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Scientific Reports Aug 2023We hypothesized that the association between BP and endovascular treatment (EVT) outcomes would differ by baseline perfusion and recanalization status. We identified 388...
We hypothesized that the association between BP and endovascular treatment (EVT) outcomes would differ by baseline perfusion and recanalization status. We identified 388 ICA or M1 occlusion patients who underwent EVT ≤ 24 h from onset with successful recanalization (TICI ≥ 2b). BP was measured at 5-min intervals from arrival and during the procedure. Systolic BPs (SBP) were summarized as dropmax (the maximal decrease over two consecutive measurements), incmax (the maximal increase), mean, coefficient of variation (cv), and standard deviation. Adequate baseline perfusion was defined as hypoperfusion intensity ratio (HIR) ≤ 0.5; infarct proportion as the volume ratio of final infarcts within the T > 6 s region. In the adequate perfusion group, infarct proportion was closely associated with SBP (β ± SE (P-value); 1.22 ± 0.48, (< 0.01)), SBP (1.12 ± 0.33, (< 0.01)), SBP (0.61 ± 0.15 (< 0.01)), SBP (0.66 ± 0.08 (< 0.01)), and SBP (0.71 ± 0.37 (0.053) before recanalization. The associations remained significant only in SBP, SBP, and SBP after recanalization. SBP, SBP and SBP showed significant associations with modified Rankin Scale score at 3 months in the pre-recanalization period. In the poor perfusion group, none of the SBP indices was associated with any stroke outcomes regardless of recanalization status. BP may show differential associations with stroke outcomes by the recanalization and baseline perfusion status.
Topics: Humans; Blood Pressure; Perfusion; Reperfusion; Stroke; Treatment Outcome
PubMed: 37612355
DOI: 10.1038/s41598-023-40572-0 -
Frontiers in Immunology 2023In response to the increasing demand for lung transplantation, lung perfusion (EVLP) has extended the number of suitable donor lungs by rehabilitating marginal organs....
In response to the increasing demand for lung transplantation, lung perfusion (EVLP) has extended the number of suitable donor lungs by rehabilitating marginal organs. However despite an expanding use in clinical practice, the responses of the different lung cell types to EVLP are not known. In order to advance our mechanistic understanding and establish a refine tool for improvement of EVLP, we conducted a pioneer study involving single cell RNA-seq on human lungs declined for transplantation. Functional enrichment analyses were performed upon integration of data sets generated at 4 h (clinical duration) and 10 h (prolonged duration) from two human lungs processed to EVLP. Pathways related to inflammation were predicted activated in epithelial and blood endothelial cells, in monocyte-derived macrophages and temporally at 4 h in alveolar macrophages. Pathways related to cytoskeleton signaling/organization were predicted reduced in most cell types mainly at 10 h. We identified a division of labor between cell types for the selected expression of cytokine and chemokine genes that varied according to time. Immune cells including CD4 and CD8 T cells, NK cells, mast cells and conventional dendritic cells displayed gene expression patterns indicating blunted activation, already at 4 h in several instances and further more at 10 h. Therefore despite inducing inflammatory responses, EVLP appears to dampen the activation of major lung immune cell types, what may be beneficial to the outcome of transplantation. Our results also support that therapeutics approaches aiming at reducing inflammation upon EVLP should target both the alveolar and vascular compartments.
Topics: Humans; Perfusion; CD8-Positive T-Lymphocytes; Endothelial Cells; Lung Transplantation; Lung; Inflammation
PubMed: 37465668
DOI: 10.3389/fimmu.2023.1142228 -
Frontiers in Immunology 2022Transplant centers around the world have been using extended criteria donors to remedy the ongoing demand for lung transplantation. With a rapidly aging population,... (Review)
Review
Transplant centers around the world have been using extended criteria donors to remedy the ongoing demand for lung transplantation. With a rapidly aging population, older donors are increasingly considered. Donor age, at the same time has been linked to higher rates of lung ischemia reperfusion injury (IRI). This process of acute, sterile inflammation occurring upon reperfusion is a key driver of primary graft dysfunction (PGD) leading to inferior short- and long-term survival. Understanding and improving the condition of older lungs is thus critical to optimize outcomes. Notably, lung perfusion (EVLP) seems to have the potential of reconditioning ischemic lungs through perfusing and ventilation. Here, we aim to delineate mechanisms driving lung IRI and review both experimental and clinical data on the effects of aging in augmenting the consequences of IRI and PGD in lung transplantation.
Topics: Aged; Humans; Lung; Perfusion; Primary Graft Dysfunction; Reperfusion Injury
PubMed: 35686120
DOI: 10.3389/fimmu.2022.891564 -
Science Advances Dec 2023Proper placental vascularization is vital for pregnancy outcomes, but assessing it with animal models and human explants has limitations. We introduce a 3D in vitro...
Proper placental vascularization is vital for pregnancy outcomes, but assessing it with animal models and human explants has limitations. We introduce a 3D in vitro model of human placenta terminal villi including fetal mesenchyme and vascular endothelium. By coculturing HUVEC, placental fibroblasts, and pericytes in a macrofluidic chip with a flow reservoir, we generate fully perfusable fetal microvessels. Pressure-driven flow facilitates microvessel growth and remodeling, resulting in early formation of interconnected and lasting placental-like vascular networks. Computational fluid dynamics simulations predict shear forces, which increase microtissue stiffness, decrease diffusivity, and enhance barrier function as shear stress rises. Mass spectrometry analysis reveals enhanced protein expression with flow, including matrix stability regulators, proteins associated with actin dynamics, and cytoskeleton organization. Our model provides a powerful tool for deducing complex in vivo parameters, such as shear stress on developing vascularized placental tissue, and holds promise for unraveling gestational disorders related to the vasculature.
Topics: Animals; Pregnancy; Humans; Female; Placenta; Perfusion; Neovascularization, Pathologic; Coculture Techniques; Microvessels
PubMed: 38134282
DOI: 10.1126/sciadv.adj8540 -
Transplant International : Official... Jun 2015Kidney transplantation is limited by hypothermic preservation techniques. Prolonged periods of cold ischaemia increase the risk of early graft dysfunction and reduce... (Review)
Review
Kidney transplantation is limited by hypothermic preservation techniques. Prolonged periods of cold ischaemia increase the risk of early graft dysfunction and reduce long-term survival. To extend the boundaries of transplantation and utilize kidneys from more marginal donors, improved methods of preservation are required. Normothermic perfusion restores energy levels in the kidney allowing renal function to be restored ex vivo. This has several advantages: cold ischaemic injury can be avoided or minimized, the kidney can be maintained in a stable state allowing close observation and assessment of viability and lastly, it provides the ideal opportunity to add therapies to directly manipulate and improve the condition of the kidney. This review explores the experimental and clinical evidence for ex vivo normothermic perfusion in kidney transplantation and its role in conditioning and repair.
Topics: Cold Ischemia; Donor Selection; Genetic Therapy; Humans; Ischemia; Kidney; Kidney Transplantation; Organ Preservation; Organ Preservation Solutions; Perfusion; Stem Cell Transplantation; Temperature; Tissue Donors; Transplantation Conditioning
PubMed: 24629095
DOI: 10.1111/tri.12319 -
Frontiers in Immunology 2022Normothermic machine perfusion (NMP) allows viability assessment and potential resuscitation of donor livers prior to transplantation. The immunological effect of NMP on...
BACKGROUND
Normothermic machine perfusion (NMP) allows viability assessment and potential resuscitation of donor livers prior to transplantation. The immunological effect of NMP on liver allografts is undetermined, with potential implications on allograft function, rejection outcomes and overall survival. In this study we define the changes in immune profile of human livers during NMP.
METHODS
Six human livers were placed on a NMP device. Tissue and perfusate samples were obtained during cold storage prior to perfusion and at 1, 3, and 6 hours of perfusion. Flow cytometry, immunohistochemistry, and bead-based immunoassays were used to measure leukocyte composition and cytokines in the perfusate and within the liver tissue. Mean values between baseline and time points were compared by Student's t-test.
RESULTS
Within circulating perfusate, significantly increased frequencies of CD4 T cells, B cells and eosinophils were detectable by 1 hour of NMP and continued to increase at 6 hours of perfusion. On the other hand, NK cell frequency significantly decreased by 1 hour of NMP and remained decreased for the duration of perfusion. Within the liver tissue there was significantly increased B cell frequency but decreased neutrophils detectable at 6 hours of NMP. A transient decrease in intermediate monocyte frequency was detectable in liver tissue during the middle of the perfusion run. Overall, no significant differences were detectable in tissue resident T regulatory cells during NMP. Significantly increased levels of pro-inflammatory and anti-inflammatory cytokines were seen following initiation of NMP that continued to rise throughout duration of perfusion.
CONCLUSIONS
Time-dependent dynamic changes are seen in individual leukocyte cell-types within both perfusate and tissue compartments of donor livers during NMP. This suggests a potential role of NMP in altering the immunogenicity of donor livers prior to transplant. These data also provide insights for future work to recondition the intrinsic immune profile of donor livers during NMP prior to transplantation.
Topics: Cytokines; Humans; Liver; Liver Transplantation; Living Donors; Organ Preservation; Perfusion
PubMed: 35720395
DOI: 10.3389/fimmu.2022.788935 -
Acta Neuropathologica Communications Sep 2019Perfusing fixatives through the cerebrovascular system is the gold standard approach in animals to prepare brain tissue for spatial biomolecular profiling, circuit... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Perfusing fixatives through the cerebrovascular system is the gold standard approach in animals to prepare brain tissue for spatial biomolecular profiling, circuit tracing, and ultrastructural studies such as connectomics. Translating these discoveries to humans requires examination of postmortem autopsy brain tissue. Yet banked brain tissue is routinely prepared using immersion fixation, which is a significant barrier to optimal preservation of tissue architecture. The challenges involved in adopting perfusion fixation in brain banks and the extent to which it improves histology quality are not well defined.
METHODOLOGY
We searched four databases to identify studies that have performed perfusion fixation in human brain tissue and screened the references of the eligible studies to identify further studies. From the included studies, we extracted data about the methods that they used, as well as any data comparing perfusion fixation to immersion fixation. The protocol was preregistered at the Open Science Framework: https://osf.io/cv3ys/ .
RESULTS
We screened 4489 abstracts, 214 full-text publications, and identified 35 studies that met our inclusion criteria, which collectively reported on the perfusion fixation of 558 human brains. We identified a wide variety of approaches to perfusion fixation, including perfusion fixation of the brain in situ and ex situ, perfusion fixation through different sets of blood vessels, and perfusion fixation with different washout solutions, fixatives, perfusion pressures, and postfixation tissue processing methods. Through a qualitative synthesis of data comparing the outcomes of perfusion and immersion fixation, we found moderate confidence evidence showing that perfusion fixation results in equal or greater subjective histology quality compared to immersion fixation of relatively large volumes of brain tissue, in an equal or shorter amount of time.
CONCLUSIONS
This manuscript serves as a resource for investigators interested in building upon the methods and results of previous research in designing their own perfusion fixation studies in human brains or other large animal brains. We also suggest several future research directions, such as comparing the in situ and ex situ approaches to perfusion fixation, studying the efficacy of different washout solutions, and elucidating the types of brain donors in which perfusion fixation is likely to result in higher fixation quality than immersion fixation.
Topics: Brain; Humans; Perfusion; Tissue Banks; Tissue Fixation
PubMed: 31488214
DOI: 10.1186/s40478-019-0799-y -
The Journal of Surgical Research Feb 2022Machine perfusion is gaining interest as an efficient method of tissue preservation of Vascularized Composite Allografts (VCA). The aim of this study was to develop a...
BACKGROUND
Machine perfusion is gaining interest as an efficient method of tissue preservation of Vascularized Composite Allografts (VCA). The aim of this study was to develop a protocol for ex vivo subnormothermic oxygenated machine perfusion (SNMP) on rodent hindlimbs and to validate our protocol in a heterotopic hindlimb transplant model.
METHODS
In this optimization study we compared three different solutions during 6 h of SNMP (n = 4 per group). Ten control limbs were stored in a preservation solution on Static Cold Storage [SCS]). During SNMP we monitored arterial flowrate, lactate levels, and edema. After SNMP, muscle biopsies were taken for histology examination, and energy charge analysis. We validated the best perfusion protocol in a heterotopic limb transplantation model with 30-d follow up (n = 13). As controls, we transplanted untreated limbs (n = 5) and hindlimbs preserved with either 6 or 24 h of SCS (n = 4 and n = 5).
RESULTS
During SNMP, arterial outflow increased, and lactate clearance decreased in all groups. Total edema was significantly lower in the HBOC-201 group compared to the BSA group (P = 0.005), 4.9 (4.3-6.1) versus 48.8 (39.1-53.2) percentage, but not to the BSA + PEG group (P = 0.19). Energy charge levels of SCS controls decreased 4-fold compared to limbs perfused with acellular oxygen carrier HBOC-201, 0.10 (0.07-0.17) versus 0.46 (0.42-0.49) respectively (P = 0.002).
CONCLUSIONS
Six hours ex vivo SNMP of rodent hindlimbs using an acellular oxygen carrier HBOC-201 results in superior tissue preservation compared to conventional SCS.
Topics: Allografts; Animals; Composite Tissue Allografts; Extremities; Organ Preservation; Oxygen; Perfusion
PubMed: 34670191
DOI: 10.1016/j.jss.2021.09.005 -
The Journal of Thoracic and... Feb 2016
Topics: Animals; Hemofiltration; Lung; Perfusion; Pulmonary Edema
PubMed: 26232315
DOI: 10.1016/j.jtcvs.2015.06.055 -
Transplant International : Official... 2023Pancreas transplantation is the only curative treatment for patients with complicated diabetes, and organ shortage is a common and increasing problem. Strategies to...
Pancreas transplantation is the only curative treatment for patients with complicated diabetes, and organ shortage is a common and increasing problem. Strategies to expand the donor pool are needed, and normothermic perfusion of the pancreas has the potential to test and repair grafts before implantation. Between January 2021 and April 2022, six human pancreases, declined for transplantation or islet isolation, were perfused using a previously established method by our group. All 6 cases were successfully perfused for 4 h, with minimal edema. The mean age of the donors was 44.16 ± 13.8 years. Five grafts were obtained from neurological death donors, and one was obtained from a donation after cardiac death. The mean glucose and lactate levels decreased throughout perfusion and insulin levels increased. All 6 grafts were metabolically active during perfusion and histopathology showed minimal tissue injury and no edema. Human normothermic perfusion of the pancreas is feasible and safe and has the potential to expand the donor pool. Future studies will focus on tests and biomarkers for the assessment of grafts.
Topics: Humans; Adult; Middle Aged; Organ Preservation; Feasibility Studies; Perfusion; Tissue Donors; Pancreas; Allografts
PubMed: 37252614
DOI: 10.3389/ti.2023.10936