump 2.9%; p = 0.90), as well as perioperative myocardial infarction, intraaortic balloon pump implantation rate and secondary morbidity. Complete revascularization was achieved in 139 pts (86.9%) after on pump CABG and in 17 pts (48.6%) of the off pump group (p < 0.01). The average number of grafts was significantly higher in the on pump group (2.8 +/- 0.78 versus 1.6 +/- 0.6; p = 0.04).Furthermore, 20 pts (12.5%) in the on pump group died during follow-up (50 +/- 16 months). Five pts (25.0%) died due to cardiac reasons. In the off pump group 3 pts (8.6%) died during follow-up (44 +/- 13 months), noncardiac related. Overall survival was 83.8% in the on pump group and 88.6% in the off pump group (p = 0.92). On pump redo CABG and off pump redo CABG can be safely performed with low mortality and morbidity. Off pump redo CABG might be limited due to incomplete revascularization.

Perforation of the ascending aorta: a late complication of superior vena cava stenting.

Intravascular stenting of the superior vena cava (SVC) is an established therapy in patients with SVC syndrome. Late complications include re-occlusion, stent infection, migration, and perforation. Affection of the greater thoracic vessels is rare and life-threatening when it occurs. We present a case of ascending aorta laceration as a late complication of SVC stenting. Surgical therapy included excision of the aortic lesion and pericardial patch repair. This case illustrates successful management of a complication after palliative stenting of the SVC.

Lactatdehydrogenase (LDH) prior and post implantation of ATS heart valves.

Establishing guidelines towards an assessment of prostheses dysfunction using LDH as a marker is difficult as shown by [M. Suedkamp, A.J. Lercher, F. Mueller-Riemenschneider, K. LaRosee, P. Tossios, U. Mehlhorn, Hemolysis parameters of St Jude Medical hemodynamic valves in aortic position, Int. J. Cardiol (95) (2004) 89-93]. In response to their work we would like to add our data concerning ATS valves (AP) and say a word of caution in interpreting an increase of LDH values.

Coronary surgery in dialysis-dependent patients with end stage renal failure.

The number of patients with dialysis-dependent end stage renal failure (ESRF) and coronary heart disease (CAD) has increased in recent years. Coronary artery bypass grafting (CABG) has become the standard treatment for CAD in this patient group, but is still considered as a risk procedure due to increased mortality and morbidity. In a retrospective study we analyzed our clinical results of isolated CABG in 40 dialysis-dependent patients with ESRF (5 female and 35 male, mean age 65+/-8.4 years) and the use of extracorporeal circulation. The perioperative control group comprised 51 patients (10 female and 41 male, mean age 67+/-7.3 years) with normal renal function and isolated CABG. Demographic and preoperative data were comparable in both groups. Hospital mortality was 2.5% in patients with ESRF and 0% in patients with normal renal function. Morbidity was comparable in both groups. The mean number of grafts was 3.1+/-0.9 in the dialysis group and 2.9+/-0.8 in the control group. In the follow-up of the dialysis group (34+/-23 months) 8 patients died. CABG in patients with dialysis-dependent ESRF can be performed with good clinical results and morbidity comparable to patients with normal renal function.

[Surgical therapy of infective endocarditis]. / Chirurgische Behandlung von Klappenendokarditiden.

Therapy of infective endocarditis (IE) remains a particular challenge due to a relative high morbidity and mortality. Cardiac surgery is established as a cornerstone in therapy for native valve endocarditis (NVE) as well as for prosthetic valve endocarditis (PVE) and is required in 30% of patients with active IE. The basic aim of surgery in IE is the radical debridement of infected tissue and reconstruction of valve function either by reconstructive valve surgery or valve replacement. Indication for surgery depends on several clinical variables, the main indication remains heart failure due to severe heart valve defects or prosthetic valve dysfunction. Surgical therapy of NVE can be performed with good clinical results in the early and late follow-up. Surgical therapy of PVE is still associated with quite high mortality up to 80% in some risk groups. This indicates the particular importance of focus evaluation and antibiotic prophylaxis after primary surgery for infective endocarditis.

Influence of radiographic contrast media on myocardial tissue oxygen tension: NaCl-controlled, randomised, comparative study of iohexol versus iopromide in an animal model.

It was tested whether a bolus injection of 10 ml radiographic contrast medium (iopromide vs. iohexol), compared to a 10 ml NaCl bolus and administered into the left anterior descending artery (LAD) of farm pigs, influenced the tissue pO2 in the territory of this artery. The radiographic contrast media and the NaCl bolus were given in randomised order. The mean pO2 LAD fell from initially 40.3+/-10.9 mmHg to a minimal value of 22.5+/-8.9 mmHg 241+/-44 sec after injecting the iopromide bolus, with this result representing a mean decrease of 44.2% (p=0.0003). The initial pO2 (baseline) was reached again after approximately 10 minutes. The mean pO2 LAD fell from the initial value of 34.5+/-14.6 mmHg to a minimal value of 29.4+/-13.9 mmHg 171.7+/-11.9 sec after injection of the iohexol bolus, with this result representing a mean decrease of 14.8% (p=0.0003). The baseline pO2 was reached again after approx. 5 minutes. The drop in the pO2 after iopromide administration was significantly larger than that after iohexol (p=0.0001), and also the time after which the baseline pO2 is reached again was considerably shorter for iohexol (p=0.001). The two radiographic contrast media did not influence the tissue pO2 in either the territory of the right coronary artery or in skeletal muscle. Injection of a NaCl bolus into the LAD influenced neither the tissue pO2 of the territory of the LAD nor that of the RCA or of the skeletal muscle. The tissue temperature, heart rate and the systolic and diastolic blood pressure were not affected during the three injections. Injection of radiographic contrast media into a coronary artery can lead to a distinct, local microcirculatory impairment in the myocardial territory supplied by this artery. In this case, the extent of the microcirculation impairment seems to depend not only on the viscosity of the contrast media but rather also on its chemotoxicity.

[Surgical therapy of traumatic cardiologic intervention]. / Chirurgische Therapie nach traumatischen interventionellen Koronarläsionen.

Coronary perforation and entrapment of catheter materials are rare, but life-threatening complications, which often require emergency cardiosurgical treatment. Surgical options include tamponade drainage, coronary artery bypass grafting, perforation suturing, and removal of catheter materials. Surgical strategies are not standardized but mainly depend on the surgical anatomy. This is in particular true for the removal of the catheter remnants (stent, guidewire). Keeping this in mind, these patients can be treated with good clinical results.