RESUMO
Pre-weaned porcine islets (PPIs) represent an unlimited source for islet transplantation but are functionally immature. We previously showed that necrostatin-1 (Nec-1) immediately after islet isolation enhanced the in vitro development of PPIs. Here, we examined the impact of Nec-1 on the in vivo function of PPIs after transplantation in diabetic mice. PPIs were isolated from pancreata of 8-15-day-old, pre-weaned pigs and cultured in media alone, or supplemented with Nec-1 (100 µM) on day 0 or on day 3 of culture (n = 5 for each group). On day 7, islet recovery, viability, oxygen consumption rate, insulin content, cellular composition, insulin secretion capacity, and transplant outcomes were evaluated. While islet viability and oxygen consumption rate remained high throughout 7-day tissue culture, Nec-1 supplementation on day 3 significantly improved islet recovery, insulin content, endocrine composition, GLUT2 expression, differentiation potential, proliferation capacity of endocrine cells, and insulin secretion. Adding Nec-1 on day 3 of tissue culture enhanced the islet recovery, proportion of delta cells, beta-cell differentiation and proliferation, and stimulation index. In vivo, this leads to shorter times to normoglycemia, better glycemic control, and higher circulating insulin. Our findings identify the novel time-dependent effects of Nec-1 supplementation on porcine islet quantity and quality prior to transplantation.
Assuntos
Diabetes Mellitus Experimental/terapia , Imidazóis/farmacologia , Indóis/farmacologia , Transplante das Ilhotas Pancreáticas/métodos , Ilhotas Pancreáticas/efeitos dos fármacos , Técnicas de Cultura de Tecidos/métodos , Animais , Diabetes Mellitus Experimental/metabolismo , Insulina/metabolismo , Ilhotas Pancreáticas/fisiologia , Camundongos Nus , Suínos , Transplante Heterólogo/métodos , Transplantes/efeitos dos fármacos , Transplantes/fisiologiaRESUMO
We studied immunolocalization of CD29, CD44, osteocalcin, and TGF-ß1 in the bone tissue of the mandible of miniature pigs with extra-bone fixation of a free gingival graft. Three months after surgery, neoosteogenesis foci with high expression of the studied markers were found in the contact area of the free gingival graft with the alveolar bone. The markers were localized in the layer of external circumferential lamellae, on the surface of concentric lamellae of the growing osteons, and in the connective tissue of the Haversian canals. TGF-ß1-immunopositive cells predominated in the connective tissue of the Haversian and Volkmann canals and in the adventitia and inner lining of the vascular wall. The established morphochemical patterns of osteogenous cells indicate significant reparative capabilities of a free gingival graft and allows considering it as an effective osteoinductive factor.
Assuntos
Enxerto de Osso Alveolar/métodos , Gengiva/transplante , Mandíbula/cirurgia , Osteogênese/genética , Regeneração/genética , Transplantes/fisiologia , Enxerto de Osso Alveolar/instrumentação , Animais , Biomarcadores/metabolismo , Pinos Ortopédicos , Expressão Gênica , Gengiva/cirurgia , Receptores de Hialuronatos/genética , Receptores de Hialuronatos/metabolismo , Integrina beta1/genética , Integrina beta1/metabolismo , Masculino , Osteocalcina/genética , Osteocalcina/metabolismo , Dispositivos de Fixação Cirúrgica , Suínos , Porco Miniatura , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismoRESUMO
Primary graft dysfunction (PGD) and ischemia-reperfusion injury (IRI) occur in up to 30% of patients undergoing lung transplantation and may impact on the clinical outcome. Several strategies for the prevention and treatment of PGD have been proposed, but with limited use in clinical practice. In this study, we investigate the potential application of sevoflurane (SEV) preconditioning to mitigate IRI after lung transplantation. The study included two groups of swines (preconditioned and not preconditioned with SEV) undergoing left lung transplantation after 24-hour of cold ischemia. Recipients' data was collected for 6 hours after reperfusion. Outcome analysis included assessment of ventilatory, hemodynamic, and hemogasanalytic parameters, evaluation of cellularity and cytokines in BAL samples, and histological analysis of tissue samples. Hemogasanalytic, hemodynamic, and respiratory parameters were significantly favorable, and the histological score showed less inflammatory and fibrotic injury in animals receiving SEV treatment. BAL cellular and cytokine profiling showed an anti-inflammatory pattern in animals receiving SEV compared to controls. In a swine model of lung transplantation after prolonged cold ischemia, SEV showed to mitigate the adverse effects of ischemia/reperfusion and to improve animal survival. Given the low cost and easy applicability, the administration of SEV in lung donors may be more extensively explored in clinical practice.
Assuntos
Precondicionamento Isquêmico/métodos , Transplante de Pulmão/métodos , Traumatismo por Reperfusão , Sevoflurano , Transplantes , Administração por Inalação , Anestésicos Inalatórios/administração & dosagem , Anestésicos Inalatórios/farmacologia , Animais , Modelos Animais de Doenças , Pulmão/efeitos dos fármacos , Pulmão/fisiologia , Transplante de Pulmão/mortalidade , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/fisiopatologia , Sevoflurano/administração & dosagem , Sevoflurano/farmacologia , Sus scrofa , Suínos , Transplantes/efeitos dos fármacos , Transplantes/fisiologiaRESUMO
OBJECTIVES: Ex vivo lung perfusion provides an innovative method to assess and repair donor lungs. The current Toronto ex vivo lung perfusion protocol can reliably and reproducibly preserve lungs for 12 hours. A longer ex vivo lung perfusion preservation time could enable the application of more advanced repair therapies and the rescue of more donor lungs for lung transplant. Our objective was to achieve stable 24-hour normothermic ex vivo lung perfusion. METHODS: We systematically examined 3 modifications of ex vivo lung perfusion perfusate administration in a large animal 24-hour ex vivo lung perfusion model. Pig lungs were assigned to 4 groups (n = 5 per group): (1) control; (2) continuous replacement of ex vivo lung perfusion perfusate; (3) modified feed, which used a modified solution to maintain perfusate osmolality by adjusting glucose and sodium levels; and (4) total parenteral nutrition, in which we added parenteral nutrition to the perfusate. RESULTS: Only 1 lung in the control group completed 24-hour ex vivo lung perfusion. However, 24-hour perfusion was achieved in 4 lungs in the continuous replacement group, 3 lungs in the modified feed group, and 4 lungs in the total parenteral nutrition group. The total parenteral nutrition group achieved significantly longer stable perfusion time compared with control (P = .03). Lung function was significantly improved and inflammatory cytokine production was reduced in the continuous replacement and total parenteral nutrition groups compared with control. CONCLUSIONS: Modifications of ex vivo lung perfusion perfusate toward achieving a stable homeostatic state can extend perfusion time for up to 24 hours. Although these modifications allow for prolonged ex vivo lung perfusion, further research will be required to develop stable lung support beyond 24 hours.
Assuntos
Homeostase/fisiologia , Pulmão/fisiologia , Preservação de Órgãos/métodos , Perfusão/métodos , Transplantes/fisiologia , Animais , Transplante de Pulmão , Masculino , Nutrição Parenteral Total , SuínosRESUMO
BACKGROUND: Cardiopulmonary bypass (CPB) induces a systemic inflammatory response (SIRS) and affects the organ vascular bed. Experimentally, the lack of pulsatility alters myogenic tone of resistance arteries and increases the parietal inflammatory response. The purpose of this study was to compare the vascular reactivity of the internal thoracic arteries (ITAs) due to the inflammatory response between patients undergoing coronary artery bypass grafting (CABG) under CPB with a roller pump or with a centrifugal pump. METHODS: Eighty elective male patients undergoing CABG were selected using one or two internal thoracic arteries under CPB with a roller pump (RP group) or centrifugal pump (CFP group). ITA samples were collected before starting CPB (Time 1) and before the last coronary anastomosis during aortic cross clamping (Time 2). The primary endpoint was the endothelium-dependent relaxation of ITAs investigated using wire-myography. The secondary endpoint was the parietal inflammatory response of arteries defined by the measurements of superoxide levels, leukocytes and lymphocytes rate and gene expression of inflammatory proteins using. Terminal complement complex activation (SC5b-9) and neutrophil activation (elastase) analysis were performed on arterial blood at the same times. RESULTS: Exposure time of ITAs to the pump flow was respectively 43.3 minutes in the RP group and 45.7 minutes in the CFP group. Acetylcholine-dependent relaxation was conserved in the two groups whatever the time. Gene expression of C3 and C4a in the artery wall decreased from Time 1 to Time 2. No oxidative stress was observed in the graft. There was no difference between the groups concerning the leukocytes and lymphocytes rate. SC5b-9 and elastase increased between Time 1 and Time 2. CONCLUSION: Endothelium-dependent relaxation of the internal thoracic arteries was preserved during CPB whatever the type of pump used. The inflammatory response observed in the blood was not found in the graft wall within this time frame. TRIAL REGISTRATION: Name of trial study protocol: IPITA Registration number (ClinicalTrials.gov): NCT04168853.
Assuntos
Ponte Cardiopulmonar/instrumentação , Ponte de Artéria Coronária/métodos , Coração Auxiliar/efeitos adversos , Artéria Torácica Interna/cirurgia , Complicações Pós-Operatórias/etiologia , Idoso , Idoso de 80 Anos ou mais , Ponte Cardiopulmonar/efeitos adversos , Ponte Cardiopulmonar/métodos , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/instrumentação , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiologia , Feminino , Humanos , Elastase de Leucócito/metabolismo , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Complicações Pós-Operatórias/epidemiologia , Transplantes/fisiologia , Transplantes/cirurgia , Vasoconstrição , VasodilataçãoRESUMO
INTRODUCTION: Early repair in patients affected by myelomeningocele (MMC) is of paramount importance in order to prevent infection, minimize neural tissue damage, and reduce mortality. Treatment must include duraplasty and possibly an adequate soft tissue coverage. Delayed surgery in MMC patients can be more tedious due to the less clear borders between the placode and the skin. Moreover, the risks of wound infection and breakdown increase significantly. CASE PRESENTATION: We present the unusual case of a large MMC in a 3-year-old patient treated by combining the recently described cryopreserved amniotic membrane (AM) as homograft for dural reconstruction and a bilateral Keystone flap for soft tissue reconstruction. DISCUSSION: Thanks to its anti-inflammatory and elastic proprieties, the AM can play an important role in preventing adhesion between the reconstructed layers, thus reducing the risk of spinal cord tethering. The Keystone flap, at the same time, allows the wound tension to be distributed widely over the flap margins and not only along the midline, which overlies the duraplasty, enhancing the scar quality and lowering the risk of cerebrospinal fluid recurrence and wound dehiscence, with no donor site morbidity.
Assuntos
Aloenxertos/transplante , Âmnio/transplante , Criopreservação , Meningomielocele/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos/transplante , Âmnio/fisiologia , Pré-Escolar , Feminino , Seguimentos , Humanos , Região Lombossacral/diagnóstico por imagem , Região Lombossacral/cirurgia , Meningomielocele/diagnóstico por imagem , Retalhos Cirúrgicos/fisiologia , Transplantes/fisiologia , Transplantes/transplanteRESUMO
Biolasol is a newly developed preserving solution for cold organ storage prior to transplantation. To date, only animal model experiments results are available. The aim of this single-center analysis was to summarize the clinical experience concerning the early post-transplant course of kidney grafts preserved with Biolasol in comparison with other preservation solutions. Before transplantation, 173 kidney grafts were preserved using Biolasol and 240 organs with other solutions (University of Wisconsin-UW, Institute Georges Lopez-IGL-1, or StoreProtect Plus solutions). Early graft function was defined based on serum creatinine concentration at day 3 (<3 mg/dL-immediate graft function, IGF or >3 mg/dL-slow graft function, SGF) or the need of dialysis therapy during first post-operative week (delayed graft function, DGF). The analysis included intrarenal resistive indices measured by Doppler sonography early after transplantation and before discharge from the hospital. IGF was more frequent in patients with organs preserved with IGL-1 (33.5%) and StoreProtect Plus (38.8%) than Biolasol (18.5%), whereas there was no difference in the occurrence of DGF. Both initial and discharge median resistance index values were significantly higher in the Biolasol subgroup (0.77 and 0.75) than in all three other subgroups (P values for all comparisons <.001), also after 1:1 propensity score matching for baseline characteristics. Multiple logistic regression analysis based on the propensity score-matched cohort revealed that the use of Biolasol solution [OR 0.59 (0.35-0.98); P < .05] independently decreased the occurrence of IGF. In our single-center clinical experience, kidney preservation using Biolasol solution was associated with significantly higher intrarenal resistant index in comparison with other preservation fluids, as well as worse early graft function than in the IGL-1 and the StoreProtect Plus subgroups. Long-term follow-up is needed in order to assess the kidney graft and patient survival.
Assuntos
Transplante de Rim , Rim/fisiologia , Preservação de Órgãos/métodos , Transplantes/fisiologia , Feminino , Humanos , Rim/efeitos dos fármacos , Testes de Função Renal , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Soluções para Preservação de Órgãos/farmacologia , Transplantes/efeitos dos fármacosRESUMO
BACKGROUND: The 2 main objectives regarding living kidney transplant are to provide optimal graft function and to ensure the safety of donation. Our study hypothesized that the glomerular filtration rate of a single kidney (skGFR), when transplanted, might predict graft function and that the skGFR of the remaining kidney could predict donor functional gain. METHODS: A prospective monocentric study was conducted at Grenoble-Alpes University Hospital. Twenty couples of donors and recipients were included. Dimercaptosuccinic acid renal scintigraphy and 51Cr-ethylene-diamine tetra-acetic acid clearance were evaluated predonation to calculate skGFR. All patients had renal function according to 51Cr-ethylene-diamine tetra-acetic acid clearance at 1 year post transplant to assess graft function and donor functional gain. All donors had normal renal function predonation. RESULTS: At 1 year post transplant, median glomerular filtration rate of the graft was 50 mL/min/1.73 m2 (range, 46-56 mL/min/1.73 m2) and donor median glomerular filtration rate was 59 mL/min/1.73 m2 (range, 55-74 mL/min/1.73 m2). Median functional gain was 20 mL/min/1.73 m2 (range, 12-22 mL/min/1.73 m2). No statistical correlation was found between skGFR of the transplanted kidney and graft function at 1 year (R2 = 0.096, P = .7). For the donor, functional gain was not associated with predonation skGFR of the remaining kidney (R2 = 0.17, P = .5). A statistical difference was found between donor functional gain (18 [SD, 10] mL/min) and recipient gain (delta between skGFR before and after transplant, 7 [SD, 16] mL/min; P = .02). CONCLUSION: Predonation skGFR of the transplanted kidney had no influence on renal allograft function at 1 year post transplant. Similarly, there was no association between measured skGFR of the remaining kidney and donor functional gain at 1 year.
Assuntos
Taxa de Filtração Glomerular/fisiologia , Transplante de Rim/métodos , Rim/fisiologia , Doadores Vivos , Transplantes/fisiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Transplante Homólogo , Resultado do TratamentoRESUMO
Control of patterning and the specification of body axes are fundamental aspects of animal development involving complex interactions between chemical, physical, and genetic signals. The freshwater polyp Hydra has long been recognized as a useful model system to address these questions due to its simple anatomy, optical transparency, and strong regenerative abilities, which enabled clever grafting experiments to alter and probe patterning. Reliable methods exist for the transplantation of small tissue pieces into the body column or the combination of sections cut perpendicular to the body axis, which can be used to examine oral-aboral gradients and axis induction potential of tissue fragments. However, existing methods do not allow researchers to probe questions of axis alignment and lateral information exchange. We therefore developed a technique to produce chimeric animals split longitudinally along the body axis of the animal by anesthetizing the animals with the terpene linalool and threading the donor pieces onto pairs of fine glass needles. Our novel approach can be applied to study questions in Hydra research that have thus far been inaccessible, including patterning processes acting perpendicular to the oral-aboral axis and the extent of lateral cell migration.
Assuntos
Padronização Corporal/genética , Regeneração/genética , Transplante de Tecidos/métodos , Monoterpenos Acíclicos/farmacologia , Animais , Quimera/genética , Hydra/genética , Hydra/metabolismo , Transplantes/fisiologiaRESUMO
BACKGROUND: The Living Kidney Donor Profile Index (LKDPI) was recently created. This model predicts recipient risk of graft loss after living donor transplant. Herein, we applied the LDKPI to our population to analyze its performance. METHODS: A retrospective analysis of all living donor kidney transplants from 2003 to 2018 from 2 transplant centers in Veracruz, Mexico, was used. LKDPI was calculated in a webpage (www.transplantmodels.com). Donor and recipient demographics and transplant data included in the model were registered. Pearson correlation between the LKDPI percentage and death-censored graft survival was performed. Kaplan-Meier survival (log-rank) and Cox regression analysis were compared between the LKPDI quartiles. P < .05 was considered statistically significant. RESULTS: In total, 821 transplants were included (mean age 31.7 ± 10.5 years, 62.5% male, n = 513). Mean follow-up was 64.7 ± 46.2 months. Mean estimated survival (Kaplan-Meier) was 128.9 ± 3 months (95% confidence interval [CI], 123-134). Ten-year death-censored graft survival was 61.4%. Median LKPDI was -2%, and mean LKDPI was -2.6% ± 14.6% (range, -50% to 42%). Pearson coefficient correlation between the LKDPI and death-censored graft survival was 0.024 (P = .4). Area under the curve (receiver operating characteristic [ROC]) for the LKDPI and death-censored graft loss was 0.54 (95% CI, 0.505-0.591) (P = .04). Recipients with the lowest LKDPI had lower risk of death-censored graft loss than other quartiles (P = .014 log-rank). Cox regression analysis was significant for the lower LKDPI quartile (<20%) (Exp B = 0.35; 95% CI, 0.14-0.9; P = .03). CONCLUSION: The LKDPI applies with moderate discrimination predictive power in our population. The best LKDPI patient has better death-censored graft survival. Further studies might continue to validate the LKDPI in other cohorts.
Assuntos
Sobrevivência de Enxerto , Transplante de Rim , Doadores Vivos/provisão & distribuição , Transplantes/fisiologia , Adulto , Feminino , Humanos , Transplante de Rim/mortalidade , Masculino , México , Pessoa de Meia-Idade , Curva ROC , Análise de Regressão , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Ex vivo lung perfusion (EVLP) permits extended evaluation of donor lungs for transplant. However, the optimal EVLP duration of Lund protocol is unclear. Using human lungs rejected for clinical transplant, we sought to compare the results of 1 versus 2 h of EVLP using the Lund protocol. METHODS: Twenty-five pairs of human lungs rejected for clinical transplant were perfused with the Lund EVLP protocol. Blood gas analysis, lung compliance, bronchoscopy assessment, and perfusate cytokine analysis were performed at both 1 and 2 h. Recruitment was performed at both time points. Donor lung transplant suitability was determined at both time points. RESULTS: All cases were divided into four groups based on transplant suitability assessment at 1 h and 2 h of EVLP. In group A (n = 10), lungs were judged suitable for transplant at both 1 and 2 h of EVLP. In group B (n = 6), lungs were suitable at 1 h but nonsuitable at 2 h. In group C (n = 2), lungs were nonsuitable at 1 h but suitable at 2 h. Finally, in group D (n = 7), lungs were nonsuitable for transplant at both time points. In both groups B and C (n = 8), the transplant suitability assessment changed between 1 and 2 h of EVLP. CONCLUSIONS: In human lungs rejected for transplant, transplant suitability differed at 1 versus 2 h of EVLP in 32% of lungs studied. Evaluation of lungs with Lund protocol EVLP beyond 1 h may improve donor organ assessment.
Assuntos
Seleção do Doador/métodos , Transplante de Pulmão/normas , Pulmão/fisiologia , Perfusão , Transplantes/fisiologia , Adulto , Broncoscopia , Seleção do Doador/normas , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Troca Gasosa Pulmonar/fisiologia , Fatores de Tempo , Transplantes/diagnóstico por imagemRESUMO
PURPOSE: The purpose of the study was to determine the change in the graft bending angles at the femoral and tibial tunnel aperture in single-bundle posterior cruciate ligament (PCL) reconstruction. It was hypothesized that different knee flexion and different tunnel directions may affect changes of the femoral and tibial graft bending angle. METHODS: The right knees of 12 male subjects were scanned with a high-resolution computed tomography scanner at 4 different knee flexion angles (0°, 45°, 90° and 135°). To begin with, the 3D knee models were created and manipulated with the use of several modeling programs. Single-bundle PCL reconstruction was then virtually conducted in a 90° flexion model: The femoral and tibial graft bending angle, according to the various knee flexion angles, was calculated using a special software program. RESULTS: The femoral graft bending angle significantly decreased as the knee flexion increased between 0° and 135° (all p < 0.001). The femoral graft bending angle of the AL graft showed the most obtuse angles among the three types of the graft beyond 45° of knee flexion. For the tibial graft bending angle, the anteromedial tunnel group showed significantly more acute tibial graft bending angle than the anterolateral tunnel group in all three types of the graft at all flexion angles (all p < 0.001). CONCLUSION: Changes in the femoral graft bending angle were generally affected by different knee flexion angles. The effect of tibial tunnel direction on the tibial graft bending angle was found to be significant. The clinical relevance is that a mostly obtuse femoral graft bending angle was shown by the AL graft among three types of the graft.
Assuntos
Articulação do Joelho/fisiologia , Reconstrução do Ligamento Cruzado Posterior/métodos , Ligamento Cruzado Posterior/fisiologia , Ligamento Cruzado Posterior/cirurgia , Transplantes/fisiologia , Adulto , Fêmur/cirurgia , Humanos , Imageamento Tridimensional , Articulação do Joelho/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Ligamento Cruzado Posterior/diagnóstico por imagem , Ligamento Cruzado Posterior/lesões , Amplitude de Movimento Articular , Tíbia/cirurgia , Tomografia Computadorizada por Raios X , Transplantes/diagnóstico por imagemRESUMO
Osteochondral grafts are used clinically to repair cartilage and bone defects and to restore the congruent articulating surfaces of the knee joint following cartilage damage or injury. The clinical success of such osteochondral grafts is heavily reliant on the biomechanical and tribological properties of the surgical repair; however, a limited number of studies have investigated these factors. The aim of this study was to evaluate the influence of graft harvesting and implantation technique as well as bone properties on the primary stability of press-fit implanted osteochondral grafts using a series of uniaxial experimental push-in and push-out tests. Animal (porcine and bovine) knees were used to deliver models of different bone properties (elastic modulus and yield stress). The study showed the graft harvesting method using either a chisel or drill-aided trephine to have no influence on primary graft stability; however, the preparation technique for the graft recipient site was shown to influence the force required to push the graft into the host tissue. For example, when the length of the graft was equal to the recipient site (bottomed), the graft was more stable and dilation of the recipient site was shown to reduce short-term graft stability especially in immature or less dense bone tissue. The push-out tests which compared tissue of different skeletal maturities demonstrated that the maturity of both the graft and host bone tissue to influence the stability of the graft. A higher force was required to push out more skeletally mature grafts from mature bone tissue. The study demonstrates the importance of surgical technique and bone quality/properties on the primary stability and ultimately, the success of osteochondral grafts in the knee.
Assuntos
Fenômenos Biomecânicos/fisiologia , Cartilagem Articular , Fêmur , Articulação do Joelho , Transplantes , Animais , Cartilagem Articular/fisiologia , Cartilagem Articular/transplante , Bovinos , Módulo de Elasticidade , Fêmur/fisiologia , Fêmur/cirurgia , Instabilidade Articular , Articulação do Joelho/fisiologia , Articulação do Joelho/cirurgia , Modelos Biológicos , Suínos , Transplantes/fisiologia , Transplantes/cirurgiaRESUMO
PURPOSE: Tunnel enlargement and graft rupture are common complications associated with ACL reconstruction (ACLR). This study aims to explore how variations in graft stiffness and shape affect the strain energy density (SED) around bone tunnel entrances and stress on the graft and subsequently influencing the level of tunnel enlargement and graft wear. METHODS: Finite element ACLR models were developed using different graft stiffnesses (323 N/mm, 545 N/mm and 776 N/mm) and shapes (circular and elliptical). The models were subjected to a combined loading of 103 N anterior tibial load, 7.5 Nm internal tibial moment, and 6.9 Nm valgus tibial moment at joint flexion of 30°. SED at tunnel entrances and stresses on the graft was recorded and compared among the different models. RESULTS: Increasing the graft stiffness resulted in greater stress on the graft (17.2, 24.4 and 31.7 MPa for graft stiffnesses of 323 N/mm, 545 N/mm and 776 N/mm), but had little effect on the SED reduction around the tunnel entrances. Changing the cross section of the graft from circular to elliptical caused an additional reduction in SED (56.8 vs 2.8 kJ/m3) at the posterior zone of the femoral tunnel entrance and increased the stress on the graft (31.7 MPa vs 38.9 MPa). CONCLUSIONS: This study recommends using ACL grafts with lower stiffness and a circular cross section to reduce tunnel enlargement and graft wear following ACLR.
Assuntos
Reconstrução do Ligamento Cruzado Anterior/efeitos adversos , Modelos Biológicos , Transplantes/fisiologia , Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/cirurgia , Fenômenos Biomecânicos , Cadáver , Elasticidade , Fêmur/cirurgia , Análise de Elementos Finitos , Humanos , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Ruptura , Tíbia/cirurgiaRESUMO
OBJECTIVE: Ex vivo lung perfusion (EVLP) is reportedly a useful strategy that permits marginal donor lungs to be evaluated and reconditioned for successful lung transplantation (LTx). This systematic review and meta-analysis was performed to evaluate the outcomes of EVLP conducted for marginal donor lungs. METHODS: We searched PubMed, the Cochrane Library, and Embase to select studies describing the results of LTx following EVLP for marginal donor lungs compared with standard LTx without EVLP. We performed a meta-analysis to examine donor baseline characteristics, recipient baseline characteristics, and postoperative outcomes. RESULTS: Of 1380 studies, 8 studies involving 1191 patients met the inclusion criteria. Compared with the non-EVLP group (ie, standard LTx without EVLP), the EVLP group (ie, EVLP of marginal donors following LTx) had similar donor age and sex and recipient baseline age, sex, body mass index, bridge by ventilator/extracorporeal life support/extracorporeal membrane oxygenation, and rate of double LTx but more abnormal donor lung radiographs (P = .0002), a higher smoking history rate (P = .03), and worse donor arterial oxygen tension/inspired oxygen fraction (P < .00001). However, there were no significant differences in outcomes between the EVLP and non-EVLP groups with respect to the length of postoperative intubation, postoperative extracorporeal life support/extracorporeal membrane oxygenation use, length of intensive care unit stay, length of hospital stay, 72-hour primary graft dysfunction of grade 3, 30-day survival, or 1-year survival (all P values > .05). CONCLUSIONS: Posttransplant outcomes were similar between EVLP-treated LTx and standard LTx without EVLP, although the quality of donor lungs was worse with EVLP-treated LTx.
Assuntos
Transplante de Pulmão , Pulmão , Transplantes , Adulto , Idoso , Feminino , Humanos , Pulmão/fisiologia , Pulmão/fisiopatologia , Transplante de Pulmão/efeitos adversos , Transplante de Pulmão/métodos , Transplante de Pulmão/mortalidade , Masculino , Pessoa de Meia-Idade , Preservação de Órgãos , Perfusão , Doadores de Tecidos , Obtenção de Tecidos e Órgãos , Transplantes/fisiologia , Transplantes/fisiopatologia , Transplantes/transplanteAssuntos
Hibernação/fisiologia , Preservação de Órgãos/métodos , Traumatismo por Reperfusão/terapia , Transplantes/fisiologia , Adenilato Quinase/metabolismo , Animais , Criobiologia , Heme Oxigenase-1/metabolismo , Humanos , Sulfeto de Hidrogênio/metabolismo , Modelos Animais , Receptores Opioides/metabolismo , Transplantes/transplanteRESUMO
Due the shortage of organ donors and the increase in the waiting list of kidney transplant recipients (KTR), alternative strategies have been considered with the aim of increasing the number of organs available. The use of kidneys from donors with acute renal failure and elevated serum creatinine has been considered as a way to increase the number of donors. The objective of this work is to report the 3-year follow-up of three KTR patients of a deceased donor with serum creatinine greater than or equal to 5 mg/dL.
Ante la escasez de donadores de órganos y el incremento en la lista de espera de receptores de trasplante renal (RTR) se han considerado medidas alternativas con el objetivo de aumentar el número de órganos disponibles. El uso de riñones de donadores con insuficiencia renal aguda y creatinina sérica terminal elevada se ha considerado un camino para incrementar el número de donadores. El objetivo de este trabajo es notificar el seguimiento a tres años de tres pacientes RTR de donador fallecido con creatinina sérica ≥ 5 mg/dl.
Assuntos
Injúria Renal Aguda/sangue , Creatinina/sangue , Transplante de Rim , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/normas , Adulto , Cadáver , Carcinoma de Células Renais/cirurgia , Nefropatias Diabéticas/complicações , Feminino , Seguimentos , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Humanos , Rim/fisiologia , Falência Renal Crônica/etiologia , Falência Renal Crônica/cirurgia , Neoplasias Renais/cirurgia , Masculino , Nefrectomia , Reoperação , Transplantes/fisiologia , Resultado do Tratamento , Refluxo Vesicoureteral/complicações , Adulto JovemRESUMO
Respiratory diseases are among the leading causes of death and disability worldwide. However, the pathogenesis of both acute and chronic lung diseases remains incompletely understood. As a result, therapeutic options for important clinical problems, including acute respiratory distress syndrome and chronic obstructive pulmonary disease, are limited. Research efforts have been held back in part by the difficulty of modeling lung injury in animals. Donor human lungs that have been rejected for transplantation offer a valuable alternative for understanding these diseases. In 2007, our group developed a simple preparation of an ex vivo-perfused single human lung. In this Review, we discuss the availability of donor human lungs for research, describe the ex vivo-perfused lung preparation, and highlight how this preparation can be used to study the mechanisms of lung injury, to isolate primary cells, and to test novel therapeutics.
Assuntos
Pulmão , Modelos Biológicos , Pesquisa Translacional Biomédica/métodos , Transplantes , Humanos , Pulmão/citologia , Pulmão/fisiologia , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica , Transplantes/citologia , Transplantes/fisiologia , Transplantes/fisiopatologiaRESUMO
IMPACT STATEMENT: Over the past several decades, ex vivo perfusion has emerged as a promising technology for the assessment, preservation, and recovery of donor organs. Many exciting pre-clinical findings have now been translated to clinical use, and successful transplantation following ex vivo perfusion has been achieved for heart, lung, and liver. While machine perfusion provides distinct advantages over traditional cold preservation, many challenges remain, including that of long-term (multi-day) ex vivo support. Here, we provide an overview of the current status of ex vivo machine perfusion in the pre-clinical and clinical setting and share our perspective on the future direction of the field.
Assuntos
Bioengenharia , Preservação de Órgãos/métodos , Perfusão/métodos , Cadáver , Isquemia Fria/efeitos adversos , Isquemia Fria/instrumentação , Isquemia Fria/métodos , Previsões , Coração/fisiologia , Transplante de Coração , Humanos , Fígado/fisiologia , Transplante de Fígado , Pulmão/fisiologia , Transplante de Pulmão , Preservação de Órgãos/instrumentação , Perfusão/instrumentação , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Coleta de Tecidos e Órgãos/métodos , Transplantes/fisiologia , Isquemia Quente/efeitos adversosRESUMO
OBJECTIVES: The different mechanical and vasodilatory properties of arteries and veins may influence their flow profiles when used for coronary artery bypass grafting (CABG). This may be of significance when assessing the cut-off values for adequate flow. However, conduit-related flow differences are less examined. METHODS: In a study of 268 patients, transit time flowmetry parameters of 336 arterial and 170 venous conduits all grafted to the left coronary territory were compared. With transit time flowmetry, the mean graft flow (MGF), pulsatility index, percentage of diastolic filling and percentage of backwards flow were measured. Conduit-related differences were further compared according to on- or off-pump CABG (ONCABG versus OPCABG) surgery. RESULTS: Overall MGF and pulsatility index were comparable between arterial and venous grafts, but in arterial grafts, MGF was higher during ONCABG than during OPCABG (49.1 ± 35.3 ml/min vs 38.8 ± 26.6 ml/min; P = 0.003). Percentage of diastolic filling was higher in arterial grafts than in venous grafts (overall 71.0 ± 7.9% vs 63.7 ± 11.1%; ONCABG 69.9 ± 7.1% vs 63.9 ± 10.4%; OPCABG 71.9 ± 8.3% vs 63.4 ± 12.2%; all P < 0.001). Furthermore, percentage of backwards flow was higher in arterial grafts than in venous grafts in the overall (2.3 ± 3.2% vs 1.7 ± 3.2%, P = 0.002) and in the ONCABG (2.3 ± 3.2% vs 1.3 ± 2.5%, P < 0.001) cohorts. In venous grafts, percentage of backwards flow was lower during ONCABG versus OPCABG (1.3 ± 2.5% vs 2.6 ± 3.9%, P = 0.016). CONCLUSIONS: No statistically significant difference was observed for MGF and pulsatility index between arterial and venous conduits. However, arterial grafts have significantly higher diastolic filling and backwards flow than venous grafts. Furthermore, arterial grafts have a significantly higher MGF in ONCABG versus OPCABG.