RESUMO
Background: Vascular endothelial growth factor A (VEGF) is an essential growth factor during glomerular development and postnatal homeostasis. VEGF is secreted in high amounts by podocytes into the primary urine, back-filtered across the glomerular capillary wall to act on endothelial cells. So far it has been assumed that VEGF back-filtration is driven at a constant rate exclusively by diffusion. Methods: In the present work, glomerular VEGF back-filtration was investigated in vivo using a novel extended model based on endothelial fenestrations as surrogate marker for local VEGF concentrations. Single nephron glomerular filtration rate (SNGFR) and/or local filtration flux were manipulated by partial renal mass ablation, tubular ablation, and in transgenic mouse models of systemic or podocytic VEGF overexpression or reduction. Results: Our study shows positive correlations between VEGF back-filtration and SNGFR as well as effective filtration rate under physiological conditions along individual glomerular capillaries in rodents and humans. Conclusion: Our results suggest that an additional force drives VEGF back-filtration, potentially regulated by SNGFR.
Assuntos
Capilares/fisiopatologia , Taxa de Filtração Glomerular/fisiologia , Glomérulos Renais/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Modelos Animais de Doenças , Glomérulos Renais/fisiopatologia , Camundongos , Camundongos Knockout , NefrectomiaAssuntos
Hipotermia Induzida/métodos , Transplante de Rim/métodos , Rim/irrigação sanguínea , Preservação de Órgãos/métodos , Traumatismo por Reperfusão/prevenção & controle , Obtenção de Tecidos e Órgãos/métodos , Condicionamento Pré-Transplante/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Preservação de Órgãos/instrumentação , Oxigênio , PerfusãoRESUMO
An air-source heat pump simulation model, accounting for evaporator and condenser pressure drop, has been developed. The model is capable of computing the heat pump's coefficient of performance (COP) under different ambient temperatures and relative humidities above frosting conditions. This research extends an existing iterative simulation method that relies on the equalization of logarithmic mean temperature differences (LMTDs) calculated through two different approaches by adding a pressure drop simulation. Frictional and acceleration pressure drop is considered, computed iteratively. Simulation results for three different refrigerants, R410A, R32 and R290, are compared. The model's accuracy is validated by comparing simulated COP values with measured COP values from the reference heat pump datasheet. The model closely replicates the measured COP values above frosting conditions, with only a slight underestimation of approximately 1.5%. Results show a substantial impact of ambient temperature on the COP. For instance, an ambient temperature of 20 â¦C, compared to 7 â¦C, results in a COP increase of up to 35%, while an ambient temperature of -10 â¦C leads to a 26% reduction in COP. Relative humidity enhances the COP if air moisture condensation becomes possible. Higher condenser capacities negatively affect the COP. The study highlights the differences in pressure drop characteristics between the condenser and the evaporator for the modeled heat pump, with maximum pressure drops of 220 kPa and 50 kPa for the condenser and evaporator, respectively. Additionally, the choice of refrigerant significantly influences pressure drop, with R32 displaying the lowest pressure drop, R410A showing the highest condenser pressure drop, and R290 causing the highest evaporator pressure drop.
RESUMO
BACKGROUND: Kidney transplantation is the only curative treatment option for end-stage renal disease. The unavailability of adequate organs for transplantation has resulted in a substantial organ shortage. As such, kidney donor allografts that would have previously been deemed unsuitable for transplantation have become an essential organ pool of extended criteria donor allografts that are now routinely being transplanted on a global scale. However, these extended criteria donor allografts are associated with significant graft-related complications. As a result, hypothermic oxygenated machine perfusion (HOPE) has emerged as a powerful, novel technique in organ preservation, and it has recently been tested in preclinical trials in kidney transplantation. In addition, HOPE has already provided promising results in a few clinical series of liver transplantations where the liver was donated after cardiac death. OBJECTIVE: The present trial is an investigator-initiated prospective pilot study on the effects of HOPE on extended criteria donor allografts donated after brain death and used in kidney transplantation. METHODS: A total of 15 kidney allografts with defined inclusion/exclusion criteria will be submitted to two hours of HOPE via the renal artery before implantation, and are going to be compared to a case-matched group of 30 patients (1:2 matching) who had kidneys transplanted after conventional cold storage. Primary (posttransplant dialysis within 7 days) and secondary (postoperative complications, early graft function, duration of hospital and intensive care unit stay, and six-month graft survival) endpoints will be analyzed within a six-month follow-up period. The extent of ischemia-reperfusion injury will be assessed using kidney tissue, perfusate, and serum samples taken during the perioperative phase of kidney transplantation. RESULTS: The results of this trial are expected in the first quarter of 2020 and will be presented at national and international scientific meetings and published in international peer-reviewed medical journals. The trial was funded in the third quarter of 2017 and patient enrollment is currently ongoing. CONCLUSIONS: This prospective study is designed to explore the effects of HOPE on extended criteria donor kidney allografts donated after brain death. The present report represents the preresults phase. TRIAL REGISTRATION: Clinicaltrials.gov NCT03378817; https://clinicaltrials.gov/ct2/show/NCT03378817.