bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Allogeneic versus Xenogeneic Auxiliary Organ Perfusion in Liver Failure Reveals Superior Efficacy of Human Livers
Authors: Pascher A. , Sauer I.M. , Neuhaus P.
Published: January 2018

Purpose:

To compare the efficacy of allogeneic and xenogeneic extracorporeal liver perfusion (ECLP).

Methods:

An Internet-based keyword search was performed in the established online databases. Univariate and multivariate analysis of variance (general linear method) were performed.

Results:

Data from 198 patients were included in the statistical analysis, 142 of whom were treated by ECLP using porcine livers. Baboon livers were used in 29 patients, human livers in 14, and other or mixed species in 13 patients. Pig liver perfusions resulted in a 20% long-term-survival whereas the use of human livers was significantly more successful (survival rate (SVR) 43%, p<0.05). Baboon livers also revealed superior success (41%; p<0.05). Twenty-three patients were treated after 1991, 12 surviving long-term (52%). The latter all belonged to a group of 14 patients who received combined treatment consisting of ECLP and LTx (SVR-86% in this subgroup).

Conclusion:

Allogeneic ECLP was accompanied by significantly improved outcome compared with discordant xenogeneic ECLP. The role of hyperacute rejection in acute liver failure with reduced complement levels remains controversial. Physiologic disparity between pig and man may be the even more decisive determinant of outcome.
Extracorporeal Liver Support: Porcine or Human Cell Based Systems?
Authors: Gerlach J.C. , Zeilinger K. , Sauer I.M. , Mieder T. , Naumann G. , Grünwald A. , Pless G. , Holland G. , Mas A. , Vienken J. , Neuhaus P.
Published: January 2018

Initial results of the clinical use of primary porcine liver cells for extracorporeal liver support are being reviewed as the cell source is controversial. According to Eurotransplant data 20 −25% of explanted donor livers are not transplanted, due to factors such as steatosis or cirrhosis. This number corresponds to the number of patients with acute liver failure who require bridging therapy to transplantation. Primary human liver cells from transplant discards can be isolated, purified and maintained in bioreactors and provide an alternative for cell-based extracorporeal liver support therapy. A four-compartment bioreactor enables recovery from preservation and isolation injury in a three-dimensional network of interwoven capillary membranes with integrated oxygenation, rendering the liver cells from these discarded donor organs viable for clinical utilization. Patient contact with additional animal-derived biomatrix and fetal calf serum can be avoided. The initiation of an in vitro cultivation phase allows cell stabilization, quality control, and immediate availability of a characterized system without cryopreservation. The hypothesis of this paper is that with appropriate logistics and four-compartment bioreactor technology, cells from human liver transplant discards can serve the demand for cell-based therapy, including extracorporeal liver support.
Xenotransplantation for Liver Therapy Or: Can Porcine Hepatocytes Generate Physiological Functions Sufficient for a Human Patient in ALF?
Authors: Hammer C.
Published: January 2018

Detailed knowledge about physiology, biochemistry and function is required before artificial liver devices using porcine hepatocytes may be used successfully. Improvement of cell culture conditions and tissue engineering may permit the generation of human hepatocytes as substitutes for grafts in a transplantation setting.

The physiological functions of xenografts have to be compatible with those of the recipient. However, first observations indicate that most physiological interaction in widely divergent species combinations such as pig and man are considerably different. This may be crucial for the selection of a suitable organ, tissue or cell for a clinical set-up.

These differences vary from organ to organ and cell to cell. Only very conservative molecules, like for example insulin or calcitonin function properly in both species, while others such as complement, albumin and erythropoietin do not fulfill their task properly or not at all.
Results from EuCliD® (European Clinical Dialysis Database): Impact of shifting treatment modality
Authors: Godino J.I. Merello , Rentero R. , Orlandini G. , Marcelli D. , Ronco C.
Published: January 2018

Background:

The use of biocompatible high-flux membranes is more efficient than low-flux membranes in controlling a number of hemodialysis-related diseases. The aim of this cooperative study was to evaluate the 6-month effect of a switch from low- to high-flux dialysers on patients treated in 39 Spanish dialysis centres.

Methods:

The clinical data used in this analysis were prospectively collected by the EuCliD® database, developed to monitor the quality of treatment delivered in a large network of European Dialysis Centres. Inclusion criteria for the study were the condition of end-stage renal disease (ESRD) on chronic hemodialysis and low-flux dialysis for at least six months before the switch to high-flux dialysis. Of 1,543 patients enrolled in the study between 2000 and 2001, 1,046 patients were considered for the analysis. 497 patients were excluded because they did not complete the follow-up. Outcome measures were the reduction of pre-dialysis beta-2 microglobulin, the improvement of anemia or reduction in rHu-EPO dose required to maintain best correction of anemia, reduction of inflammatory parameters (CRP), improvement in lipid profile (Total and HDL cholesterol, tryglycerides), maintenance of nutritional status. Albumin and “dry” (post-hemodialysis) body weight were both evaluated as nutritional indexes.

Results:

During the six months of high-flux hemodialysis, there was a significant increase in hemoglobin (from 11.55±1.41 to 11.88±1.43 g/L; p<0.001). Considering the temporarily untreated patients on a 0 U/week dose, erythropoietin remained stable (from 5,670±4,199 to 5,657±4,411 U/week). During the second part of the follow-up, the lipid profile significantly improved (Fig. 3). Total cholesterol and triglycerides decreased significantly (p<0.001), while HDL cholesterol increased (p=0.006). Calculated levels of LDL cholesterol also significantly decreased (p=0.001). Dry body weight remained stable (64.7±11.9 vs. 64.7±12.0 kg) as well as in albumin levels (3.93±0.43 vs. 3.94±0.43 g/dL) between the two modalities of treatment. The level of ß2-microglobulin significantly decreased during high-flux dialysis (33.5±14.4 vs. 26.3±8.6 mg/dL, p<0.001).

Conclusion:

All above mentioned results may have as a common denominator an improved blood purification from uremic toxins and a reduced level of chronic sub-clinical inflammation. All together, these results seem to confirm the superiority of high-flux dialysis in terms of clinical and physiological outcomes.
Strategy for the Treatment of Noncompliant Hypertensive Hemodialysis Patients
Authors: Ross E.A. , Pittman T.B. , Koo L.C.
Published: January 2018

Hypertensive hemodialysis patients noncompliant for their medications do not benefit from pharmacologic advances in the treatment of high blood pressure, and increase their already high risk of cardiovascular complications. The medical staff often becomes frustrated by severe hypertension in those who refuse to take medicines at home, drink excessive fluids, miss multiple dialysis sessions and sign-off dialysis early. In addition to addressing the psychosocial, financial, educational and substance abuse problems which contribute to noncompliance, we have developed a medication strategy to serve as an at least interim means of lowering blood pressure. Antihypertensive agents which have long half-lives in renal failure (lisinopril) and/or are intrinsically long acting (transdermal clonidine and amlodipine) were administered on dialysis days by the unit personnel to those patients who did not or would not take that or any dose on their own. The lisinopril and amlodipine were assured to have been taken on at least the dialysis days (thrice weekly), and the clonidine patch replaced weekly. Sixteen patients were thus treated when they failed to reliably self-administer medications. They had a significant decline in the pre-dialysis systolic pressure of 15 mm Hg (175 ± 6 to 160 ± 5 mm Hg), diastolic of 12 mm Hg (103 ± 3 to 91 ± 3 mm Hg), and mean pressure of 13 mm Hg (127 ± 4 to 114 ± 4 mm Hg). There was an improvement in post-dialysis blood pressures, with the mean pressure declining 13 mm Hg from 110 ± 4 to 97 ± 4 mm Hg. Many individuals had erratic blood pressure control, having intermittently missed dialysis and hence unit-administered medicine, as well as continued fluid or drug abuse. The patients had uniformly excellent acceptance of this regimen, even spontaneously requesting it, and had no appreciable adverse effects. In summary while noncompliance is being addressed by the entire medical team, dialysis unit administration of long-acting medicines helps many hypertensive dialysis patients who would otherwise be at increased risk for severe cardiovascular complications.
Ginsenoside Rb1 Enhances Peripheral Nerve Regeneration across Wide Gaps in Silicone Rubber Chambers
Authors: Chen Y.-S. , Wu C.-H. , Yao C.-H. , Chen C.-T.
Published: January 2018

Silicone rubber chambers filled with collagen containing ginsenoside Rb1 (GRb1) were used to repair lesioned rat sciatic nerves with 15-mm gaps between stumps. Six weeks after implantation, histology of the nerve regenerated in the chambers filled with GRb1 and collagen contained larger axons than those in the chambers with collagen only. This study showed that the GRb1 could exert a positive influence on nerve regeneration when using silicone rubber tubes.
Dialysis in Acute Renal Failure: Is More Better?
Authors: Clark W.R. , Kraus M.A.
Published: January 2018

An increasing body of evidence indicates therapy dose and intensity influence the outcome of dialyzed ARF patients. However, a number of unanswered questions remain on this issue. These questions need to be addressed in future prospective, controlled trials that assess the effect of dose and intensity on outcome both within and between the various ARF renal replacement therapies, with appropriate and clinically relevant control arms. Such investigations should provide guidelines ultimately for the dialytic management of critically ill patients with ARF.
Recovery of Rats with Fulminant Hepatic Failure by using a Hybrid Artificial Liver Support System with Polyurethane Foam/Rat Hepatocyte Spheroids
Authors: Sakiyama R. , Nakazawa K. , Ijima H. , Mizumoto H. , Kajiwara T. , Ito M. , Ishibashi H. , Funatsu K.
Published: January 2018

We studied the recovery of rats with fulminant hepatic failure (FHF) by treating them with our original hybrid artificial liver support system (HALSS). FHF was induced by a two-thirds partial hepatectomy and 10 minutes of hepatic ischemia. Rats with FHF were treated with a polyurethane foam/spheroid HALSS including 2.0 T 108 hepatocytes for 1 hour (HALSS group, n = 5), and with the same system without hepatocytes in the artificial liver module as a control experiment (sham-HALSS group, n = 3). The level of blood constituents, ammonia, glucose and creatinine, showed no major difference between the two groups at the end of treatment. All rats in the sham-HALSS group died within 5 hours after treatment. However, the level of blood constituents of rats with FHF in the HALSS group improved with time, and all rats in the HALSS group recovered. Liver tissue of rats treated with HALSS showed cell mitosis and improvement from injury. These results indicated that our HALSS has a strong possibility to induce recovery from hepatic failure.
Model Study of Blood Flow through a Stent in the Aorto-Iliac Bifurcation
Authors: Kertzscher U. , Affeld K. , Scheckel M.
Published: January 2018

Atherosclerotic ailments play a major role in industrial societies. Atherosclerotic disease causes stenotic narrowing of the arterial vessel system. These narrow passages can be widened with balloon angioplasty and stents are introduced to keep the passage open. In this study, stents designed for the aorto-iliac bifurcation are considered. Most of these stents used in peripheral arteries are self-expanding stents made from Nitinol, a thermo-reactive alloy. The insertion is done under radiographic control. However, the delicate metallic structure of the stent usually casts only a weak radiographic shadow and thus is difficult to detect. A stent with an innovative radio opaque tantalum marker (Luminexx®, C.R. BARD – Angiomed, Karlsruhe), overcomes this problem. However, the markers extend into the blood flow and the question arises whether the markers may cause the generation of thrombi. In a model study in an enlarged model of the aorto-iliac bifurcation with an inserted stent the flow was visualized. The enlarged scale permits the observation and video recording of the flow in great detail. The Reynolds similarity is kept. A subsequent analysis of the flow in the vicinity of the markers shows a short residence time. These results indicate that the additional markers do not increase the risk of thrombus generation.
Polymerized Degradable Hyaluronan – a Platform for Stent Coating with Inherent Inhibitory Effects on Neointimal Formation in a Porcine Coronary Model
Authors: Heublein B. , Evagorou E.G. , Rohde R. , Ohse S. , Meliss R.R. , Barlach S. , Haverich A.
Published: January 2018

Biodegradable hyaluronan (hyaluronic acid, HA) made insoluble by self-cross-linking in the presence of N-(3-dimethylaminopropyl)-N′-ethyl carbodiimide (EDC) has been used to cover stents. The maximum polymer-mass on a 16-mm stainless steel stent is approximately 2 mg. During manual crimping and simulated application, the loss of polymerized HA is negligible. The insoluble HA coating has an advantageous inherent antiproliferative effect regarding neointimal formation after local vessel wall injury (overstretch model) and leads to a reduced inflammatory response compared to uncoated stainless-steel stents, used as control, in undiseased pig coronary arteries, over a follow-up period of four weeks. Thus, cross-linked HA stent coating warrants further research as an interactive degradable biomaterial with an inherent inhibitory effect on neointimal formation as a possible biomatrix for local drug delivery to reduce restenosis rate.
Necrotizing Fasciitis Successfully Treated with Extracorporeal Blood Oxygenation and Ozonization (EBOO)
Authors: Di Paolo N. , Bocci V. , Cappelletti F. , Petrini G. , Gaggiotti E.
Published: January 2018

A case of necrotizing fasciitis in a dialysis patient is described. Since traditional therapies were unsuccessful, extracorporeal blood oxygenation and ozonation (EBOO) was tried. This technique is no longer in the experimental stage and is used routinely in our hospital. Patient condition improved radically after EBOO.
Protease Removal by Means of Antiproteases Immobilized on Supports as a Potential Tool for Hemodialysis or Extracorporeal Blood Circulation
Authors: Grano V. , Diano N. , Portaccio M. , De Santo N. , Di Martino S. , Rossi S. , De Santo L.S. , Salamino F. , Mattei A. , Mita D.G.
Published: January 2018

This work studies protease concentration decrease in aqueous solutions in contact with a modified polyethersulphone graft membrane onto which antiproteases were immobilized. As a model of protease/antiprotease interaction, elastase and α1-antitrypsin were used. Experiments were carried out either under fixed amounts of immobilized antiproteases and variable protease concentration or under fixed protease concentration and variable amounts of immobilized antiproteases. In both cases, active protease concentrations decreased with increase in contact time with the membrane. Experimental conditions under which active elastase concentration becomes zero were also found. Occurrence of the same phenomenology has also been ascertained with protease solutions obtained from human blood neutrophils. The membrane activated with α1-antitrypsin showed differential inhibitory power on elastase and cathepsin G.

This technology could open new perspectives in manufacturing new membranes to be used in hemodialysis and extracorporeal circulation when elastase is released.
A Hybrid Mock Circulatory System: Development and Testing of an Electro-hydraulic Impedance Simulator
Authors: Kozarski M. , Ferrari G. , Clemente F. , Górczyńska K. , De Lazzari C. , Darowski M. , Mimmo R. , Tosti G. , Guaragno M.
Published: January 2018

Mock circulatory systems are used to test mechanical assist devices and for training and research purposes; when compared to numerical models, however, they are not flexible enough and rather expensive.

The concept of merging numerical and physical models, resulting in a hybrid one, is applied here to represent the input impedance of the systemic arterial tree, by a conventional windkessel model built out of an electro-hydraulic (E-H) impedance simulator added to a hydraulic section. This model is inserted into an open loop circuit, completed by another hybrid model representing the ventricular function.

The E-H impedance simulator is essentially an electrically controlled flow source (a gear pump). Referring to the windkessel model, it is used to simulate the peripheral resistance and the hydraulic compliance, creating the desired input impedance. The data reported describe the characterisation of the E-H impedance simulator and demonstrate its behaviour when it is connected to a hybrid ventricular model. Experiments were performed under different hemodynamic conditions, including the presence of a left ventricular assist device (LVAD).
Treatment of Insulin Resistance in Uremia
Authors: Stefanović V. , Nešić V. , Stojimirović B.
Published: January 2018

Insulin resistance is a characteristic feature of uremia. As long as the hyperinsulinemia adequate to overcome the insulin resistance, glucose tolerance remains normal. In patients destined to develop type 2 diabetes, the ß cell compensatory response declines, and relative, or absolute, insulin deficiency develops. At this point glucose intolerance and eventually frank type 2 diabetes occur. Insulin resistance and concomitant hyperinsulinemia are present irrespective of the type of renal disease. Several studies have confirmed that hemodialysis (HD) treatment significantly improves insulin resistance. Both CAPD and CCPD are shown to improve insulin resistance in uremic patients. Comparing the effect of PD and HD treatment, it was found that the CCPD group has significantly higher insulin sensitivity than the HD group with the CAPD group similar to HD. Treatment of calcium and phosphate disturbances, including vitamin D therapy, significantly reduces insulin resistance in uremia. Treatment with recombinant human erythropoietin (EPO) is an efficient way to increase hematocrit, to reverse cardiovascular problems and to improve insulin sensitivity. Angiotensin-converting enzyme inhibitors have been shown to improve insulin resistance, hyperinsulinemia and glucose intolerance in uremic patients. Thiazolidinediones (TZDs), the new insulin-sensitizing drugs, provide the proof that pharmacologic treatment of insulin resistance can be of enormous clinical benefit. The great potential of insulin resistance therapy illuminated by the TZDs will continue to catalyze research in this area directed toward the discovery of new insulin-sensitizing agents that work through other mechanisms.
Effect of Hollow Fiber Length on Solute Removal and Quantification of Internal Filtration Rate by Doppler Ultrasound
Authors: Sato Y. , Mineshima M. , Ishimori I. , Kaneko I. , Akiba T. , Teraoka S.
Published: January 2018

Renal replacement therapy with dialyzers capable of enhanced internal filtration (IF) can be an alternative to standard hemodiafiltration, as it provides convective solute removal comparable to that of hemodiafiltration by a simple procedure. In this study, we clinically evaluated the effect of the hollow fiber length in the dialyzer, a crucial factor influencing the rate of IF, by comparing two commercial dialyzers (BS-1.6U, BS-1.6UL, Toray, Japan) which differed in the fiber length, but had the same surface area and inner diameter of their hollow fibers. We showed that in the dialyzer with the longer fibers, the pressure profile along the dialyzer was significantly altered, and the solute clearance tended to be increased. In addition, we successfully quantified the IF rate with a Doppler ultrasound in the experimental circuit, by measuring the blood flow velocities along the bundle of fibers. We showed that the changes in the blood flow velocity were more marked in the dialyzer with the longer fibers; the calculated IF rates in the dialyzers with the shorter and longer fibers were 11.1 mL/min and 37.7 mL/min, respectively, which seemed to be compatible with the solute clearances. This simple and readily applicable method is expected to be useful in the development of modified dialyzers to fully exploit the benefits of IF in renal replacement therapy.
Modulation of Pro-apoptotic (Bax) and Anti-apoptotic (Bcl-2) Gene Expression in Isolated Porcine Hepatocytes Perfused within a Radial-flow Bioreactor after Low-temperature Storing
Authors: Mischiati C. , Puviani A. C. , Brogli M. , Guarniero S. , Sereni A. , Breda L. , Ricci D. , Galavotti D. , Morsiani E. , Gambari R.
Published: January 2018

Due to the scarcity of available human livers, porcine hepatocytes are currently being evaluated as a xenogeneic cell source for extracorporeal bioartificial liver (BAL). Hypothermic storage of isolated porcine hepatocytes could support stocking of cell-loaded bioreactors for BAL use and may provide bioreactors ready to be used at the patient's bedside. For the development of this technology, it is of utmost importance to ensure cell viability and differentiated functions after low-temperature storage and following warm reperfusion. We compared cell viability, functional activity and apoptosis in isolated porcine hepatocytes which were perfused within a radial-flow bioreactor (RFB), stored at 4°C and then reperfused at 37°C. RFBs were loaded with 8 × 109 ≥ 90% viable hepatocytes at 37°C for 3 h. RFBs were then flushed with 4° C University of Wisconsin solution (UW) and subsequently stored for 24 h or 48 h. RFBs were then reperfused for 8 h with recirculating medium plus serum at 37°C. Cytochrome P450 (CYP) activity was studied before and after cold storage by means of monoethylglycinexylide (MEGX) detection in the effluent medium, after repeated lidocaine injections. After reperfusion experiments, hepatocytes were harvested for total RNA isolation. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used in order to amplify specific mRNAs for Bcl-2 and Bax genes, by using appropriate primers; ß-actin primers were used as control. Total RNA was extracted by northern blotting analysis and for Bcl-2, Bax and ß-actin RNA messenger detection, RT-PCR amplification was used. Freshly isolated hepatocytes perfused into the RFB showed a progressive increase of MEGX while a loss in Bax expression was paralleled by an increase in Bcl-2 expression, in comparison to starting hepatocytes. After 4° C storage and warm reperfusion, MEGX production was preserved in 24 h- and 48 h-stored bioreactors as well as a sharp increase of Bcl-2 and a decrease of Bax mRNAs. Our study suggests that refrigeration of hepatocyte-bioreactors is a suitable strategy to maintain both viability and function of isolated hepatocytes, for up to 48 h a time-length that is compatible with long-distance delivery of ready-to-use bioreactors.
On-line Production of Ultrapure Substitution Fluid Reduces TNF-alpha- and IL-6 Release in Patients on Hemodiafiltration Therapy
Authors: Guth H.-J. , Gruska S. , Kraatz G.
Published: January 2018

On-line hemodiafiltration (HDF) has been introduced into clinical practice in the last few years. The most important technical and regulatory challenges were the safety and microbiological quality of ultrafiltrated substitution/replacement fluid. The application of ultrafilters in a different technical arrangement in the fluid path based on polysulfone or polyamide membranes should prevent patient contact with endotoxins and other pyrogenic or bacteria-derived substances. After resolving these problems and providing clinically safe and technically robust product solutions, increasing numbers of patients have been treated, especially those with severe clinical conditions, e.g., diabetes, hypo- or hypertension. The benefit for patients was brought about by the increase of substitution rate in hemodiafiltration and enhancing convective mass transfer. The impact of highly convective therapy modes on the state of immunomodulation towards the syndrome of microinflammation has not been investigated in a systematic prospective manner. In this study, 8 patients undergoing bag-HDF treatment with lactate buffered solution were investigated before online HDF treatment with commercially available whole blood stimulation assays testing for TNF-alpha and IL-6 release. Both assays are based on phytohemagglutinine (for TNF) and lipo-polysaccharide stimulation (for IL-6). Thereafter the patients were switched to on-line production of substitution fluid. After a wash-out period of 2 sessions the whole blood stimulation assays were applied to the same patients. The Wilcoxon test (for paired analysis) was done, revealing a statistically significant lower release of proinflammtory cytokines from patients' blood upon stimulation with PHA or LPS. The reduction of IL-6 and TNF concentration and release capacity in whole blood may be attributed to the use of high quality ultrapure substitution fluid and dialysate in on-line treatment instead of lactate buffer bag solution. These results indicate that not only an increase of convective mass tranfer by higher volume exchange, but also a decrease in unspecific activation of immunocompetent cells may have advantages for HDF-treated patients.
Radial Bone Mineral Density in Hemodialysis Patients with Adynamic Bone Disease
Authors: Nakashima A. , Yorioka N. , Doi S. , Ueda C. , Usui K. , Shigemoto K. , Harada S.
Published: January 2018

Adynamic bone disease (ABD) has attracted attention as the most frequent type of renal osteodystrophy, but there are few reports about the bone mineral density (BMD) in ABD patients. This study investigated the BMD in hemodialysis patients with ABD and with relatively normal bone turnover. We measured the BMD of the distal one-third of the radius by dual-energy X-ray adsorptiometry.

In the ABD group (intact PTH<65pg/ml, intact osteocalcin<30ng/ml), there were 19 men and 17 women with a mean age of 56.4±12.0 years. In the relatively normal bone turnover group (intact PTH: 120-250pg/ml), there were 24 men and 16 women with a mean age of 57.1±14.7 years. Although there were no significant differences between the two groups with respect to age, gender, and duration of hemodialysis, a significant increase of the BMD and the calcium x phosphate product was observed in the ABD group (radial BMD: 0.648±0.137 g/cm2 versus 0.572±0.132 g/cm2, calcium x phosphate product: 57.53±14.92 mg2/dl2 versus 49.76±12.13 mg2/dl2).

These findings suggest that an increase in radial BMD may not be a useful marker of the improvement in bone lesions in ABD patients.
Carboxyfluorescein Diacetate Succinimidyl Ester Facilitates Cell Tracing and Colocalization Studies in Bioartificial Organ Engineering
Authors: Mueller-Stahl K. , Kofidis T. , Akhyari P. , Wachsmann B. , Lenz A. , Boublik J. , Heine M. , Muehlfait V. , Haverich A. , Mertsching H.
Published: January 2018

Background

We demonstrate a method that includes colocalization studies to analyze cell suspensions after isolation and to characterize 3-dimensional grafts consisting of cells and matrix in vitro and in vivo.

Materials and methods

Neonatal rat cardiomyocytes were labelled by CFDA-SE after harvest. Cells in the isolated cell suspension, the embodied cells in the seeded scaffolds were characterized measuring features such as viability and distribution of the cell types.

Results

Selective cell count revealed high yields of viable cardiomyocytes. After seeding cells in collagen matrix, viability of the cells decreased gradually in the time process in vitro. Histology of implanted bioartificial myocardial tissue detected viable cardiomyocytes within the graft.

Conclusion

Using colocalization histology we could label and track cells within the bioartificial myocardial tissue graft in vitro and post implant and assess viability and distribution.
Collagen Expression in Tissue Engineered Cartilage of Aged Human Articular Chondrocytes in a Rotating Bioreactor
Authors: Marlovits S. , Tichy B. , Truppe M. , Gruber D. , Schlegel W.
Published: January 2018

This study describes the culture and three-dimensional assembly of aged human articular chondrocytes under controlled oxygenation and low shear stress in a rotating-wall vessel. Chondrocytes cultured in monolayer were released and placed without any scaffold as a single cell suspension in a rotating bioreactor for 12 weeks. Samples were analyzed with immunohistochemistry, molecular biology and electron microscopy. During serial monolayer cultures chondrocytes dedifferentiated to a “fibroblast-like” structure and produced predominantly collagen type I. When these dedifferentiated cells were transferred to the rotating bioreactor, the cells showed a spontaneous aggregation and formation of solid tissue during the culture time. Expression of collagen type II and other components critical for the extracellular cartilage matrix could be detected. Transmission electron microscopy revealed a fine network of randomly distributed collagen fibrils. This rotating bioreactor proves to be a useful tool for providing an environment that enables dedifferentiated chondrocytes to redifferentiate and produce a cartilage-specific extracellular matrix.
Application of Taylor Vortices in Hemocompatibility Investigations
Authors: Körfer S. , Klaus S. , Mottaghy K.
Published: January 2018

Background

Artificial organs, implants and extracorporeal circulation affect the physiological flow characteristics of blood as a liquid organ. These artificial systems consist of a wide variety of biomaterials with different geometries and, therefore, with their own flow properties. Secondary flow also occurs in extra – as well as in intracorporeal circulation.

Methods

In order to investigate the influence of vortical flow conditions a modified Taylor-Couette system was introduced. It consisted of two coaxial cylinders whose surfaces were the target of investigation. The annular gap was filled with donor blood shear and secondary flows were produced by rotating the inner cylinder. Platelet activation and protein adsorption were investigated as markers for thrombogenicity.

Results

At shear rates high enough to establish stable Taylor vortices (G ≥ 550 s −1) significant differences between vortical Taylor flow and steady laminar flow were detected. At shear rates of G ≥ 550 s −1 laminar flow caused a significantly higher platelet drop and PF4 release when compared to Taylor vortex flow. Also protein adsorption per square unit was significantly higher for laminar flow.

Conclusions

Based on the present data we conclude that vortical flow patterns lead to an accumulation of platelets and plasma proteins in the vortex center and therefore to a decreased probability of contact between platelets and material surfaces. It can be concluded that a preactivation of the platelets circulating in extracorporeal circuits can be manifested downstream in other geometrical configurations and flow conditions.
Treatment Strategies for Postinfarction Left Ventricular Free Wall Rupture: Stabilization with Peri-operative IABP and off-pump Repair
Authors: Nappi G. , De Santo L. S. , Torella M. , Della Corte A. , Maresca L. , Romano G. , Cotrufo M.
Published: January 2018

Background

Perioperative management of post-infarction left ventricular free wall rupture (LVFWR) is not clearly standardized and surgical repair is the only therapeutic option. Role of off-pump surgery and stabilization with perioperative intraaortic balloon pumping (IABP) were here analysed.

Methods

Seven patients underwent surgery for LVFWR between 1990 and 2002. Clinical picture included electromechanical dissociation (3 patients) and sudden hypotension (4 patients). Except in one patient who was reanimated through femoro-femoral cardiopulmonary bypass, off-pump repair through on-lay patching technique was always performed. IABP was employed in the immediate postoperative period in five cases.

Results

A satisfactory hemodynamic state was restored in all cases and there were no reoperations for bleeding or rerupture. Hospital survival was 100%. One patient underwent successful surgical myocardial revascularization two months after LVFWR. Two patients died at follow-up. The survivors present with good NYHA and CCS functional classes.

Conclusions

When the anatomy of the LVFWR is favourable, off-pump external patching repair proves a good choice. Postoperative IABP provides satisfactory hemodynamic support.
Recovery of Organ Dysfunction during Bridging to Heart Transplantation in Children and Adolescents
Authors: Reiss N. , Ei-Banayosy A. , Arusoglu L. , Kleikamp G. , Minami K. , Körfer R.
Published: January 2018

The beneficial effects of ventricular assist devices on organ dysfunction during bridging to heart transplantation have been widely reported in the adult population. In contrast, the use of ventricular assist devices used as bridge-to-transplant in children is limited. To evaluate organ recovery during ventricular support in pediatric transplant candidate, respiratory, renal and hepatic function were reviewed retrospectively.

The Thoratec device (stroke volume 65 ml) and the HIA-Medos-system (stroke volume 25/10 ml) were used as bridge-to transplant in 11 children and adolescents who were in low-output-syndrome despite maximal pharmacological support.

Prior to implantation five patients were mechanically ventilated, six patients underwent cardiopulmonary resuscitation, eight patients had anuria (one treated by hemofiltration), three patients had liver dysfunction and four patients had signs of severe infection. At the time of implantation one patient was supported by the intraaortic balloon pump and one by the femorofemoral bypass for rapid hemodynamic stabilization.

Eight patients were treated using the Thoratec device (one of these by Nova cor on the left side), three by the HIA-Medos system. The support time ranged between seven and 140 days.

Seven patients could be extubated within three days. Renal function recovered in all pts. Liver enzymes decreased in all pts without reaching normal values. Bilirubin values also decreased in survivors but increased to 9.3 mg/dL in non-survivors. At least seven patients underwent successful heart transplantation, three patients died because of multiorgan failure after extended transfusion and one patient because of technical failure.

In our experience the hemodynamic situation was sufficient in all bridging to transplant candidates. In all patients who underwent successful transplantation, transplantability was associated with rapid organ recovery within seven days after initiating mechanical assistance. Extended blood tranfusions, combined failure of three organs and increasing bilirubin values during support seem to be predictors of poor outcome.
Development of Cone and Plate-Type Rheometer for Quantitative Analysis of Endothelial Cell Detachment by Shear Stress
Authors: Furukawa K.S. , Ushida T. , Noguchi T. , Tamaki T. , Tateishi T.
Published: January 2018

We developed an apparatus, which has a structure based on a cone and plate-type rheometer, to facilitate quantitative analysis of the detachment process of endothelial cells (EC) from diverse materials including 3-dimensional scaffolds such as plate, membrane and porous-shaped materials. As an artificial vascular model, a material inoculated with EC to a polycarbonate membrane coated with laminin was prepared. In consequence, reduced cell number, medium volume, and material size was enough to evaluate cell detachment from various materials by shear stress in our system. When shear stress was loaded to a material with EC, the ratio retained of initially inoculated cells decreased with time. Increase of magnitude of shear stress also decreased the ratio. We conclude that our apparatus could analyze quantitatively detachment of EC with ease for screenings to find materials that enhance adhesive force of EC. To produce artificial blood vessels with small diameter, our apparatus could become a useful instrument.
Twenty Years of Renal Replacement Therapy in a Type 1 Diabetic Patient: Advantages of a Multiple Choice Dialysis System
Authors: Piccoli G.B. , Mesiano P. , Mezza E. , Pacitti A. , Burdese M. , Bermond F. , Jeantet A. , Segoloni G.P.
Published: January 2018

The prognosis of diabetic patients on renal replacement therapy (RRT) is usually poor. We report on the type 1 diabetic woman with the longest RRT follow-up in our area: over 20 years, half on dialysis, half with a renal graft. CS started RRT at age 27 on peritoneal dialysis (3 years), continued until an underdialysis syndrome developed, was switched to acetate dialysis and, because of poor tolerance, to hemofiltration which with good clinical results, allowing her to become the first Italian patient on home hemofiltration, which continued for 5 years. A cadaver graft lasted for the subsequent decade, despite several complications; afterwards she resumed bicarbonate dialysis, choosing a frequent home hemodialysis schedule. Despite several vascular access problems, her clinical conditions were good enough to candidate her for a second renal transplant, performed 3 years ago. This history of active self-care may draw attention to the advantages of a multiple choice dialysis network.
ß2-Microglobulin Clearance with Super High Flux Hemodialysis: an Ex Vivo Study
Authors: Lee W.C.R. , Uchino S. , Fealy N. , Baldwin I. , Panagiotopoulos S. , Goehl H. , Morgera S. , Neumayer H.-H. , Bellomo R.
Published: January 2018

Background

ß2m accumulation induces disease in patients with end-stage renal failure (ESRF). Thus, its removal from patients with ESRF appears desirable. Current dialysis technology, however, has limited effectiveness.

Aims

To measure ß2m clearance with a novel super high flux membrane.

Design

Ex vivo experimental study.

Setting

Intensive Care Laboratory of Tertiary institution.

Subjects

Six volunteers.

Measurements and Results

At a blood flow of 300 ml/min, the clearance of ß2-MG increased from 113.5 ± 38.5 ml/min with a dialysate flow rate of 200 ml/min to 184.8 ± 61.1 ml/min with a flow rate of 300 ml/min and 195.0 ± 60.0 ml/min with a 500 ml/min flow rate. The clearance of albumin was 4.5 ml/min with a dialysate flow rate of 200 ml/min, 5.2 ml/min for a flow rate of 300 ml/min and 5.8 ml/min for a flow rate of 500 ml/min.

Conclusions

High levels of ß2m clearance can be achieved with a super high flux membrane while albumin losses remain limited
In Vitro Biocompatibility of Titanium Oxide for Prosthetic Devices Nanostructured by Low Pressure Metal-Organic Chemical Vapor Deposition
Authors: Giavaresi G. , Giardino R. , Ambrosio L. , Battiston G. , Gerbasi R. , Fini M. , Rimondini L. , Torricelli P.
Published: January 2018

Metal-Organic Chemical Vapor Deposition (MOCVD) has recently been proposed to coat orthopedic and dental prostheses with metal nanostructured oxide films through the decomposition of oxygenated compounds (single-source precursors) or the reaction of oxygen-free metal compounds with oxygenating agents. The present study was carried out to assess the in vitro biocompatibility in terms of cell proliferation and activation, of commercially pure Ti (control material: TI/MA) coated with nanostructured TiO2 film by MOCVD (Ti/MOCVD) using osteoblast-like cell cultures (MG-63). Evaluations were performed at 3, 7 and 14 days. Cell proliferation showed a similar trend for Ti/MA and Ti/MOCVD compared to polystyrene; cell number increased with time from seeding to day 7 (p < 0.005), and then decreased progressively until day 14 (ranging from −14% to −47%). The ALP level and OC production showed no significant differences between Ti/MOCVD and Ti/MA at each experimental time. Significantly higher ALP levels were found in Ti/MA at 3 days and in Ti/MOCVD at 7 and 14 days when compared to the polystyrene group. OC production decreased over time and the highest values were observed at 3 days, when it was significantly higher in the Ti/MA than in the polystyrene group (50%, p < 0.05). CICP synthesis was positively affected by the presence of Ti/MOCVD and was higher in Ti/MOCVD than in the polystyrene group. No significant differences were found between Ti/MOCVD and Ti/MA in terms of IL-6 and TGF-ß1 synthesis at any experimental time. In conclusion, the current findings demonstrate that the nanostructured TiO2 coating positively affects the osteoblast-like cell behavior in terms of cell proliferation and activity, thus confirming its high level of in vitro biocompatibility in accordance with expectations.
A Chronic Heart Failure Model by Coronary Artery Ligation in the Goat
Authors: Kim W.G. , Cho S.R. , Sung S.H. , Park H.J.
Published: January 2018

The availability of a reliable heart failure model in large animals is important. We report upon our efforts to develop a chronic heart failure model in seven goats using sequential ligation of the left anterior descending (LAD) coronary artery and its diagonal branch. After anesthesia and left thoracotomy, the LAD artery was ligated, and the diagonal vessel at the same level was ligated one hour later. Cardiac measurements were performed with a thermodilution catheter and by ultrasonography. Two months after the operation, the same measurements were made and animals were sacrificed for postmortem examinations of their hearts. Hemodynamic measurements, except cardiac output, showed no significant changes immediately after the coronary artery ligation. Echocardiographic measurements showed significant changes in the ejection fraction and fractional shortening without changes in left ventricular dimensions. Wall motion analyses demonstrated variable degrees of anteroseptal dyskinesia and akinesia in all animals immediately after coronary artery ligation. Five animals have undergone hemodynamic and ultrasonographic studies 2 months after coronary artery ligation. The results obtained from these animals showed significant increases in central venous pressure, right ventricular pressure, pulmonary artery pressure, and pulmonary artery capillary wedge pressure, and a significant decrease in cardiac output. Increases in left ventricular dimensions and decreases in ejection fraction with fractional shortening in ultrasonographic studies were also observed. Pathologically, well-demarcated thin-walled anteroseptal infarcts, with chamber enlargement, were clearly seen with dilatation of the heart chambers in all specimens. Based on this study, we conclude that goats, like sheep, can provide a reliable model of chronic heart failure by coronary artery ligation and in view of the many advantages offered by goats, we believe that this animal model will be useful for cardiac experimentation.
Numerical Simulation of a Realistic Total Cavo-pulmonary Connection: Effect of Unbalanced Pulmonary Resistances on Hydrodynamic Performance
Authors: Grigioni M. , Daniele C. , Del Gaudio C. , Morbiducci U. , Balducci A. , D'avenio G. , Amodeo A. , Barbaro V. , Di Donato R.
Published: January 2018

Total cavo pulmonary connection (TCPC) is one of the surgical techniques adopted to compensate the failure of the right heart in pediatric patients. The main goal of this procedure is the realization of a configuration for the caval veins and for the pulmonary arteries that can guarantee as low as possible pressure losses and appropriate lung perfusion. Starting from this point of view, a realistic TCPC with extracardiac conduit (TECPC) is investigated by means of Computational Fluid Dynamics (CFD) to evaluate the pressure loss under different pressure conditions, simulating different vessel resistances, on the pulmonary arteries. A total flow of 3 L/min, with a distribution between the inferior vena cava (IVC) and the superior vena cava (SVC) equal to 6/4, was investigated; three different boundary conditions for the pressure were imposed, resulting in three simulations in steady-state conditions, to the right pulmonary artery (RPA) and to the left pulmonary artery (LPA), simulating a balanced (ΔPLPA-RPA=0 mmHg) and two unbalanced pulmonary resistances to blood flow (a pressure difference ΔPLPA-RPA = ±2 mmHg, respectively). The geometry for the TECPC was realized according to MRI derived physiological values for the vessels and for the configuration adopted for the anastomosis (the extra-cardiac conduit was inclined 22° towards the left pulmonary artery with respect to the IVC axis). The computed power losses agree with previous in vitro Particle Image Velocimetry investigations. The results show that a higher resistance on the LPA causes the greater pressure loss for the TECPC under study, while the minimum pressure loss can be achieved balancing the pulmonary resistances, subsequently obtaining a balanced flow repartition towards the lungs.
Pilot Study on Prevention of Lung Injury during Surgery for Type a Acute Aortic Dissection: No Evident Improvements with Celsior Flushing through the Pulmonary Artery
Authors: De Santo L.S. , Romano G. , Amarelli C. , Corte A. Della , Onorati F. , Torella M. , De Feo M. , Nappi G.A. , Cotrufo M.
Published: January 2018

Objective

Postoperative respiratory failure is a frequent and serious complication in patients with type A acute aortic dissection. Experimental evidence suggests that pulmonary artery perfusion using hypothermic protective solutions helps prevent lung injury. The aim of this pilot prospective study was to evaluate the effect of pulmonary artery flushing during selective cerebral perfusion (SCP) on lung function.

Methods

Twenty patients referred for acute type A aortic dissection, who were free from preoperative respiratory dysfunction, were assigned prospectively and alternately to two treatment groups. Pulmonary flushing was performed during SCP in group P (10 patients), while conventional Kazui technique was applied in group N (10 patients). Lung perfusion consisted of single-shot hypothermic pulmonary artery flush with Celsior. Lung function was evaluated by intubation time, scoring of chest radiograms at 12 hours after CPB, and PaO2/FiO2 assessed from immediately before surgery to 72 hours after termination of cardiopulmonary bypass.

Results

Incidence of pre, intra and post operative determinants of lung dysfunction proved homogeneous in both groups. Lung oxygenation function showed a marked post operative decline followed by a slow improvement in both groups. Analysis of respiratory ratios did not disclose significant differences even though the flushed group had a better performance in all study patients. The incidence of prolonged ventilator support (longer than 72 hours) (30% vs 20%, p=NS) and severity of x-ray pulmonary infiltrate score were comparable (mean score 1.7±0.71 vs 1.6±0.68, p=NS).

Conclusions

Pulmonary artery flushing with Celsior solution does not seem to provide an effective preservation of lung function.