Functionalization of TiO2 sol-gel derived films for cell confinement.

The neuroscience field has increased enormously over the last decades, achieving the possible real application of neuronal cultures not only for reproducing neural architectures resembling in vivo tissues, but also for the development of functional devices. In this context, surface patterning for cell confinement is crucial, and new active materials together with new protocols for preparing substrates suitable for confining cells, guiding their processes in the desired configuration are extremely appreciated. Here, TiO2 sol-gel derived films were selected as proof-of-concept materials to grow neurons in suitable confined configurations, taking advantage of the biocompatible properties of modified TiO2 substrates. TiO2 sol-gel derived films were made compatible with the growth of neurons thanks to a stable and controlled poly-lysine coating, obtained by silanization chemistry and streptavidin-biotin interactions. Moreover, a spotting protocol, here described and optimized, allowed the simple preparation of arrays of neurons, where cell adhesion was guided in specific areas and the neurites development driven in the desired arrangement. The resulting arrays were successfully tested for the growth and differentiation of neurons, demonstrating the possible adhesion of cells in specific areas of the film, therefore paving the way to applications such as the direct growth of excitable cells nearby electrodes of devices, with an evident enhancement of cell-electrodes communication.

Prototyping a memristive-based device to analyze neuronal excitability.

Many efforts have been spent in the last decade for the development of nanoscale synaptic devices integrated into neuromorphic circuits, trying to emulate the behavior of natural synapses. The study of brain properties with the standard approaches based on biocompatible electrodes coupled to conventional electronics, however, presents strong limitations, which in turn could be overcame by the in-situ growth of neuronal networks coupled to memristive devices. To meet this challenging task, here two different chips were designed and fabricated for culturing neuronal cells and sensing their electrophysiological activity. The first chip was designed to be connected to an external memristor, while the second chip was coated with TiO2 films owning memristive properties. The biocompatibility of chips was preliminary analyzed by culturing the hybrid motor-neuron cell line NSC-34 and by measuring the electrical activity of cells interfacing the chip with a standard patch-clamp setup. Next, neurons were seeded on chips and their activity measured with the same setup. For both cell types total current and voltage responses were evoked and recorded with optimal results with no breakdowns. In addition, an external stimulation was applied to cells through chip electrodes, being effective and causing no damage or pitfalls to the cells. Finally, the whole bio-hybrid system, i.e. the chip interconnected with a commercial memristor, was tested with promising results. Spontaneous electrical activity of neurons grown on the chip was indeed present and this signal was collected and sent to the memristor, changing its state. Taken together, we demonstrated the ability of memristor to work with a synaptic/plastic response together with natural systems, opening the way for the further implementation of basic computing elements able to perform both storage and processing of data, as in natural neurons.

A new silanizing agent tailored to surface bio-functionalization.

Amino-terminated surfaces can be effectively obtained by means of silanizing agents, realizing surfaces suitable for the purification of biomarkers of several pathologies. Since the level of biomarkers, such as microRNAs and cell-free DNA, into circulation may be extremely low, new and ameliorated capturing molecules and protocols are highly required. In this work, a new silane, acetone-imine propyl trimethoxysilane (AIPTMS), is synthesized with a simple and elegant reaction, via the nucleophilic addition of the primary amino group to the carbonyl group of acetone. AIPTMS and APTMS were used to silanize silicon oxide surfaces, which were characterized chemically (XPS) and morphologically (AFM). The two types of surfaces were chemically similar, but behaved very differently both for surface morphology and functional properties. The AIPTMS-modified surface was indeed very smooth and homogeneous with respect to the APTMS-modified surface. Moreover, the AIPTMS surface captured larger amounts of nucleic acids almost immediately after preparation, while APTMS-based functional surfaces needed longer time to reach comparable efficiency. AIPTMS shows several advantages over standard aminosilanes, as it realizes a more homogeneous surface coverage that, in turn, produces an improved response towards the capture of nucleic acids. AIPTMS is a very promising reagent for the reliable and reproducible preparation of active biofunctional surfaces for the purification and analysis of circulating biomarkers.

Simple PDMS microdevice for biomedical applications.

Polydimethylsiloxane (PDMS) is a well-known biocompatible polymer employed for many applications in the biomedical field. In this study, the biocompatibility and versatility of PDMS was tested setting up a microdevice devoted to the purification and analysis of nucleic acids. The PDMS microdevice was demonstrated to successfully fulfill all requirements of genetic analyses such as genotyping and pathogen DNA identification both in multiplex and real-time PCR, suggesting the possibility to carry out a molecular test directly on-chip. Moreover, the PDMS microdevice was successfully applied to the purification and detection of disease biomarkers, such as microRNAs related to cancer or heart disease. On-chip microRNA purification was demonstrated starting from clinically relevant samples, i.e. plasma, serum, tissue biopsies. Significantly, the purification and the transcription of microRNA into cDNA occur in the same PDMS chamber, saving time and labor for the overall analysis. Again, the PDMS microdevice was confirmed as a notable candidate for compact, rapid, easy-to-use molecular tests.

Fatigue and biological properties of Ti-6Al-4V ELI cellular structures with variously arranged cubic cells made by selective laser melting.

Traditional implants made of bulk titanium are much stiffer than human bone and this mismatch can induce stress shielding. Although more complex to produce and with less predictable properties compared to bulk implants, implants with a highly porous structure can be produced to match the bone stiffness and at the same time favor bone ingrowth and regeneration. This paper presents the results of the mechanical and dimensional characterization of different regular cubic open-cell cellular structures produced by Selective Laser Melting (SLM) of Ti6Al4V alloy, all with the same nominal elastic modulus of 3GPa that matches that of human trabecular bone. The main objective of this research was to determine which structure has the best fatigue resistance through fully reversed fatigue tests on cellular specimens. The quality of the manufacturing process and the discrepancy between the actual measured cell parameters and the nominal CAD values were assessed through an extensive metrological analysis. The results of the metrological assessment allowed us to discuss the effect of manufacturing defects (porosity, surface roughness and geometrical inaccuracies) on the mechanical properties. Half of the specimens was subjected to a stress relief thermal treatment while the other half to Hot Isostatic Pressing (HIP), and we compared the effect of the treatments on porosity and on the mechanical properties. Fatigue strength seems to be highly dependent on the surface irregularities and notches introduced during the manufacturing process. In fully reversed fatigue tests, the high performances of stretching dominated structures compared to bending dominated structures are not found. In fact, with thicker struts, such structures proved to be more resistant, even if bending actions were present.

Cell transfer of information via miR-loaded exosomes: a biophysical approach.

A new communication route among cells was reported in recent years, via extracellular vesicles and their cargo. Exosomes in particular are attracting increasing interest as privileged mediators of this cell communication route. The exosome-mediated transfer of nucleic acids, especially of microRNAs, is particularly promising for their use both as biomarkers of pathologies and as a therapeutic tool. Here, a simplified model of interaction among cells, microRNAs and vesicles is studied using a biophysical approach. A synthetic and fluorescent microRNA (i.e. miR-1246 conjugated with TAMRA) was selected to model cell communication, monitoring its internalization in cells. The fluorescent miR-1246, either naked or included in synthetic or natural vesicles, was incubated with human breast adenocarcinoma cells (MCF7) for different times. A comparison between this human microRNA and its DNA copy or an exogenous microRNA (from Caenorhabditis elegans) allowed assessment of the specificity of the information transfer through microRNAs, and especially associated with exosomes. The uptake of naked miR-1246 was indeed higher both in terms of number of targeted cells and intensity of fluorescence signal with respect to the other nucleic acids tested. The same occurred with miR-1246 loaded exosomes, evidencing a specific uptake only partially due to the lipidic components and present only when the human microRNA was loaded in exosomes, which were themselves derived from the same MCF7 cells.

miRNA purification with an optimized PDMS microdevice: Toward the direct purification of low abundant circulating biomarkers.

A reliable clinical assay based on circulating microRNAs (miRNAs) as biomarkers is highly required. Microdevices offer an attractive solution as a fast and inexpensive way of concentrating these biomarkers from a low sample volume. A previously developed polydimethylsiloxane (PDMS) microdevice able to purify and detect circulating miRNAs was here optimized. The optimization of the morphological and chemical surface properties by nanopatterning and functionalization is presented. Surfaces were firstly characterized by atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), fluorescamine assay and s-SDTB (sulphosuccinimidyl-4-o-(4,4-dimethoxytrityl) butyrate) assay and subsequently tested for their capacity to adsorb a fluorescent miRNA. From our analysis, modification of surface charge with 0.1% APTMS ((3-Aminopropyl)trimethoxysilane) and 0.9% PEG-s (2-[Methoxy-(polyethyleneoxy)propyl]trimethoxysilane) performed at 60°C for 10min was identified as the best purification condition. Our optimized microdevice integrated with real-time PCR detection, was demonstrated to selectively purify both synthetic and natural circulating miRNAs with a sensitivity of 0.01pM.

The effect of post-sintering treatments on the fatigue and biological behavior of Ti-6Al-4V ELI parts made by selective laser melting.

Fatigue resistance and biocompatibility are key parameters for the successful implantation of hard-tissue prostheses, which nowadays are more and more frequently manufactured by selective laser melting (SLM). For this purpose, the present paper is aimed at investigating the effect of post-sintering treatments on the fatigue behavior and biological properties of Ti samples produced by SLM. After the building process, all samples are heat treated to achieve a complete stress relief. The remaining ones are tribofinished with the aim of reducing the surface roughness of the as-sintered condition. Part of the tribofinished samples are then subjected to one of the following post-sintering treatments: (i) shot peening, (ii) hot isostatic pressing (HIP), and (iii) electropolishing. It is found that shot peening and HIP are the most effective treatments to improve the high and the very-high cycle fatigue resistance, respectively. At the same time, they preserve the good biocompatibility ensured by the biomedical Titanium Grade 23.

Bio-functional surfaces for the immunocapture of AGO2-bound microRNAs.

MicroRNAs (miRNAs) are endogenous, small (18-24nt), non-coding RNAs that regulate gene expression. Among miRNAs, those bound to the AGO2 protein are the functionally active fraction which mediates the cell regulatory processes and regulate messages exchanged by cells. Several methods have been developed to purify this fraction of microRNAs, such as immunoprecipitation and immunoprecipitation-derived techniques. However, all these techniques are generally recognized as technically complicated and time consuming. Here, a new bio-functional surface for the specific capture of AGO2-bound microRNAs is proposed. Starting from a silicon oxide surface, a protein A layer was covalently bound via epoxy chemistry to orient specific anti-AGO2 antibodies on the surface. The anti-AGO2 antibodies captured the AGO2 protein present in cell lysate and in human plasma. The AGO2-bound microRNAs were then released by enzymatic digestion and detected via RT-qPCR. Control surfaces were also prepared and tested. Every step in the preparation of the bio-functional surfaces was fully characterized from the chemical, morphological and functional point of view. The resulting bio-functional surface is able to specifically capture the AGO2-bound miRNAs from biologically-relevant samples, such as cell lysate and human plasma. These samples contain different proportions of AGO2-bound microRNAs, as reliably detected with the immunocapture method here proposed. This work opens new perspectives for a simple and faster method to isolate not only AGO2-bound microRNAs, but also the multiprotein complex containing AGO2 and miRNAs.

Smart detection of microRNAs through fluorescence enhancement on a photonic crystal.

The detection of low abundant biomarkers, such as circulating microRNAs, demands innovative detection methods with increased resolution, sensitivity and specificity. Here, a biofunctional surface was implemented for the selective capture of microRNAs, which were detected through fluorescence enhancement directly on a photonic crystal. To set up the optimal biofunctional surface, epoxy-coated commercially available microscope slides were spotted with specific anti-microRNA probes. The optimal concentration of probe as well as of passivating agent were selected and employed for titrating the microRNA hybridization. Cross-hybridization of different microRNAs was also tested, resulting negligible. Once optimized, the protocol was adapted to the photonic crystal surface, where fluorescent synthetic miR-16 was hybridized and imaged with a dedicated equipment. The photonic crystal consists of a dielectric multilayer patterned with a grating structure. In this way, it is possible to take advantage from both a resonant excitation of fluorophores and an angularly redirection of the emitted radiation. As a result, a significant fluorescence enhancement due to the resonant structure is collected from the patterned photonic crystal with respect to the outer non-structured surface. The dedicated read-out system is compact and based on a wide-field imaging detection, with little or no optical alignment issues, which makes this approach particularly interesting for further development such as for example in microarray-type bioassays.

On-chip purification and detection of hepatitis C virus RNA from human plasma.

Hepatitis C virus (HCV) is one of the main causes of chronic liver disease worldwide. The diagnosis and monitoring of HCV infection is a crucial need in the clinical management. The conventional diagnostic technologies are challenged when trying to address molecular diagnostics, especially because they require a complex and time-consuming sample preparation phase. Here, a new concept based on surface functionalization was applied to viral RNA purification: first of all polydimethylsiloxane (PDMS) flat surfaces were modified to hold RNA adsorption. After a careful chemical and morphological analysis of the modified surfaces, the functionalization protocols giving the best RNA adsorbing surfaces were applied to PDMS microdevices. The functionalized microdevices were then used for RNA purification from HCV infected human plasma samples. RNA purification and RT were successfully performed in the same microdevice chamber, saving time of analysis, reagents, and labor. The PCR protocol for HCV cDNA amplification was also implemented in the microdevice, demonstrating that the entire process of HCV analysis, from plasma to molecular readout, could be performed on-chip. Not only HCV but also other microdevice-based viral RNA detection could therefore result in a successful Point-of-Care (POC) diagnostics for resource-limited settings.

Enhanced fluorescence detection of miRNA-16 on a photonic crystal.

We report a novel sensing method for fluorescence-labelled microRNAs (miRNAs) spotted on an all-dielectric photonic structure. Such a photonic structure provides an enhanced excitation and a directional beaming of the emitted fluorescence, resulting in a significant improvement of the overall signal collected. As a result, the Limit of Detection (LoD) is demonstrated to decrease by a factor of about 50. A compact read-out system allows a wide-field imaging-based detection, with little or no optical alignment issues, which makes this approach particularly interesting for further development for example in microarray-type bioassays.

Innovative microRNA purification based on surface properties modulation.

The increasing interest in circulating microRNAs (miRNAs) as potential non-invasive cancer biomarkers has prompted the rapid development of several extraction techniques. However, current methods lack standardization and are costly and labor intensive. In light of this, we developed a microRNA solid-phase extraction strategy based on charge and roughness modulation on substrate surfaces. PECVD treated silicon oxide (PECVD-SO) and thermally grown silicon oxide (TG-SO) surfaces were functionalized with positively charged 3-aminopropyltriethoxysilanes (APTES) and neutral poly(ethylene glycol) silanes (PEG-s) mixed in different proportions to modulate the density of net positive charges and the roughness of the substrate. Characterization of the surfaces was performed by atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and s-SDTB (sulfosuccinimidyl-4-o-(4,4-dimethoxytrityl) butyrate) assay in order to investigate the surface morphology and chemical composition, respectively. Adsorption and elution efficiency were assessed by fluorescence microscopy by means of synthetic fluorescently labeled microRNAs. We identified PECVD-SO functionalized with 0.1% APTES and 0.9% 21-24 units long PEG-s as a promising surface able to selectively bind microRNAs and release them in the presence of a basic buffer (pH=9) compatible with downstream analyses. MicroRNA integrity was assessed by reverse transcription and real-time PCR and confirmed by electrophoresis (Agilent 2100 Bioanalyzer), while binding competition from circulating DNA and proteins was excluded by fluorescence analyses and real-time PCR. On the contrary, total RNA slightly decreased miRNA adsorption. In conclusion, we showed an innovative and easy solid-state purification method for circulating miRNAs based on charge interaction, which could pave the path to future diagnostic and prognostic assays feasible as a routine test.

One-shot genetic analysis in monolithic Silicon/Pyrex microdevices.

Modern Lab-on-a-chip (LOC) platforms for genomic applications integrate several biological tasks in a single device. Combination of these processes into a single device minimizes sample loss and contamination problems as well as reducing analysis time and costs. Here we present a study of a microchip platform aimed at analyzing issues arising from the combination of different functions, such as DNA purification from blood, target amplification by PCR and DNA detection in a single silicon-based device. DNA purification is realized through two different strategies: 1) amine groups coating microchannel surfaces and 2) magnetic nanoparticles coated by chitosan. In the first strategy silicon/Pyrex microdevices coated with 3-aminopropyltriethoxysilane (APTES) or 3-2-(2-aminoethylamino)-ethylamino]-propyltrimethoxysilane (AEEA) were examined and their efficiency in human genomic DNA adsorption/desorption was evaluated. APTES treatment was the most suitable for the purification of a reasonable amount of DNA in a state suitable for the following PCR step. The second strategy has instead the main advantage of avoiding an elution step, since the DNA adsorbed on the magnetic nanoparticles can be used as PCR template. On-chip PCR was performed in a custom thermocycler, while the detection of PCR products was carried out by fluorescence reading. A complete genetic analysis was demonstrated on the monolithic silicon/Pyrex microchip, starting from less than 1 [Formula: see text]L of human whole blood and arriving at SNPs identification. The successful integration of DNA purification, amplification and detection on a single microdevice was proven without the need for biological passivation steps and possibly simplifying the realization of genomic detection devices.

Vapor-phase self-assembled monolayers of aminosilane on plasma-activated silicon substrates.

Aminosilane self-assembled monolayers on silicon substrates have been prepared via a gas-phase procedure based on the consecutive reactions of the aminosilane precursor and water vapor. X-ray photoelectron spectroscopy, atomic force microscopy, and contact angle measurements have been used to characterize the aminosilane layers. For comparison, substrates modified with aminosilane through a liquid-phase procedure have been prepared and characterized by means of the same techniques. The vapor-based procedure was found to yield more uniform layers characterized by fewer and smaller aggregates as compared with liquid-treated substrates. Grazing angles reflection Fourier transform infrared measurements were carried out on the vapor-treated substrates before and after water exposure to investigate the hydrolysis of the alkoxy groups and further reaction to form siloxane bonds. The surface density of amino groups, as estimated through a colorimetric method, is very similar for vapor- and liquid-treated substrates, suggesting a similar reactivity and accessibility of the functional groups on the surface.

Immobilization of cationic rifampicin-loaded liposomes on polystyrene for drug-delivery applications.

Polymer-associated infections are a major problem in implanted or intravascular devices. Among others, microorganisms of the staphylococcal family have been identified as the most important culprit. Prevention of bacterial adhesion and colonization of polymeric surfaces by release of antimicrobial agents incorporated into the polymers itself are currently under study. We have developed a novel method for the functionalization of a polymeric surface which is based on the deposition of covalently coupled lipid structures from antibiotic loaded vesicles. We have found that such process significantly reduces the bacterial growth on polystyrene material. In this work, lipid coverage obtained from multilamellar (MLVs) and extruded unilamellar (LUVs) vesicles were analyzed with respect to their adhesion efficiency on three types of polystyrene (PS) well-plates. Two methods of lipid deposition were characterized and compared in terms of surface lipid density and time stability: deposition of cationic vesicles on negatively charged surfaces and formation of covalent linkages between functionalized lipids and amines enriched surfaces. In order to study the antibiotic encapsulation efficiency we measured how the rifampicin (RIF) loading was affected by changes of liposome charge upon introduction of various amounts of stearylamine (SA), distearoyl-trimethylammonium propane (DSTAP) or dioleoyloxypropyl-trimethylammonium chloride (DOTAP) into the liposomal formulation. RIF-coated polymeric surfaces were also tested against a Staphylococcus epidermidis strain to evaluate their efficacy in vitro, showing that only approximately 2% of such bacteria inoculated on MLV-treated PS substrate were able to proliferate. Covalently immobilized lipid films showed about a tenfold increase in time stability compared to electrostatically bonded lipid films. Furthermore, substrates covalently modified with RIF-loaded MLVs retained an antibacterial activity for up to 12 days when aged in buffer at 37 degrees C. Such antimicrobial polymer coatings show promise for their use as antibacterial barrier for the prevention of catheter-related infections.

Role of chemical interactions in bacterial adhesion to polymer surfaces.

Development of biomaterial-related infections is attracting an increasing interest due to the significant percentage of implant failure in the hospital care. Recent literature puts in evidence the dependence of the infection risk on the different biomaterials used, because of the different interactions between material surface and micro-organisms. Despite this, the mechanisms underlying the adhesion of bacteria to the biomaterial surface are still unclear. Aim of this work is to study the initial events of the processes responsible for the bacterial adhesion on polymers in order to prevent the development of bacterial infections and the consequent failure and replacement of biomedical devices. Electrostatic and Lifshitz-van der Waals forces are usually considered responsible for the interactions at the biomaterial interface. A new term that involves Lewis acid-base interactions is here introduced to better describe the bacterial adhesion to the polymer surface. Two requirements are needed to test this hypothesis: the development of an ideal polymeric surface in terms of chemical and morphological properties and the choice of a specific bacterial strain to be utilized as "probe". Experiments were worked out using an Escherichia coli (Gram-) strain that represent one of the principal isolates from infected biomaterial implants and its adhesion was investigated on polymers having different acid/basic character. The findings indicate that the bacterial adhesion is influenced by the chemical properties of the polymeric surface. These results may be interpreted taking into account a mechanism in which the acid/base (Lewis) interaction plays an important role.

Continuous monitoring of myocardial acid-base status during intermittent warm blood cardioplegia.

OBJECTIVE: Intermittent warm blood cardioplegia (IWBC) is a well-established technique for myocardial protection during cardiac operations. According to standardized protocols, IWBC administration is currently performed every 15-20 min regardless of any individual variable and in the absence of any instrumental monitoring. We devised a new system for continuous measurement of the acid-base status of coronary sinus blood for on-line evaluation of myocardial oxygenation during IWBC. METHODS: In 19 patients undergoing cardiac surgery for coronary artery bypass graft and/or valve surgery and receiving IWBC (34-37 degrees C) by antegrade induction (3 min) and retrograde or antegrade maintenance (2 min) every 15 min, continuous monitoring of myocardial oxygenation and acid/base status was performed by means of a multiparameter PO(2), PCO(2), pH, and temperature sensor (Paratrend7 (R), Philips Medical System) inserted into the coronary sinus. RESULTS: Mean cross-clamping time was 76+/-26 min; ischemic time was 13+/-0.2 min. pH decline was not linear, showing an initial fast decline, a point of flexus, and a progressive slow decline. After every ischemic period, the pH adaptation curve showed a complex pattern reaching step-by-step lower minimum levels (7.28+/-0.14 during the first ischemic period, to 7.16+/-0.19 during the third ischemic period - P=0.003). PO(2) decreased rapidly at 90% in 5.0+/-1.2 min after every reperfusion. During ischemia, PCO(2) increased steadily at 1.6+/-0.1 mmHg per minute, with progressively incomplete removal after successive reperfusion, and progressive increase of maximal level (42+/-12 mmHg during the first ischemic period, to 53+/-23 mmHg during the third ischemic period - P=0.05). CONCLUSIONS: Myocardial oxygen, carbon dioxide, and pH show marked changes after repeated IWBC. Myocardial ischemia is not completely reversed by standardized reperfusions, as reflected by steady deterioration of PCO(2) and pH after each reperfusion. Progressive increase of reperfusion durations or direct monitoring of myocardial oxygenation could be advisable in cases of prolonged cross-clamping time.

Orthotopic heart transplantation: standard versus bicaval technique.

We compared orthotopic heart transplantation (HT) by bicaval technique with the standard technique. Between January 1995 and December 1997, 117 patients underwent 118 HTs; 71 patients (15 women and 56 men) had 72 HTs by standard technique and 46 patients (9 women, 37 men) underwent HT using bicaval procedures. Preoperative parameters were similar in both groups; 5 patients who underwent the standard technique and no patients who underwent bicaval procedures required permanent pacemakers (p = NS). Isoproterenol infusion was significantly longer in the standard technique. Major perioperative arrhythmias (ventricular tachycardia and fibrillation, asystole) appeared in 8.2% and 7.0% of standard and bicaval HTs, respectively; atrial fibrillation appeared in 13.1% and 4.6%, respectively (p = NS). At 1 month, mitral and tricuspid regurgitation rates were higher in the standard group (p = NS); at 1 year only tricuspid regurgitation was still higher (p = NS). Right atrial pressure, Wood units, cardiac output, and cardiac index were examined (p = NS). At multivariate analysis, interaction between preoperative Wood units and transplant type was elicited for Wood units at 1 month and for right atrial pressure at 1, 3, and 6 months. In the high resistance subgroup, the patients who underwent bicaval procedures had higher resistances at 1 month. In the low resistance subgroup, right atrial pressure was higher in patients who underwent standard techniques at 1, 3, and 6 months follow-up. Thus, bicaval HT was found to be safe, without surgically related complications, it provoked significantly less blood loss, and required less isoproterenol use. No significant advantages were observed in conduction disturbances and major arrhythmias or regarding the need for temporary or permanent pacemakers.

The spectrum of aortic complications after heart transplantation.

BACKGROUND: The connection between the donor and the recipient aorta is a potential source of early and late complications as a result of infection, compliance mismatch, and technical and hemodynamic factors. Moreover, the abrupt change in systolic pressure after heart transplantation involves the entire thoracic aorta in the risk of aneurysm formation. The aim of this study was to analyze the types of aortic complications encountered in our heart transplantation series and to discuss etiology, diagnostic approach, and modes of treatment. METHODS: Of the 442 patients having orthotopic heart transplantation and the 11 patients having heterotopic heart transplantation at our center, 9 (2%) sustained complications involving the thoracic aorta. These 9 patients were divided into four groups according to the aortic disease: acute aortic rupture (2 patients); infective pseudoaneurysm (3 patients); true aneurysm and dissection of native aorta (2 patients); and aortic dissection after heterotopic heart transplantation (2 patients). Surgical intervention was undertaken in 8. RESULTS: Five (83%) of 6 patients who underwent surgical treatment for noninfective complications survived the operation, and 4 are long-term survivors. One patient who underwent a Bentall procedure 71/2 years after heterotopic heart transplantation died in the perioperative period of low-output syndrome secondary to underestimated chronic rejection of the graft. One patient with pseudoaneurysm survives without surgical treatment but died several years later of cardiac arrest due to chronic rejection. Both patients operated on for evolving infective pseudoaneurysm died in the perioperative period. CONCLUSIONS: Infective pseudoaneurysms of the aortic anastomosis are associated with a significant mortality. In noninfective complications, an aggressive surgical approach offers good long-term results. The possibility of retransplantation in spite of complex surgical repair should be considered in the late follow-up after heart transplantation, due to the increasing incidence of chronic rejection.