DEHP and its active metabolites: leaching from different tubing types, impact on proinflammatory cytokines and adhesion molecule expression. Is there a subsumable context?

INTRODUCTION: Di(2-ethylhexyl)phthalate (DEHP) is suspected to be toxic for several reasons. During contact with a lipophilic medium, DEHP leaks from polyvinylchloride (PVC), but its influence on inflammatory reactions remains unknown. We examined specific DEHP leaching out of different tubing types, the possibly modulated liberation of proinflammatory cytokines and the induction of adhesion molecule expression in primary endothelial cells. MATERIALS AND METHODS: Blood samples were circulated in traditional PVC, nodioctyl phthalate (DOP) PVC and heparin-coated PVC tubing within a Chandler loop model. The blood was tested for the concentration of DEHP and its active metabolites as well as the liberation of the proinflammatory cytokines TNFα and IL1ß. Furthermore, we exposed human endothelial cells to circulated blood and analysed them for the expression of the adhesion molecules ICAM-1, VCAM-1 and E-selectin. RESULTS: In contrast to the other tubing, PVC tubing showed significantly elevated DEHP levels, but no alteration was observed concerning a potential up-regulation of the cytokines or activation of the endothelial adhesion molecule receptors. CONCLUSIONS: Our data conclude that there is no correlation between DEHP leaching and the inflammatory response after ECC support, but this study showed that even DEHP-free material is leaching DEHP and its toxic metabolites.

Current concepts and new developments for autologous in vivo endothelialisation of biomaterials for intravascular applications.

Circulating endothelial progenitor cells (EPCs) in the peripheral blood of adults represent an auspicious cell source for tissue engineering of an autologous endothelium on blood-contacting implants. Novel materials biofunctionalised with EPC-specific capture molecules represent an intriguing strategy for induction of selective homing of progenitor cells. The trapped EPCs can differentiate into endothelial cells and generate a non-thrombogenic surface on artificial materials. However, the success of this process mainly depends on the use of optimised capture molecules with a high selectivity and affinity. In recent years, various biomedical engineering strategies have emerged for in situ immobilisation of patient's own stem cells on blood contacting materials. The realisation of this in vivo tissue engineering concept and generation of an endothelium on artificial surfaces could exceedingly enhance the performance of not only small calibre vascular grafts and stents, but also, in general all blood-contacting medical devices, such as heart valves, artificial lungs, hearts, kidneys, and ventricular assist devices.

Multiple giant coronary aneurysms--exclusion by vein graft interposition.

Coronary artery aneurysms (CAA) in adults are rare. However, the natural history of CAA is unknown since in adults it is predominantly atherosclerotic in origin. The clinical presentation, prognosis and management of giant CAA are not well defined due to limited experience and the low incidence of CAA. We present a case of successful exclusion of multiple giant CAA with an interposed reversed saphenous vein graft.

Resveratrol suppresses apoptosis in intact human cardiac tissue - in vitro model simulating extracorporeal circulation.

AIM: After cardioplegia and subsequent reperfusion of the myocardium as employed in cardiac surgery, ischemia/reperfusion injury of the myocardium can induce apoptosis. The aim of this study was to evaluate the anti-apoptotic properties of resveratrol, a phenolic phytoalexin present in grape skins and especially red wines during simulated cardioplegia (cp) and reperfusion (rep) in an in-vitro microperfusion model on human myocardium, which to our knowledge has not been investigated yet. METHODS: Cardiac specimens were retrieved from the right auricle of patients undergoing elective coronary artery bypass graft before induction of cardiopulmonary bypass. Cardiac specimens, with resveratrol (10 µM) (N.=15) and w/o resveratrol (control, N.=15) were exposed in vitro to varying periods of cp/rep (30/10, 60/20, 120/40 min) in a microperfusion chamber. For detection of apoptosis anti-activated-caspase-3, PARP-1 cleavage immunostaining and real-time PCR for gene expression of cardiac cytokines like BNP, NF-κB1, NF-κB2, E-Selectin, Troponin and TNF-α were employed. CONTROL GROUP: the longer the cp/rep period lasted the higher were the rate of anti-activated-caspase-3 positive cardiomyocytes (21.26±2.07% ­ 46.56±3.2%) and of PARP1-cleavage positive cardiomyocytes (23.29±2.16% ­ 36.86±2.11%). Resveratrol group: apoptosis was suppressed significantly (P<0.05). Anti-activated-caspase-3 positive cardiomyocytes (13.45±4.35% ­ 15.3±2.97%) and PARP1-cleavage positive cardiomyocytes (9.87±2.04% ­ 11.77±3.42%). Resveratrol significantly suppressed the expression of BNP, NF-κB2, E-Selectin, Troponin and TNF-α in vitro (P<0.05). CONCLUSION: Resveratrol significantly suppresses apoptosis under our applied in vitro conditions. This finding warrants further studies aiming suppression of ischemia/reperfusion injury in clinical settings.

Veins are no arteries: even moderate arterial pressure induces significant adhesion molecule expression of vein grafts in an ex vivo circulation model.

AIM: Coronary artery bypass grafting (CABG) is a standard procedure for treatment of coronary heart disease. Eighty percent of all CABGs are performed with venous grafts which then get exposed to an arterial pressure after surgery. This widely used procedure, however, is complicated by the development of alterations in the vein graft wall, leading to a decreased patency rate and graft failure. This study enlightens the influence of an even moderate arterial pressure on the gene expression of adhesion molecules in venous grafts which play a decisive role for the early induction of atherogenesis. METHODS: Segments of porcine vena jugularis and arteria carotis were mounted in a simulated bypass circuit and subjected to pulsatile flow. Vessel segments were examined for adhesion molecule expression with quantitative real-time - polymerase chain reaction (qRT-PCR) and adherence of leukocytes was observed by confocal laser scanning microscopy and scanning electron microscopy. RESULTS: Veins grafts subjected to an even moderate arterial pressure showed a 14-fold increase of ICAM-1 expression already after 4 hours. An arterial pressure of around 100/80 mmHg was enough to stimulate the adhesion molecule expression Furthermore it led to a 9-fold increase of leukocyte adhesion to the venous endothelium, but, in contrast this was not the case in arteries. CONCLUSION: This study showed, that already 100 mmHg upregulates the expression of several adhesion molecules in pig veins followed by increased adhesion of leukocytes. Therefore, our data demonstrate the advantage of arteries for CABG, and that new therapeutic strategies are urgently necessary to protect vein grafts either physically or pharmacologically if arteries are not available for CABG.

Suppressing apoptosis with milrinone simulating extracorporeal circulation: a pilot study.

BACKGROUND: After cardioplegia, ischemia/reperfusion injury can induce apoptosis. The aim of this study was to evaluate our ex vivo microperfusion model on human myocardium during simulated cardioplegia (cp) and reperfusion (rep). In addition, the aim was to verify the anti-apoptotic properties of the phosphodiesterase 3 inhibitor milrinone. METHODS: Cardiac biopsies were retrieved from the right auricle of patients undergoing elective CABG prior to induction of cardiopulmonary bypass. Biopsies were exposed to ex vivo conditions with varying periods of cp/rep (30/10, 60/20, 120/40 min). Group I consisted of untreated controls (n=15), Group II of treated controls who had cp/rep (n=15) while Group III had cp/rep+milrinone (n=15). For the detection of apoptosis, anti-activated caspase-3 and PARP-1 cleavage immunostaining were used. RESULTS: The percentage of apoptotic cardiomyocytes in Group I was significantly (P<0.05) lower compared to Group II, revealing a time-dependent increase. In Group III with milrinone treatment, apoptosis was significantly suppressed (P<0.05). CONCLUSIONS: Milrinone significantly suppressed apoptosis in our ex vivo setting. This finding warrants further study aiming to evaluate the potential beneficial effects of milrinone on the suppression of ischemia/reperfusion injury in a clinical setting.

Giant infantile fibroma of the right ventricle - surgical debulking and tumor plication.

Cardiac fibromas are rare lesions which occur predominantly in infants and children. In a 2-week-old premature infant with progressive exertional dyspnea, a huge cardiac tumor (5.0 x 4.5 x 5.0 cm) obstructing the right ventricle was diagnosed. Due to tumor progression with resulting obstruction of the right ventricular outflow tract (RVOT), surgery became necessary at 6 months. The tumor was partially resected, creating a crater-like defect, and the resection margins were subsequently plicated. Histological examination confirmed infantile fibroma. The combination of early diagnosis, the time and opportunity for cardiac development and immediate excision once symptoms occur is supposed to improve survival.

Comparison of imaging techniques in the diagnosis of bridging bronchus.

Bridging bronchus (BB) is a rare, congenital bronchial anomaly that is frequently associated with congenital cardiac malformations, especially left pulmonary artery sling. It represents an anomalous bronchus to the right originating from the left main bronchus. Discrimination from other bronchial anomalies is important, since BB is frequently associated with bronchial stenoses due to abnormal cartilage rings. This case study describes the findings of bronchoscopy, bronchography and multidetector computed tomography (MDCT) in three patients. Bronchoscopy was helpful in the description of the severity and length of bronchial stenoses. However, it was not possible to establish a diagnosis of BB based on this method in two patients, since it is difficult or even impossible to differentiate the bifurcation from the pseudocarina. It was not possible to establish the correct diagnosis in all patients based on bronchography or MDCT. MDCT was able to depict the relationship of bronchial and vascular structures, which is particularly important in patients with pulmonary artery sling. Multidetector computed tomography is preferable to bronchography as it is less invasive and due to its short acquisition time it can be performed in children with severe respiratory disease. In the current authors' experience, detection of cartilage rings still requires flexible bronchoscopy.

Aptamer-based isolation and subsequent imaging of mesenchymal stem cells in ischemic myocard by magnetic resonance imaging.

PURPOSE: Mesenchymal stem cells (MSC) seem to be a promising cell source for cellular cardiomyoplasty. We recently developed a new aptamer-based specific selection of MSC to provide "ready to transplant" cells directly after isolation. We evaluated MRI tracking of newly isolated and freshly transplanted MSC in the heart using one short ex vivo selection step combining specific aptamer-based isolation and labeling of the cells. MATERIALS AND METHODS: Bone marrow (BM) was collected from healthy pigs. The animals were euthanized and the heart was placed in a perfusion model. During cold ischemia, immunomagnetic isolation of MSC from the BM by MSC-specific aptamers labeled with Dynabeads was performed within 2 h. For histological identification the cells were additionally stained with PKH26. Approx. 3 x 10(6) of the freshly aptamer-isolated cells were injected into the ramus interventricularis anterior (RIVA) and 5 x 10(5) cells were injected directly into myocardial tissue after damaging the respective area by freezing (cryo-scar). 3 x 10(6) of the aptamer-isolated cells were kept for further characterization (FACS and differentiation assays). 20 h after cell transplantation, MRI of the heart using a clinical 3.0 Tesla whole body scanner (Magnetom Trio, Siemens, Germany) was performed followed by histological examinations. RESULTS: The average yield of sorted cells from 120 ml BM was 7 x 10(6) cells. The cells were cultured and showed MSC-like properties. MRI showed reproducible artifacts within the RIVA-perfusion area and the cryo-scar with surprisingly excellent quality. The histological examination of the biopsies showed PKH26-positive cells within the areas which were positive in the MRI in contrast to the control biopsies. CONCLUSION: Immunomagnetic separation of MSC by specific aptamers linked to magnetic particles is feasible, effective and combines a specific separation and labeling technique to a "one stop shop" strategy.

Coarctation of the pulmonary artery in neonates. Prevalence, diagnosis, and surgical treatment.

Stenosis or discontinuity of the central pulmonary artery at its bifurcation is often found in patients with congenital heart disease with intracardiac obstruction of the right side. The prevalence of this disease in autopsy cases is about 30%. The clinical prevalence has not been established yet because early diagnosis of this lesion is easily missed. Embryology suggests an etiologic similarity between coarctation of the aorta and this type of stenosis: both are caused by invasion of ductal tissue into the respective great artery. Therefore, the term coarctation of the pulmonary artery is appropriate. To recognize or exclude coarctation of the pulmonary artery, we examined left ventricular angiograms, aortograms, or both in the hepato-clavicular++ view in 25 consecutive neonates with severe arterial hypoxemia caused by right ventricular outflow tract obstruction. The prevalence of coarctation of the pulmonary artery was 36% (9/25). Fifteen neonates had two ventricles, and the other 10 had different types of univentricular heart. In eight cases no patent ductus arteriosus was found, and in none of these cases was coarctation of the pulmonary artery present. Conversely, in 9 of 17 neonates with a patent ductus arteriosus, coarctation of the pulmonary artery of different degree was demonstrated, even during prostaglandin E1 infusion in 7 neonates. With regard to surgical procedures, ductal tissue in the pulmonary artery wall should be completely removed. The aim is to establish adequate blood flow to both right and left pulmonary arteries. In this way unilateral hypoplasia of the arterial tree and consecutive growth of tortuous bronchial collaterals is prevented.

Cryopreserved and fresh antibiotic-sterilized valved aortic homograft conduits in a long-term sheep model. Hemodynamic, angiographic, and histologic comparisons.

There is a paucity of clinical and experimental data regarding the fate of cryopreserved valve aortic homografts. Fifteen lambs (mean age 4 months) underwent insertion of a valved aortic homograft between the right ventricle and pulmonary artery. In eight animals, the homografts were treated with antibiotics for 48 hours followed by up to 4 days of 4 degrees C storage (group A). In the other seven animals, the homografts were treated with antibiotics and cryopreserved at -196 degrees C (group B). The 12 long-term survivors were catheterized at 6 weeks and 4 months after implantation, at which time three animals from each group were killed. The remaining six animals were catheterized and killed at 9 months. There was no significant difference in transconduit gradient (p = 0.67) or resistance indexed to weight (p = 0.81) between groups A and B. The mean increase in transconduit gradient for both groups between catheterization at 6 weeks and 4 months was 73%, and weight increased by 51%. Histologic analysis focusing particularly on valve leaflet architecture and changes in the aortic wall revealed greater differences between individual animals and according to duration of implantation than differences between groups A and B. However, focal intracuspal thrombus of unknown significance was seen only in animals from group B. Although conduit valve leaflets generally remained free of calcification, calcification was prominent within the conduit wall of all animals. In conclusion, cryopreservation does not appear to adversely affect leaflet integrity and conduit function in this accelerated animal model relative to fresh homografts. This is in contrast to past clinical experience with homografts treated by freeze-drying and irradiation.

Modified Fontan operation in functionally univentricular hearts: preoperative risk factors and intermediate results.

BACKGROUND: The modified Fontan operation has been proposed as definitive palliation for an increasing variety of hearts with complex univentricular anatomy. To eliminate the influence of different surgical strategies, only patients undergoing total cavopulmonary anastomosis were included in this retrospective study. METHODS: Seventy-two patients had been operated on at ages ranging from 7 to 219 months, with 29 patients younger than 4 years. Twenty-three patients had mean pulmonary artery pressures higher than 15 mm Hg, elevated pulmonary arteriolar resistances (> 3 U.m2), or elevated end-diastolic ventricular pressure (> 12 mm Hg). Associated systemic or pulmonary venous anomalies were present in 22 patients (30%), and atrioventricular valve incompetence was present in 21 patients (29%). RESULTS: The overall mortality rate was 9.7% (7/72). Variables with significant effects on postoperative mortality were associated systemic or pulmonary venous anomalies, atrioventricular valve incompetence, mean pulmonary artery pressure greater than 15 mm Hg, and prolonged cardiopulmonary bypass time. Postoperative morbidity resulted mainly from atrial arrhythmia (20%). Clinical signs of protein-losing enteropathy or atrial thrombi were rare (3% and 6%, respectively). Postoperative hemodynamic data from 48 surviving patients (74%) revealed a mean transpulmonary gradient of 6.3 mm Hg, systemic venous pressure greater than 12 mm Hg in only 10 patients, and cardiac index less than 3 L.min-1.m-2 in 18 patients. CONCLUSION: In a high proportion of hearts with complex univentricular anatomy, associated anomalies, and borderline hemodynamics, the Fontan operation can be performed as a total cavopulmonary anastomosis with acceptable intermediate postoperative morbidity and hemodynamic results.

Aprotinin in fibrin tissue adhesives induces specific antibody response and increases antibody response of high-dose intravenous application.

BACKGROUND: In cardiac operations, aprotinin therapy is used either locally as a component of commercially available fibrin tissue adhesives, intravenously, or combined. Our aim was to examine the formation of aprotinin-specific antibodies with regard to the application mode. METHODS: Sera of 150 patients who had undergone cardiac operations and were receiving aprotinin therapy for the first time were sampled before the operation and at medians of 3.5 and 13.3 months after the operation. Aprotinin-specific IgG including all subgroups and aprotinin-specific IgE were analyzed. Aprotinin was given locally (as contained in fibrin sealant; n = 45; median dose, 6000 KIU), intravenously (n = 46; 2.000 x 10(6) KIU), and combined (n = 59; 2.012 x 10(6) KIU). RESULTS: At 3.5 months, the prevalence of aprotinin-specific IgG antibodies was 33% (15/45 patients) after local, 28% (13/46 patients) after intravenous, and 69% (41/59 patients) after combined exposure (P =.0001). At 13.3 months, the prevalence of aprotinin-specific IgG antibodies was 10% (4/41 patients) after local, 31% (13/42 patients) after intravenous, and 49% (28/57 patients) after combined exposure. Total aprotinin dose was similar in patients who were antibody positive and negative. Before the operation, no aprotinin-specific antibodies were detected. Aprotinin-specific IgE were not found after the operation. CONCLUSION: Local aprotinin contact induces a specific immune response and reinforces that of intravenous exposure. The antibody spectrum is identical to the immune response induced by intravenous exposure. Any exposure should be documented. For use in cardiac operations as a hemostyptic, the necessity itself and alternatives for aprotinin as a stabilizing agent merit consideration.

Fibrin sealant, aprotinin, and immune response in children undergoing operations for congenital heart disease.

OBJECTIVE: Most commercially available fibrin sealants contain aprotinin in doses of 1500 kallikrein inactivator units per milliliter. They are used in many operative disciplines. An elevated risk of hypersensitivity reactions exists at reexposure to aprotinin. Our aim was to examine the immunogenic potency of aprotinin as a fibrin sealant content. METHODS: We investigated 49 children with operatively treated congenital heart disease. All patients received aprotinin only topically as contained in fibrin sealant. Serum samples were drawn preoperatively, 1 week, 2 weeks, 6 weeks, and approximately 1 year after operation. They were analyzed for aprotinin-specific immunoglobulin G antibodies with a standard enzyme-linked immunosorbent assay and a fluorescence enzyme immunoassay for aprotinin-specific immunoglobulin E antibodies. RESULTS: At 1 week, 2 weeks, 6 weeks, and 1 year, we found prevalences of 8% (2 of 26), 8% (2 of 24), 6% (3 of 49), and 0% for aprotinin-specific Immunoglobulin E, and for aprotinin-specific immunoglobulin G 8% (2 of 26), 17% (4 of 24), 39% (19 of 49), and 12% (5 of 41). The doses of aprotinin given did not differ significantly in antibody-negative and antibody-positive patients; no significant factors could predict the immune response. CONCLUSIONS: Our findings show the existence of a subgroup of patients who had aprotinin-specific antibodies develop after topical aprotinin application. Any use of aprotinin must be carefully documented. If aprotinin use is planned in patients who previously underwent a surgical procedure, preexposure to aprotinin in any form must be sought to avoid unexpected anaphylactic reactions. The necessity itself and alternatives for aprotinin as a stabilizing agent in fibrin sealants merit consideration.

Successful lung transplantation for posttraumatic adult respiratory distress syndrome after extracorporeal membrane oxygenation support.

A severe adult respiratory distress syndrome after bilateral lung contusion was successfully treated by extracorporeal membrane oxygenation and subsequent double-lung transplantation in a 19-year-old man. The patient is fully rehabilitated 1 year after transplantation.

A new procedure for abdominal wound closure after pediatric liver transplantation: the "sandwich" technique.

Primary wound closure cannot always be achieved after pediatric liver transplantation (LTx). This may be due to lack of intraabdominal space from postanhepatic small bowel edema or oversized grafts despite partial LTx. For those instances we developed the "sandwich" technique. This procedure incorporates advantages of previous techniques with some additional advantages described herein. Use of polyglactin 910/silicone meshs in a sandwich fashion allows for one-stage permanent abdominal closure without major loss of body plasma fluids after pediatric LTx. So far our clinical experience with this technique has been very satisfying.

Preparatory surgical stent placement facilitating extracardiac vascular connections.

Native pericardium can be valuable material for the construction of extracardiac vascular connections. To avoid its scarring by adhesions and to preform future vascular connections, ringed polytetrafluoroethylene prostheses were implanted into the pericardial sac during staged operations for univentricular heart disease. At reoperation, extracardiac connections were found to be greatly facilitated by this approach.

Single-incision and single-element array electrode to lower the defibrillation threshold.

Occasional patients have excessive defibrillation energy requirements despite appropriate transvenous defibrillation lead position and the use of biphasic shocks. A single-element subcutaneous array electrode was implanted in 2 patients with a high defibrillation threshold. The array electrode was implanted through the same infraclavicular incision that was used for implantation of the transvenous lead. The defibrillation threshold decreased from 30 J to 15 J and from 24 J to 9 J with the subcutaneous array electrode.

Successful weaning of a transplanted heart from biventricular assist device.

Exceptionally few cases worldwide have survived weaning from a biventricular assist device following heart transplantation in contrast to those who underwent early retransplantation. We present a successful outcome after biventricular assist device implantation following initial biventricular failure after heart transplantation. Weaning could be performed after 1 week, although pulmonary vascular resistance remained markedly elevated.

Successful management of junctional tachycardia by hypothermia after cardiac operations in infants.

BACKGROUND: Junctional ectopic tachycardia is an early postoperative complication after intracardiac repair of congenital heart disease, especially in infants. Because of the high ventricular rate and the usually poor response to antiarrhythmic drugs, this condition is associated with a high morbidity and mortality. The purpose of this study was to assess the safety and efficacy of moderate body surface hypothermia in the treatment of postoperative junctional ectopic tachycardia in infants. METHODS: Six consecutive infants with postoperative junctional ectopic tachycardia (mean age at operation, 14 weeks) were treated with surface cooling. The decision to start treatment was based on the definition of a critical heart rate (180 to 200 beats/min) in the presence of junctional ectopic tachycardia diagnosed according to established criteria. Moderate hypothermia (rectal temperature between 32 degrees and 34 degrees C) was achieved by placing ice bags on the child's body surface. The patients were sedated, mechanically ventilated, and paralyzed. RESULTS: Mean interval between diagnosis of tachycardia and initiation of hypothermia was 4 hours. Rectal temperature was rapidly (within 1 hour) lowered to 32 degrees to 34 degrees C in all 6 patients. This significantly lowered the tachycardia rate from 219 +/- 27 beats/min to 165 +/- 25 beats/min (mean +/- standard deviation; p < 0.001). Three patients with signs of low cardiac output had restoration of stable hemodynamics once the tachycardia rate had been decreased by hypothermia. Cooling was maintained for a period of 24 to 88 hours (mean, 59 hours). No serious side effects were observed. CONCLUSIONS: Early institution of moderate hypothermia by body surface cooling was a safe and efficient measure to control ventricular rate in infants with postoperative junctional ectopic tachycardia.