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Biomedical subjects

Christoph Fink

Publications and source records attributed to Christoph Fink.

At least 19 recordsLinked to original sources

Long-term biocompatibility of a corrodible peripheral iron stent in the porcine descending aorta.

Currently there are no biodegradable stents available for treatment of vascular obstructions in patients with congenital heart defects. This study was performed to evaluate the safety of a corrodible stent produced from pure iron in a peripheral stent design (6-12mm diameter) in a slotted tube design similar to a commercially available 316-L stent which served as control. Both stents were implanted into the descending aorta of 29 minipigs with an overstretch injury without technical problems. Two animals died after the implantation not related to the iron stent. The remaining 27 minipigs were followed for 1-360 days. Histomorphometry and quantitative angiography showed no difference with regard to the amount of neointimal proliferation between 316-L and iron stents. Histopathological examination of heart, lung, spleen, liver, kidney and para-aortic lymphatic nodes demonstrated no signs of iron overload or iron-related organ toxicity. Adjacent to the iron stent struts, there was no evidence for local toxicity due to corrosion products. We conclude that iron is a suitable metal for the production of a large-size degradable stent with no local or systemic toxicity. A faster degradation rate, however, is desirable and further studies have to focus on the modification of the composition and design of the stent to expedite the degradation process.

Animals↗

Optimal pulmonary to systemic blood flow ratio for best hemodynamic status and outcome early after Norwood operation.

OBJECTIVE: Imbalances of pulmonary to systemic blood flow ratio (Q(p)/Q(s)) compounded with inadequate systemic oxygen delivery correlate with mortality after first-stage Norwood palliation of hypoplastic left heart syndrome. Mathematical models suggest that maximal systemic oxygen delivery occurs with Q(p)/Q(s) of less than 1. Whether this applies to clinical practice is unclear. This study evaluates the level of Q(p)/Q(s) that correlates with best hemodynamic status in the first 48 postoperative hours. METHODS: Hemodynamic data of 25 consecutive patients who underwent Norwood procedure from October 2002 to January 2005 were retrospectively analyzed. Data included, in particular, systemic venous and arterial oxygen saturation (SvO(2) and SaO(2), respectively), Q(p)/Q(s), lactate levels, and doses of required inotropes. Parameters were recorded 3 hourly. Data were assigned to three groups according to their corresponding Q(p)/Q(s): Groups 1, 2, and 3 for Q(p)/Q(s)< or =1, Q(p)/Q(s) between 1 and 2, and Q(p)/Q(s)> or =2, respectively. Thereafter, independent t-test or Fisher's exact test was used to reveal significant differences. Q(p)/Q(s) ratios and lactate levels were compared in hospital survivors and non-survivors. RESULTS: Out of 343 samples, 110, 184, and 49 were assigned to groups 1, 2, and 3, respectively. Group 1 (Q(p)/Q(s)< or =1) was characterized by lower SaO(2) (p<0.001) with similar SvO(2) (p=0.3 and p=0.5) and, therefore, higher systemic oxygen delivery (arteriovenous oxygen saturation difference, p<0.001; oxygen excess factor, p<0.001) compared to groups 2 and 3. However, lower mean arterial pressure (p=0.07 and p<0.001), higher lactate levels (p=0.009 and p=0.01), and norepinephrine doses (p=0.006 and p<0.001) highlighted worse hemodynamics. The best hemodynamic status corresponded to group 2. Q(p)/Q(s) remained above 1 in 21 survivors and was, most of the times, below 1 in four patients who died. Lactate levels were almost always above 4 mmol/l or increasing in non-survivors. CONCLUSIONS: Maximum oxygen delivery after Norwood operation occurs at Q(p)/Q(s) of less than 1. However, optimal hemodynamic status and end-organ function and higher survival correlates with Q(p)/Q(s) between 1 and 2. Thus, Q(p)/Q(s) should be targeted at 1.5 for improved course early after first-stage Norwood palliation.

Hemodynamics↗

Improved hemodynamics and outcome after modified Norwood operation on the beating heart.

BACKGROUND: Recently introduced cardiopulmonary bypass techniques to avoid circulatory arrest were proposed to improve organ function of the modified Norwood operation for hypoplastic left heart syndrome. This study compares postoperative hemodynamics and survival in patients who underwent Norwood procedure on the beating heart to those operated on with cardioplegic cardiac arrest. METHODS: Between October 2002 and January 2005, 26 consecutive patients aged 4 to 275 days (median, 9 days) and weighing 2.9 to 4.4 kg (median, 3.4 kg) underwent Norwood palliation: 13 with continuous coronary and systemic perfusion (group 1), and 13 with only continuous systemic perfusion but arrested heart (group 2). Standard hemodynamic measurements, lactate levels, arterial and superior vena cava oxygen saturations, and inotropic agents required for postoperative hours 0, 6, 12, 18, 24, and 48 were retrospectively analyzed. For univariate comparison of different variables, chi2 test, Fisher's exact test, or Student's t test was used as appropriate. RESULTS: In group 1 significantly higher mean arterial pressure (53 +/- 0.8 versus 50 +/- 1.2 mm Hg; p = 0.04), higher central oxygen saturation (54% +/- 1.1% versus 50% +/- 1.5%; p = 0.03), higher urinary output (5.3 +/- 0.4 versus 4.4 +/- 0.4 mL.kg(-1).h(-1); p = 0.09), lower lactate levels (2.4 +/- 0.1 versus 4.1 +/- 0.6 mmol/L; p = 0.009) with lower doses of norepinephrine (0.03 +/- 0.004 versus 0.14 +/- 0.03 microg.kg(-1).min(-1); p = 0.002) were recognized. Hospital mortality was 0% in group 1 and 38.5% (5 of 13) in group 2 (p = 0.04). Univariate analysis revealed mortality to be also correlated with preoperative intubation (p = 0.02) and the use of preoperative inotropic agents (p = 0.03). CONCLUSIONS: Avoidance of cardiac arrest by means of continuous coronary perfusion in addition to continuous systemic perfusion significantly improves postoperative hemodynamic performance and thus helps to reduce hospital mortality after the modified Norwood procedure.

Aorta, Thoracic↗

Comprehensive Aristotle score: implications for the Norwood procedure.

BACKGROUND: Aristotle score is emerging as a reliable tool to measure surgical performance. We estimated the comprehensive Aristotle score for the Norwood procedure, correlated it with survival, and considered its impact on surgical management of hypoplastic left heart syndrome. METHODS: Comprehensive Aristotle score was retrospectively calculated for 39 consecutive Norwood procedures performed from 2001 to 2004. Survival was estimated by the Kaplan-Meier method. RESULTS: The Aristotle scores ranged from 14.5 to 23.5 (mean, 19.12 +/- 2.52; median, 19.5). The score was 20 or greater in 44% (17 of 39) of cases. The most frequent patient-adjusted factors were aortic atresia (n = 16), interrupted aortic arch (n = 9), mechanical ventilation to treat cardiorespiratory failure (n = 19) and shock resolved at time of surgery (n = 13). Hospital mortality was 58.8% (10 of 17) in case of score of 20 or more and 9.1% (2 of 22) for score less than 20 (p = 0.0014). From 2003 on, all patients with a score less than 20 survived. Actuarial estimate of survival at 1 year is 56.2% +/- 7.9% and there have been no late deaths after 1 year. One-year survival is much lower (p = 0.001) for patients with scores of 20 or greater (29.4% +/- 11.05%) compared with those whose scores were less than 20 (77.3% +/- 8.9%). CONCLUSIONS: This study shows significant correlation of comprehensive Aristotle score with hospital mortality and late survival after Norwood palliation. It suggests that operative survival on the order of 90% may be achieved in patients with comprehensive complexity scores of less than 20. Efforts should be devoted to improve survival of high-risk patients (score > or = 20).

Cardiac Surgical Procedures↗

Restrictive left atrial outflow adversely affects outcome after the modified Norwood procedure.

OBJECTIVE: Moderate restrictive foramen ovale in neonates with hypoplastic left heart syndrome (HLHS) is considered to be favourable, reducing pulmonary overcirculation, before modified Norwood operation. However, some newborns with severe restriction of interatrial communication will have pulmonary vascular disease at birth, which correlates with increased perioperative mortality. This article studies the post-Norwood hemodynamic patterns and outcome for the particular group of HLHS newborns with restrictive left atrial outflow compared to other patients. METHODS: Restrictive left atrial outflow is defined as mitral and/or aortic atresia with intact ventricular septum, and restrictive foramen ovale, with 3 mm diameter or less with mean interatrial pressure gradient more than 5 mmHg at preoperative echo-Doppler. Four neonates fulfilled these criteriae among 18 consecutive patients, who underwent Norwood procedure from October 2002 to December 2003. Mean arterial pressure, heart rate, mean common atrial pressure, urinary output, central venous and arterial oximetry data, serum lactate levels, and dosages of milrinone, phentolamine and norepinephrine were collected at 0, 6, 12, 18 and 24 h after operation. Data were summarized as mean+/-SEM. For univariate comparison of different variables, Student's t-test was used. RESULTS: The postoperative hemodynamic pattern of patients with restrictive left atrial outflow was characterized by hypoxemia and low cardiac output. Arterial (66+/-3.0% vs 76+/-1.0%, P=0.01) and central venous (37+/-1.2 vs 52+/-1.1%, P=0.001) oxygen saturations were much lower than in patients without restriction. Arterio-venous oxygen saturation difference was wider (29+/-2.4% vs 23+/-0.9%, P=0.02) and serum lactate levels were higher (10.8+/-3.0 vs 2.8+/-0.2 mmol/l, P=0.03). Common atrial pressures were more elevated (12+/-0.8 vs 8+/-0.3 mmHg, P<0.001) and higher norepinephrine doses were needed (0.44+/-0.15 vs 0.06+/-0.01 microg/kg/min, P=0.03). The difference for the mean arterial pressures did not reach the significance level (48+/-2.0 vs 51+/-2.0 mmHg, P=0.2). Operative mortality was higher 75% (3/4) compared to 14.3% (2/14, P=0.04) for the other patients. CONCLUSIONS: Restrictive left atrial outflow adversely affects outcome after modified Norwood procedure. Abnormal pulmonary vasculature leading to insufficient pulmonary perfusion is incriminated. To improve outcome, implantation of larger size modified Blalock-Taussig or right ventricle-to-pulmonary artery shunts and routine use of postoperative mechanical assist device should be considered.

Aortic Valve↗

Assessment of subacute inflammatory and proliferative response to coronary stenting in a porcine model by local gene expression studies and histomorphometry.

The aim of the study was to analyse inflammatory and proliferative response early after coronary stenting by angiography, histomorphometry and local gene expression analysis using quantitative rt-PCR. Therefore, eight German domestic pigs underwent stenting of the left coronary artery. Selective coronary angiography was performed after 14 days. Explanted coronary arteries were examined histomorphometrically after methacrylate-embedding. Snap-frozen samples were examined for local gene expression of TGF-beta, TNF-alpha, GM-CSF, VEGF, PDGF and Fas Ligand (FasL) by real-time quantitative rt-PCR normalized to the housekeeping gene GAPDH and compared to unstented coronary arteries. All stented coronaries were patent with only little neointima formation. The median vessel diameter was 2.55 mm (range 2.43-2.68 mm). Histopathology revealed little inflammatory response limited to the tissue surrounding the stent struts; luminal area ranged from 84% to 91%. Compared to unstented control arteries, no significant differences in local gene expression were detected for VEGF, PDGF, TGF-beta, TNF-alpha and GM-CSF. Expression of FasL was upregulated as little as 1.7-fold (p=0.01). We conclude that, in native coronary arteries, no significant upregulation of investigated genes regulating vascular remodelling, inflammation or fibrogenesis was demonstrated 14 days after stenting. Whether upregulation of FasL as a marker gene of apoptosis is transient and biological significant requires further investigation.

Animals↗

Composition and in vitro biocompatibility of corroding tungsten coils.

The purpose of the article is to evaluate composition and biocompatibility of corroding mechanically detachable spirals (MDS, Balt Extrusion, Montmorency, France). Analysis of the material composition of corroding MDS coils was assessed by inductively coupled plasma atomic emission spectroscopy, inductively coupled plasma mass spectroscopy, and wavelength-dispersive x-ray spectrometry. Toxicity assays were performed with human venous endothelial cells, venous smooth muscle cells and fibroblasts. The analyses of the MDS coils demonstrated a tungsten content of the dissolving MDS spirals of > 99.9 mas%. In vitro, human endothelial, vascular smooth muscle cells and fibroblasts were not adversely affected by markedly elevated tungsten concentrations (60,500 microg/l) after 12 days in the culture medium. The examined cells showed an extensive vital growth on the coil surface. Corrosion of tungsten coils leads to markedly elevated tungsten levels in the culture medium. However, growth and vitality of endothelial cells, fibroblasts, and vascular smooth muscle cells are not adversely affected by elevated tungsten concentrations.

Biocompatible Materials↗

Secondary embolization of a Helex occluder implanted into a secundum atrial septal defect.

We report on a 2-year-old patient with atrial septal defect with a stretched diameter of 11 mm. The defect was closed uneventfully by use of a 25 mm Helex device. There was only trivial residual shunting (1 mm at the cranial margin of the device). After 36 hr, routine postinterventional echocardiography confirmed device embolization into the pulmonary artery. The child was asymptomatic. Transcatheter device retrieval with snares of different sizes, bioptomes, and retrieval forceps failed due to the mismatch of the diameter of the device and the small diameter of the pulmonary artery. Therefore, the device was retrieved surgically and the ASD closed by primary sutures. Secondary embolization of a Helex device complicated the closure of an uncomplicated atrial septal defect with a device-to-defect ratio according to the manufacturer's suggestion due to a mechanism not yet understood.

Coronary Angiography↗

Degradation of tungsten coils implanted into the subclavian artery of New Zealand white rabbits is not associated with local or systemic toxicity.

OBJECTIVE: To assess whether corrosion of tungsten coils is related to residual shunting and to evaluate whether elevated tungsten serum levels are associated with local or systemic toxicity. METHODS: Tungsten coils (SPI, Balt, France) were implanted into the subclavian artery of New Zealand white rabbits leading to a residual high-flow shunt in 5/10 rabbits. Serial serum tungsten levels, complete blood count and clinical chemistry were analysed prior to the implantation as well as 15 min, 2 and 4 months thereafter. After 4 months the rabbits underwent repeat angiography before they were sacrificed and the internal organs were evaluated histopathologically. RESULTS: Mean tungsten levels rose from 0.48 microg/l prior to the implantation to 12.4 microg/l 4 months post-implantation. The rise in serum tungsten levels was neither associated with residual shunting present at the time of implantation nor with residual shunting at the time of explantation. One animal had to be sacrificed because of non-resolving palsy of the upper extremity. The remaining animals had an uneventful clinical course with no signs of toxicity of the elevated tungsten levels. Histological examination revealed no evidence of local or systemic toxicity of the tungsten coils. CONCLUSION: Tungsten coils corrode and lead to a steady increase in serum tungsten levels starting as early as 15 min after implantation. Residual shunting does not seem to influence the kinetics of corrosion of tungsten coils. Despite markedly elevated serum tungsten levels 4 months after implantation degradation of tungsten coils is not associated with local or systemic toxicity.

Animals↗

Biocompatibility of corroding tungsten coils: in vitro assessment of degradation kinetics and cytotoxicity on human cells.

This study was performed to determine the in vitro degradation rate of tungsten coils and to evaluate the potential local toxicity of tungsten on human pulmonary arterial endothelial (EC) and smooth muscle cells (SMC) and human dermal fibroblasts (FB). Therefore, tungsten coils were immersed in Ringer's solution and loss of mass and increase in tungsten concentration in the electrolyte were assessed in relation to immersion time (maximum: 140 days). Primary cultures of EC, SMC and FB were grown on multiplates for 1-10 days with ascending concentrations (0.1-5000 microg/ml) of tungsten in the growth medium. Metabolic activity was assessed by the use of the WST-1 Test (Roche). The in vitro degradation rate of the tungsten coil was 29 microg/day. EC were most susceptible to tungsten with a LD50 of 50 microg/ml. In contrast, the LD50 for SMC was 100 and 1000 microg/ml for FB after 10 days of incubation. We conclude that, in vitro, degradation rate of tungsten coils is slow (29 microg/day). Very high (>50 microg/ml [normal serum value 0.0002 microg/ml]) tungsten concentrations are needed to result in local cytopathologic effects on human EC, SMC and FB. These results correspond to clinical observations demonstrating the absence of toxicity of degrading tungsten coils in adult and pediatric patients despite elevated serum tungsten levels.

Biocompatible Materials↗

Transcatheter closure of a multiperforated atrial septal defect extending from the oval fossa to the mouth of the inferior caval vein.

We report a novel technique using an Amplatzer atrial septal occluder to close a defect located in the inferior-posterior portion of the interatrial septum that extended into the mouth of the inferior caval vein. Because of the close relation of the defect to the inferior caval vein, the right atrial disc was opened into the inferior caval vein and pushed toward the right atrium by use of the delivery cable. There was no residual shunting immediately and 3 months after the intervention. We conclude that even defects located infero-posteriorly within the oval fossa may be successfully closed by transcatheter techniques using the Amplatzer device.

Cardiac Catheterization↗

Acute pulmonary edema caused by epoprostenol infusion in a child with scimitar syndrome and pulmonary hypertension.

INTRODUCTION: Intravenous epoprostenol is frequently administered in adults and children for treatment of pulmonary hypertension. Although generally safe, pulmonary edema has been described in a few case reports of adult patients with pulmonary veno-occlusive disease. CASE REPORT: We present an infant who had an operation for scimitar syndrome and abnormal drainage of the right pulmonary veins into the inferior vena cava who developed pulmonary edema while receiving a prostacyclin infusion. The typical partial anomalous pulmonary venous drainage was operatively corrected at 6 days of age, and an accompanying coarctation was resected. At 7 months of age, diagnostic cardiac catheterization was performed to evaluate suspected pulmonary hypertension. Pulmonary pressure was elevated to supra-systemic values, and obstructed venous drainage of the right hypoplastic lung was demonstrated. To decrease pulmonary hypertension during weaning and extubation, epoprostenol infusion was initiated. Sixty minutes after extubation, massive acute pulmonary edema lead to reintubation. Mean airway pressure of 16 mm Hg (21 mbar) with pure oxygen ventilation was initially required, with an oxygenation index of 14, a ventilation index of 36, and an alveolar-arterial oxygen tension difference of 541 mm Hg. After discontinuation of epoprostenol, weaning and extubation was successful. CONCLUSION: Pulmonary edema caused by prostacyclin infusion in patients with impaired postcapillary pulmonary drainage may also be encountered in children and has to be anticipated.

Acute Disease↗

Anterograde balloon valvuloplasty for the treatment of neonatal critical valvar aortic stenosis.

We report our experience with anterograde balloon valvuloplasty in 17 neonates treated between November 1996 and June 2001 for critical aortic stenosis. Patients with hypoplastic left heart syndrome were excluded. Anterograde balloon valvoplasty of the aortic valve was possible in all 17 patients. The mean peak systolic gradient prior to cardiac catheterization was 73 mm Hg (range, 30-117 mm Hg) and decreased to 37 mm Hg (range, 21-60 mm Hg) after the dilation. Aortic regurgitation after balloon valvoplasty was absent or mild in 14/17 patients, moderate in 2 patients, and severe in 1 patient. There was no mortality or echocardiographic evidence for aortic cusp perforation or mitral regurgitation associated with the procedure. Redilation was necessary in 3/17 patients. Two patients are awaiting elective Ross operation. One patient with endocardial fibroelastosis died at 11 months of age. Anterograde balloon valvoplasty can be safely and effectively performed to palliate neonates with critical aortic valve stenosis.

Aortic Valve Stenosis↗

[Interventional therapy of large veno-venous collaterals after univentricular palliation for congenital heart disease using the Starflex- and Amplatzer- PDA occluder].

UNLABELLED: Arterial hypoxemia is frequently observed after Fontan-like palliation of congenital heart defects. Whereas small systemic-to-pulmonary venous collaterals can easily be occluded by use of metal spirals, large collateral vessels may be therapeutically challenging. We report on two patients with arterial hypoxemia (transcutaneous oxygen saturations 72% and 82%, respectively) after Fontan-like operation. One patient was diagnosed with double inlet left ventricle, malposition of the great arteries and subaortic obstruction; another patient was diagnosed with mitral atresia, double-outlet right ventricle, malposition of the great arteries and hemiazygos continuity. In the first patient, a large venous collateral (measuring 16 mm in diameter) was observed connecting the superior vena cava and the right upper pulmonary vein. In the latter patient, hepatic fistulas drained systemic venous blood into an excluded hepatic vein. There was an associated patent fenestration of the conduit connecting the hepatic veins to the pulmonary artery. After occlusion of the supracardiac venous collateral with a 33 mm Starflex device, arterial oxxgen saturation rose to levels above 95%. The excluded hepatic vein was occluded with of an 10/8 mm Amplatzer PDA occluder and the fenestration was closed with a 17 mm Starflex device. Arterial oxygen saturations rose to 98%. CONCLUSION: Occlusion of large collateral vessels after Fontan-like palliation of congenital heart defects can be effectively performed using the Amplatzer PDA device and the Starflex device. Different occlusion devices are needed to address the morphological differences of the collateral vessels.

Child↗

Experimental ASD closure using autologous cell-seeded interventional closure devices.

OBJECTIVE: Atrial septal defect (ASD) occluders are permanent implants in paediatric cardiology which serve as mechanical shields until complete overgrowth and incorporation of the occluding device by autologous tissue has occurred. Thereafter, the foreign body material making up the device is dispensable and bears potential long-term adverse effects. Rapid, firm and complete incorporation into the atrial septal wall should be a prerequisite for biodegradable devices. In this study, the feasibility of using autologous cell-seeded devices was investigated by (a) testing the influence of a collagen coating on cellular stress resistance in vitro and (b) comparing the short-term effects between cell-seeded, collagen-coated and acellular ASD occluders in vivo. METHODS: Native and collagen-coated Dacon fabrics and Starflex-devices were pre-seeded with autologous fibroblasts (skin biopsy) and evaluated using various mechanical stress tests. In a sheep model interventionally created ASDs were closed using either autologous pre-seeded or conventional (acellular) Starflex-devices. RESULTS: ASD closure devices were successfully pre-seeded with autologous cells. The incubation period needed, the cellular density achieved and the mechanical stability of the cytolayer after mechanical stressing (implantation) were improved by applying a collagen matrix on the fabric. Compared to the thin layer of ingrown tissue seen on conventional occluders after 30 days in vivo, a thicker layer of organising, newly formed granulation tissue on pre-seeded collagen-coated devices embedded not only the Dacron fabric, but also completely covered the spring arms of the device underneath a layer of neo-endothelium. CONCLUSION: Autologous cell pre-seeding of interventional closure devices is feasible since the cells survive the mechanical stress encountered during implantation. Rapid, firm and complete ingrowth of occluder devices into a thicker layer of young fibrous granulation tissue can be achieved, but an increased thrombogenicity currently limits the in vivo application.

Absorbable Implants↗

Dissolution of tungsten coils does not produce systemic toxicity, but leads to elevated levels of tungsten in the serum and recanalization of the previously occluded vessel.

AIM: To evaluate the failure of mechanically detachable spirals produced from tungsten (MDS, Balt, Montmorency, France) and the toxicity of elevated levels of tungsten in the serum subsequent to their implantation. METHODS: We reviewed findings in 21 patients in whom tungsten coils had been used to occlude pathologic vessels, aneurysms and fistulas between 1996 and 1999. We achieved clinical follow-up, and measured renal and hepatic function, in 14 of the 21 patients. RESULTS: Decreased radiopacity of the coils was observed in 9 of 13 patients who had follow-up fluoroscopy during repeat cardiac catheterization. Repeat angiography of the vessel occluded by the coil was performed in 7 patients, 5 of whom showed recanalization. Levels of tungsten in the serum were analyzed 6 to 35 months after implantation of coils in 8 patients. The mean concentration was 6.43 micrograms/l, with a range from 2 to 14.4 micrograms/l, normal values being less than 0.2 microgram/l. CONCLUSION: Tungsten coils may dissolve over time and lead to markedly elevated levels of tungsten in the serum, with recanalization of previously occluded vessels. Despite lack of clinical and laboratory data in patients with elevated levels of tungsten in the serum, our study suggests that the clinical use of mechanically detachable coils produced from tungsten should no longer be recommended.

Adolescent↗