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Biotechnology and Bioengineering Mar 2020Natural tissues are incorporated with vasculature, which is further integrated with a cardiovascular system responsible for driving perfusion of nutrient-rich oxygenated...
Natural tissues are incorporated with vasculature, which is further integrated with a cardiovascular system responsible for driving perfusion of nutrient-rich oxygenated blood through the vasculature to support cell metabolism within most cell-dense tissues. Since scaffold-free biofabricated tissues being developed into clinical implants, research models, and pharmaceutical testing platforms should similarly exhibit perfused tissue-like structures, we generated a generalizable biofabrication method resulting in self-supporting perfused (SSuPer) tissue constructs incorporated with perfusible microchannels and integrated with the modular FABRICA perfusion bioreactor. As proof of concept, we perfused an MLO-A5 osteoblast-based SSuPer tissue in the FABRICA. Although our resulting SSuPer tissue replicated vascularization and perfusion observed in situ, supported its own weight, and stained positively for mineral using Von Kossa staining, our in vitro results indicated that computational fluid dynamics (CFD) should be used to drive future construct design and flow application before further tissue biofabrication and perfusion. We built a CFD model of the SSuPer tissue integrated in the FABRICA and analyzed flow characteristics (net force, pressure distribution, shear stress, and oxygen distribution) through five SSuPer tissue microchannel patterns in two flow directions and at increasing flow rates. Important flow parameters include flow direction, fully developed flow, and tissue microchannel diameters matched and aligned with bioreactor flow channels. We observed that the SSuPer tissue platform is capable of providing direct perfusion to tissue constructs and proper culture conditions (oxygenation, with controllable shear and flow rates), indicating that our approach can be used to biofabricate tissue representing primary tissues and that we can model the system in silico.
Topics: Animals; Bioprinting; Bioreactors; Cell Line; Computer Simulation; Equipment Design; Hydrodynamics; Mice; Models, Biological; Osteoblasts; Perfusion
PubMed: 31788785
DOI: 10.1002/bit.27238 -
Critical Care (London, England) May 2020Microcirculatory perfusion disturbances are associated with increased morbidity and mortality in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB)....
BACKGROUND
Microcirculatory perfusion disturbances are associated with increased morbidity and mortality in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Technological advancements made it possible to monitor sublingual microcirculatory perfusion over time. The goal of this review is to provide an overview of the course of alterations in sublingual microcirculatory perfusion following CPB. The secondary goal is to identify which parameter of sublingual microcirculatory perfusion is most profoundly affected by CPB.
METHODS
PubMed and Embase databases were systematically searched according to PRISMA guidelines and as registered in PROSPERO. Studies that reported sublingual microcirculatory perfusion measurements before and after onset of CPB in adult patients undergoing cardiac surgery were included. The primary outcome was sublingual microcirculatory perfusion, represented by functional capillary density (FCD), perfused vessel density (PVD), total vessel density (TVD), proportion of perfused vessels (PPV), and microvascular flow index (MFI).
RESULTS
The search identified 277 studies, of which 19 fulfilled all eligibility criteria. Initiation of CPB had a profound effect on FCD, PVD, or PPV. Seventeen studies (89%) reported one or more of these parameters, and in 11 of those studies (65%), there was a significant decrease in these parameters during cardiac surgery; the other 6 studies (35%) reported no effect. In 29% of the studies, FCD, PVD, or PPV normalized by the end of cardiac surgery, and in 24% percent of the studies, this effect lasted at least 24 h. There was no clear effect of CPB on TVD and a mixed effect on MFI.
CONCLUSION
CPB during cardiac surgery impaired sublingual microcirculatory perfusion as reflected by reduced FCD, PVD, and PPV. Four studies reported this effect at least 24 h after surgery. Further research is warranted to conclude on the duration of CPB-induced microcirculatory perfusion disturbances and the relationship with clinical outcome.
TRIAL REGISTRATION
PROSPERO, CRD42019127798.
Topics: Adult; Cardiopulmonary Bypass; Female; Humans; Male; Microcirculation; Middle Aged; Perfusion; Postoperative Complications
PubMed: 32404120
DOI: 10.1186/s13054-020-02948-w -
Minerva Anestesiologica Feb 2018This review focuses on recent developments in preservation techniques in liver transplantation. First, we discuss mechanisms of organ injury when using high-risk organs,... (Review)
Review
This review focuses on recent developments in preservation techniques in liver transplantation. First, we discuss mechanisms of organ injury when using high-risk organs, including donation after circulatory death and steatotic grafts and we summarize pathways of ischemia reperfusion injury together with their link to the immune response. Second, we report on improvement strategies of marginal liver grafts by different machine perfusion concepts and summarize perfusion approaches with recent clinical implementation.
Topics: Humans; Liver Transplantation; Perfusion; Postoperative Complications; Preoperative Care
PubMed: 28726360
DOI: 10.23736/S0375-9393.17.12016-X -
Transplant International : Official... 2023Normothermic machine perfusion (NMP) has reshaped organ preservation in recent years. In this preclinical study, prolonged normothermic perfusions of discarded human...
Normothermic machine perfusion (NMP) has reshaped organ preservation in recent years. In this preclinical study, prolonged normothermic perfusions of discarded human kidney grafts were performed in order to investigate perfusion dynamics and identify potential quality and assessment indicators. Five human discarded kidney grafts were perfused normothermically (37°C) for 48 h using the Kidney Assist device with a red-blood-cell based perfusate with urine recirculation. Perfusion dynamics, perfusate and urine composition as well as injury markers were measured and analyzed. Donor age ranged from 41 to 68 years. All but one kidney were from brain dead donors. Perfusions were performed successfully for 48 h with all discarded kidneys. Median arterial flow ranged from 405 to 841 mL/min. All kidneys excreted urine until the end of perfusion (median 0.43 mL/min at the end of perfusion). While sodium levels were consistently lower in urine compared to perfusate samples, this was only seen for chloride and potassium in kidney KTX 2. Lactate, AST, LDH as well as pro-inflammatory cytokines increased over time, especially in kidneys KTX 3 and 4. normothermic perfusion is able to identify patterns of perfusion, biological function, and changes in inflammatory markers in heterogenous discarded kidney grafts.
Topics: Humans; Adult; Middle Aged; Aged; Kidney; Kidney Transplantation; Perfusion; Organ Preservation; Extracorporeal Circulation
PubMed: 37901298
DOI: 10.3389/ti.2023.11804 -
The Journal of Thoracic and... Feb 2021Improvement in ex vivo lung perfusion protocols could increase the number of donors available for transplantation and protect the lungs from primary graft dysfunction....
OBJECTIVE
Improvement in ex vivo lung perfusion protocols could increase the number of donors available for transplantation and protect the lungs from primary graft dysfunction. We hypothesize that perfusate adsorption during ex vivo lung perfusion reconditions the allograft to ischemia-reperfusion injury after lung transplantation.
METHODS
Donor pig lungs were preserved for 24 hours at 4°C, followed by 6 hours of ex vivo lung perfusion according to the Toronto protocol. The perfusate was additionally adsorbed through a CytoSorb adsorber (CytoSorbents, Berlin, Germany) in the treatment group, whereas control lungs were perfused according to the standard protocol (n = 5, each). Ex vivo lung perfusion physiology and biochemistry were monitored. Upon completion of ex vivo lung perfusion, a left single lung transplantation was performed. Oxygenation function and lung mechanics were assessed during a 4-hour reperfusion period. The inflammatory response was determined during ex vivo lung perfusion and reperfusion.
RESULTS
The cytokine concentrations in the perfusate were markedly lower with the adsorber, resulting in improved ex vivo lung perfusion physiology and biochemistry during the 6-hour perfusion period. Post-transplant dynamic lung compliance was markedly better during the 4-hour reperfusion period in the treatment group. Isolated allograft oxygenation function and dynamic compliance continued to be superior in the adsorber group at the end of reperfusion, accompanied by a markedly decreased local inflammatory response.
CONCLUSIONS
Implementation of an additional cytokine adsorber has refined the standard ex vivo lung perfusion protocol. Furthermore, cytokine removal during ex vivo lung perfusion improved immediate post-transplant graft function together with a less intense inflammatory response to reperfusion in pigs. Further studies are warranted to understand the beneficial effects of perfusate adsorption during ex vivo lung perfusion in the clinical setting.
Topics: Adsorption; Animals; Cytokines; Female; Humans; Lung; Lung Transplantation; Meropenem; Methylprednisolone; Perfusion; Swine; Treatment Outcome
PubMed: 32201002
DOI: 10.1016/j.jtcvs.2019.12.128 -
Transplant International : Official... Jun 2015Hypothermic machine perfusion (HMP) of kidneys is a long-established alternative to static cold storage and has been suggested to be a better preservation method. Today,... (Review)
Review
Hypothermic machine perfusion (HMP) of kidneys is a long-established alternative to static cold storage and has been suggested to be a better preservation method. Today, as our deceased donor profile continues to change towards higher-risk kidneys of lower quality, we are confronted with the limits of cold storage. Interest in HMP as a preservation technique is on the rise. Furthermore, HMP also creates a window of opportunity during which to assess the viability and quality of the graft before transplantation. The technology might also provide a platform during which the graft could be actively repaired, making it particularly attractive for higher-risk kidneys. We review the current evidence on HMP in kidney transplantation and provide an outlook for the use of the technology in the years to come.
Topics: Cold Temperature; Donor Selection; Drug Delivery Systems; Genetic Therapy; Graft Survival; Humans; Kidney Transplantation; Organ Preservation; Organ Preservation Solutions; Oxygen; Perfusion; Randomized Controlled Trials as Topic; Stem Cell Transplantation; Tissue Donors; Treatment Outcome
PubMed: 25630347
DOI: 10.1111/tri.12530 -
Transplant International : Official... 2022normothermic perfusion (EVNP) is an emerging strategy in kidney preservation that enables resuscitation and viability assessment under pseudo-physiological conditions... (Review)
Review
normothermic perfusion (EVNP) is an emerging strategy in kidney preservation that enables resuscitation and viability assessment under pseudo-physiological conditions prior to transplantation. The optimal perfusate composition and duration, however, remain undefined. A systematic literature search (Embase; Medline; Scopus; and BIOSIS Previews) was conducted. We identified 1,811 unique articles dating from January 1956 to July 2021, from which 24 studies were deemed eligible for qualitative analysis. The perfusate commonly used in clinical practice consisted of leukocyte-depleted, packed red blood cells suspended in Ringer's lactate solution with Mannitol, dexamethasone, heparin, sodium bicarbonate and a specific nutrient solution supplemented with insulin, glucose, multivitamins and vasodilators. There is increasing support in preclinical studies for non-blood cell-based perfusates, including Steen solution, synthetic haem-based oxygen carriers and acellular perfusates with supraphysiological carbogen mixtures that support adequate oxygenation whilst also enabling gradual rewarming. Extended durations of perfusion (up to 24 h) were also feasible in animal models. Direct comparison between studies was not possible due to study heterogeneity. Current evidence demonstrates safety with the aforementioned widely used protocol, however, extracellular base solutions with adequate oxygenation, supplemented with nutrient and metabolic substrates, show promise by providing a suitable environment for prolonged preservation and resuscitation. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021231381, identifier PROSPERO 2021 CRD42021231381.
Topics: Animals; Extracorporeal Circulation; Humans; Kidney; Kidney Transplantation; Organ Preservation; Perfusion
PubMed: 35634582
DOI: 10.3389/ti.2022.10236 -
Transplantation Jun 2023Deceased donor livers are prone to biliary complications, which may necessitate retransplantation, and we, and others, have suggested that these complications are...
D-dimer Release From Livers During Ex Situ Normothermic Perfusion and After In Situ Normothermic Regional Perfusion: Evidence for Occult Fibrin Burden Associated With Adverse Transplant Outcomes and Cholangiopathy.
BACKGROUND
Deceased donor livers are prone to biliary complications, which may necessitate retransplantation, and we, and others, have suggested that these complications are because of peribiliary vascular fibrin microthrombi. We sought to determine the prevalence and consequence of occult fibrin within deceased donor livers undergoing normothermic ex situ perfusion (NESLiP) and evaluate a role for fibrinolysis.
METHODS
D-dimer concentrations, products of fibrin degradation, were assayed in the perfusate of 163 livers taken after 2 h of NESLiP, including 91 that were transplanted. These were related to posttransplant outcomes. Five different fibrinolytic protocols during NESLiP using alteplase were evaluated, and the transplant outcomes of these alteplase-treated livers were reviewed.
RESULTS
Perfusate D-dimer concentrations were lowest in livers recovered using in situ normothermic regional perfusion and highest in alteplase-treated livers. D-dimer release from donation after brain death livers was significantly correlated with the duration of cold ischemia. In non-alteplase-treated livers, Cox proportional hazards regression analysis showed that D-dimer levels were associated with transplant survival ( P = 0.005). Treatment with alteplase and fresh frozen plasma during NESLiP was associated with significantly more D-dimer release into the perfusate and was not associated with excess bleeding postimplantation; 8 of the 9 treated livers were free of cholangiopathy, whereas the ninth had a proximal duct stricture.
CONCLUSIONS
Fibrin is present in many livers during cold storage and is associated with poor posttransplant outcomes. The amount of D-dimer released after fibrinolytic treatment indicates a significant occult fibrin burden and suggests that fibrinolytic therapy during NESLiP may be a promising therapeutic intervention.
Topics: Humans; Liver Transplantation; Fibrin; Organ Preservation; Liver; Perfusion
PubMed: 36728501
DOI: 10.1097/TP.0000000000004475 -
Scandinavian Journal of Trauma,... Dec 2023Selective aortic arch perfusion (SAAP) is a novel endovascular technique that combines thoracic aortic occlusion with extracorporeal perfusion of the brain and heart....
BACKGROUND
Selective aortic arch perfusion (SAAP) is a novel endovascular technique that combines thoracic aortic occlusion with extracorporeal perfusion of the brain and heart. SAAP may have a role in both haemorrhagic shock and in cardiac arrest due to coronary ischaemia. Despite promising animal studies, no data is available that describes SAAP in humans. The primary aim of this study was to assess the feasibility of selective aortic arch perfusion in humans. The secondary aim of the study was to assess the feasibility of achieving direct coronary artery access via the SAAP catheter as a potential conduit for salvage percutaneous coronary intervention.
METHODS
Using perfused human cadavers, a prototype SAAP catheter was inserted into the descending aorta under fluoroscopic guidance via a standard femoral percutaneous access device. The catheter balloon was inflated and the aortic arch perfused with radio-opaque contrast. The coronary arteries were cannulated through the SAAP catheter.
RESULTS
The procedure was conducted four times. During the first two trials the SAAP catheter was passed rapidly and without incident to the intended descending aortic landing zone and aortic arch perfusion was successfully delivered via the device. The SAAP catheter balloon failed on the third trial. On the fourth trial the left coronary system was cannulated using a 5Fr coronary guiding catheter through the central SAAP catheter lumen.
CONCLUSIONS
For the first time using a perfused cadaveric model we have demonstrated that a SAAP catheter can be easily and safely inserted and SAAP can be achieved using conventional endovascular techniques. The SAAP catheter allowed successful access to the proximal aorta and permitted retrograde perfusion of the coronary and cerebral circulation.
Topics: Humans; Aorta; Aorta, Thoracic; Heart Arrest; Perfusion; Shock, Hemorrhagic; Feasibility Studies
PubMed: 38087352
DOI: 10.1186/s13049-023-01148-z -
The Journal of Thoracic and... Feb 2021
Topics: Adsorption; Extracorporeal Circulation; Humans; Lung; Perfusion; Seasons
PubMed: 31959447
DOI: 10.1016/j.jtcvs.2019.12.012