Abstract Background Deceased after cardiac death donors (DCDs) represent a valuable source of organs; however, preventing poor outcome is difficult, even with the use of machine perfusion (MP). It is ...of paramount importance to improve this method. We proposed to evaluate the benefits of active oxygenation during kidney graft hypothermic MP using a novel perfusion machine: Kidney Assist (KA). Methods We used a pig model of DCD transplantation in Large White pigs. Cold preservation was performed by conventional non-oxygenated MP (KAnoO2 ) or oxygenated MP (KA). Results In the first 2 wk post-transplant, KA grafts displayed a lower serum creatinine peak and a faster return to normal levels compared with KAnoO2 animals, translating into a smaller area under the curve. Urinary neutrophil gelatinase-associated lipocalin levels and serum aspartate amino transferase levels were lower in KA animals compared with the non-oxygenated group. These correlated with better chronic function. Longer follow-up of the animals (3 mo) permitted evaluation of chronic outcome lesions. Interstitial fibrosis was reduced in the KA group, and these kidneys also displayed significantly lower levels of vimentin staining. Further histologic investigation also showed a trend toward decreased chronic inflammation in kidneys preserved with oxygen. Conclusions This new MP system is efficient in preserving DCD kidneys, greatly enhancing the capacity of the graft to withstand preservation stress and improving outcome. Oxygen delivery during preservation is thus valuable for highly damaged organs and offers an important therapeutic tool for transplant teams faced with decreased quality of donor organs.
The vascular network is a major target of ischemia-reperfusion, but has been poorly investigated in renal transplantation. The aim of this study was to characterize the remodeling of the renal ...vascular network that follows ischemia-reperfusion along with the most highly affected cortex section in a preclinical renal transplantation model. There were two experimental groups. The first was a grafted kidney group consisting of large white pigs for which the left kidney was harvested, cold flushed, preserved for 24 h in the University of Wisconsin's preservation solution, and then auto-transplanted (n = 5); the right kidney was removed to mimic the situation of human kidney transplantation. The second group (uni-nephrectomized kidney group) consisted of animals that underwent only right nephrectomy, but not left renal transplantation (n = 5). Three months after autotransplantation, the kidneys were studied by X-ray microcomputed tomography. Vessel morphology and density and tortuosity of the network were analyzed using a 3D image analysis method. Cortical blood flow was determined by laser doppler analysis and renal function and tissue injury assessed by plasma creatinine levels and histological analysis. Renal ischemia-reperfusion led to decreased vascular segment volume associated with fewer vessels of less than 30 μm, particularly in the inner cortex:0.79 ± 0.54% in grafted kidneys vs. 7.06 ± 1.44% in uni-nephrectomized kidneys, p < 0.05. Vessels showed higher connectivity throughout the cortex (the arborescence factor of the whole cortex was less in grafted than uni-nephrectomized kidneys 0.90 ± 0.04 vs. 1.07 ± 0.05, p < 0.05, with an increase in the number of bifurcations). Furthermore, cortical blood flow decreased early in kidney grafts and remained low three months after auto-transplantation. The decrease in microvasculature correlated with a deterioration of renal function, proteinuria, and tubular dysfunction, and was associated with the development of fibrous tissue. This work provides new evidence concerning the impact of ischemia-reperfusion injuries on the spectrum of renal vascular diseases and could potentially guide future therapy to preserve microvessels in transplantation ischemia-reperfusion injury.
Renal transplantation is increasingly associated with the presence of comorbidity factors such as dyslipidemia which could influence the graft outcome. We hypothesized that hypercholesterolemia could ...affect vascular repair processes and promote post-transplant renal vascular remodeling through the over-expression of the anti-angiogenic thrombospondin-1 interacting with vascular endothelial growth factor-A levels.
We tested this hypothesis in vitro, in vivo and in a human cohort using (1) endothelial cells; (2) kidney auto-transplanted pig subjected (n = 5) or not (n = 6) to a diet enriched in cholesterol and (3) a renal transplanted patient cohort (16 patients).
Cells exposed to oxidized LDL showed reduced proliferation and an increased expression of thrombospondin-1. In pigs, 3 months after transplantation of kidney grafts, we observed a deregulation of the hypoxia inducible factor 1a-vascular endothelial growth factor-A axis induced in cholesterol-enriched diet animals concomitant with an overexpression of thrombospondin-1 and a decrease in cortical microvessel density promoting vascular remodeling. In patients, hypercholesterolemia was associated with decreased vascular endothelial growth factor-A plasma levels during early follow up after renal transplantation and increased chronic graft dysfunction.
These results support a potential mechanism through which a high fat-diet impedes vascular repair in kidney graft and suggest the value of controlling cholesterolemia in recipient even at the early stage of renal transplantation.
We present a case of dissecting aneurysm of ascending aorta in a 15-year-old patient secondary to Takayasu arteritis with concomitant tuberculosis, with an emphasis on multimodality imaging findings ...and to illustrate preoperative and postoperative medical management. Antituberculosis therapy, high-dose corticosteroids, antiplatelet therapy, and β-blockers were administrated during the initial active phase. The patient presented with acute chest pain 3 months after medical therapy initiation. We performed an ascending aorta and aortic arch replacement with branched Dacron grafts. Only a handful of similar, but not identical, cases of Takayasu arteritis with concomitant tuberculosis leading to aortic dissection have been described previously.
The current organ shortage in hepatic transplantation leads to increased use of marginal livers. New organ sources are needed, and deceased after circulatory death (DCD) donors present an interesting ...possibility. However, many unknown remains on these donors and their pathophysiology regarding ischemia reperfusion injury (IRI). Our hypothesis was that DCD combined with abdominal normothermic regional recirculation (ANOR) is not inferior to deceased after brain death (DBD) donors. We performed a mechanistic comparison between livers from DBD and DCD donors in a highly reproducible pig model, closely mimicking donor conditions encountered in the clinic. DCD donors were conditioned by ANOR. We determined that from the start of storage, pro-lesion pathways such as oxidative stress and cell death were induced in both donor types, but to a higher extent in DBD organs. Furthermore, pro-survival pathways, such as resistance to hypoxia and regeneration showed activation levels closer to healthy livers in DCD-ANOR rather than in DBD organs. These data highlight critical differences between DBD and DCD-ANOR livers, with an apparent superiority of DCD in terms of quality. This confirms our hypothesis and further confirms previously demonstrated benefits of ANOR. This encourages the expended use of DCD organs, particularly with ANOR preconditioning.
The shortage of organs for transplantation has led health professionals to look for alternative sources of donors. One of the avenues concerns donors who have died after circulatory arrest. This is a ...special situation because the organs from these donors are exposed to warm ischaemia-reperfusion lesions that are unavoidable during the journey of the organs from the donor to the moment of transplantation in the recipient. We will address and discuss the key issues from the perspective of team organization, legislation and its evolution, and the ethical framework. In a second part, the avenues to improve the quality of organs will be presented following the itinerary of the organs between the donor and the recipient. The important moments from the point of view of therapeutic strategy will be put into perspective. New connections between key players involved in pathophysiological mechanisms and implications for innate immunity and injury processes are among the avenues to explore. Technological developments to improve the quality of organs from these recipients will be analyzed, such as perfusion techniques with new modalities of temperatures and oxygenation. New molecules are being investigated for their potential role in protecting these organs and an analysis of potential prospects will be proposed. Finally, the important perspectives that seem to be favored will be discussed in order to reposition the use of deceased donors after circulatory arrest. The use of these organs has become a routine procedure and improving their quality and providing the means for their evaluation is absolutely inevitable.
When neither surgical valve replacement nor transcatheter aortic valve implantation is possible, performing an apico-aortic conduit remains a therapeutic option. This procedure has become rare and ...the rigid angled apical connectors usually used to facilitate ventricular anastomosis are no longer commercially available. We described the technique that we performed on a 60-year-old patient with readily available material.
Primary cardiac lymphomas (PCLs) are rare in immunocompetent patients. Their clinical presentation is highly variable and in case of cardiogenic shock, death is often inevitable with a diagnosis made ...post-mortem. We report the case of a 65-year old immunocompetent man with cardiogenic shock requiring emergent extracorporeal membrane oxygenation (ECMO). Soon after, a diagnosis of PCL was given and chemotherapy was delivered under ECMO support. The patient was progressively weaned from the mechanical support. Six months later, he had fully recovered.
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