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BioMed Research International 2015Arch surgery remains undoubtedly among the most technically and strategically challenging endeavors in cardiovascular surgery. Surgical interventions of thoracic... (Review)
Review
Arch surgery remains undoubtedly among the most technically and strategically challenging endeavors in cardiovascular surgery. Surgical interventions of thoracic aneurysms involving the aortic arch require complete circulatory arrest in deep hypothermia (DHCA) or elaborate cerebral perfusion strategies with varying degrees of hypothermia to achieve satisfactory protection of the brain from ischemic insults, that is, unilateral/bilateral antegrade cerebral perfusion (ACP) and retrograde cerebral perfusion (RCP). Despite sophisticated and increasingly individualized surgical approaches for complex aortic pathologies, there remains a lack of consensus regarding the optimal method of cerebral protection and circulatory management during the time of arch exclusion. Many recent studies argue in favor of ACP with various degrees of hypothermic arrest during arch reconstruction and its advantages have been widely demonstrated. In fact ACP with more moderate degrees of hypothermia represents a paradigm shift in the cardiac surgery community and is widely adopted as an emergent strategy; however, many centers continue to report good results using other perfusion strategies. Amidst this important discussion we review currently available surgical strategies of cerebral protection management and compare the results of recent European multicenter and single-center data.
Topics: Aorta; Aorta, Thoracic; Aortic Aneurysm, Thoracic; Cerebrovascular Circulation; Circulatory Arrest, Deep Hypothermia Induced; Hospital Mortality; Humans; Perfusion; Risk Factors; Treatment Outcome
PubMed: 26713319
DOI: 10.1155/2015/981813 -
ACS Nano Nov 2021Targeted delivery of therapeutics through the use of nanoparticles (NPs) has emerged as a promising method that increases their efficacy and reduces their side effects.... (Review)
Review
Targeted delivery of therapeutics through the use of nanoparticles (NPs) has emerged as a promising method that increases their efficacy and reduces their side effects. NPs can be tailored to localize to selective tissues through conjugation to ligands that bind cell-specific receptors. Although the vast majority of nanodelivery platforms have focused on cancer therapy, efforts have begun to introduce nanotherapeutics to the fields of immunology as well as transplantation. In this review, we provide an overview from a clinician's perspective of current nanotherapeutic strategies to treat solid organ transplants with NPs during the time interval between organ harvest from the donor and placement into the recipient, an innovative technology that can provide major benefits to transplant patients. The use of normothermic machine perfusion (NMP), which is associated with preserving the function of the organ following transplantation, also provides an ideal opportunity for a localized, sustained, and controlled delivery of nanotherapeutics to the organ during this critical time period. Here, we summarize previous endeavors to improve transplantation outcomes by treating the organ with NPs prior to placement in the recipient. Investigations in this burgeoning field of research are promising, but more extensive studies are needed to overcome the physiological challenges to achieving effective nanotherapeutic delivery to transplanted organs discussed in this review.
Topics: Humans; Organ Preservation; Perfusion; Transplants; Organ Transplantation
PubMed: 34714050
DOI: 10.1021/acsnano.1c04707 -
International Journal of Molecular... Sep 2020Acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality, and current management has a dramatic impact on healthcare resource... (Review)
Review
Acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality, and current management has a dramatic impact on healthcare resource utilization. While our understanding of this disease has improved, the majority of treatment strategies remain supportive in nature and are associated with continued poor outcomes. There is a dramatic need for the development and breakthrough of new methods for the treatment of ARDS. Isolated machine lung perfusion is a promising surgical platform that has been associated with the rehabilitation of injured lungs and the induction of molecular and cellular changes in the lung, including upregulation of anti-inflammatory and regenerative pathways. Initially implemented in an ex vivo fashion to evaluate marginal donor lungs prior to transplantation, recent investigations of isolated lung perfusion have shifted in vivo and are focused on the management of ARDS. This review presents current tenants of ARDS management and isolated lung perfusion, with a focus on how ex vivo lung perfusion (EVLP) has paved the way for current investigations utilizing in vivo lung perfusion (IVLP) in the treatment of severe ARDS.
Topics: Animals; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Inflammation; Lung Injury; Perfusion; Respiratory Distress Syndrome; Tissue Donors
PubMed: 32957547
DOI: 10.3390/ijms21186820 -
Kidney International Apr 2023Although hypothermic machine perfusion (HMP) is associated with improved kidney graft viability and function, the underlying biological mechanisms are unknown....
Although hypothermic machine perfusion (HMP) is associated with improved kidney graft viability and function, the underlying biological mechanisms are unknown. Untargeted metabolomic profiling may identify potential metabolites and pathways that can help assess allograft viability and contribute to organ preservation. Therefore, in this multicenter study, we measured all detectable metabolites in perfusate collected at the beginning and end of deceased-donor kidney perfusion and evaluated their associations with graft failure. In our cohort of 190 kidney transplants, 33 (17%) had death-censored graft failure over a median follow-up of 5.0 years (IQR 3.0-6.1 years). We identified 553 known metabolites in perfusate and characterized their experimental and biological consistency through duplicate samples and unsupervised clustering. After perfusion-time adjustment and false discovery correction, six metabolites in post-HMP perfusate were significantly associated with death-censored graft failure, including alpha-ketoglutarate, 3-carboxy-4-methyl-5-propyl-2-furanpropanoate, 1-carboxyethylphenylalanine, and three glycerol-phosphatidylcholines. All six metabolites were associated with an increased risk of graft failure (Hazard Ratio per median absolute deviation range 1.04-1.45). Four of six metabolites also demonstrated significant interaction with donation after cardiac death with notably greater risk in the donation after cardiac death group (Hazard Ratios up to 1.69). Discarded kidneys did not have significantly different levels of any death-censored graft failure-associated metabolites. On interrogation of pathway analysis, production of reactive oxygen species and increased metabolism of fatty acids were upregulated in kidneys that subsequently developed death-censored graft failure. Thus, further understanding the role of these metabolites may inform the HMP process and help improve the objective evaluation of allograft offers, thereby reducing the discard of potentially viable organs.
Topics: Humans; Kidney; Kidney Transplantation; Perfusion; Tissue Donors; Death; Allografts; Graft Survival
PubMed: 36549364
DOI: 10.1016/j.kint.2022.11.020 -
PloS One 2021Normothermic machine perfusion (NMP) of donor kidneys provides the opportunity for improved graft preservation and objective pre-transplant ex-vivo organ assessment....
Normothermic machine perfusion (NMP) of donor kidneys provides the opportunity for improved graft preservation and objective pre-transplant ex-vivo organ assessment. Currently, a multitude of perfusion solutions exist for renal NMP. This study aimed to evaluate four different perfusion solutions side-by-side and determine the influence of different perfusate compositions on measured renal perfusion parameters. Porcine kidneys and blood were obtained from a slaughterhouse. Kidneys underwent NMP at 37°C for 7 hours, with 4 different perfusion solutions (n = 5 per group). Group 1 consisted of red blood cells (RBCs) and a perfusion solution based on Williams' Medium E. Group 2 consisted of RBCs, albumin and a balanced electrolyte composition. Group 3 contained RBCs and a medium based on a British clinical NMP solution. Group 4 contained RBCs and a medium used in 24-hour perfusion experiments. NMP flow patterns for solutions 1 and 2 were similar, solutions 3 and 4 showed lower but more stable flow rates. Thiobarbituric acid reactive substances were significantly higher in solution 1 and 4 compared to the other groups. Levels of injury marker N-acetyl-β-D glucosaminidase were significantly lower in solution 2 in comparison with solution 3 and 4. This study illustrates that the perfusate composition during NMP significantly impacts the measured perfusion and injury parameters and thus affects the interpretation of potential viability markers. Further research is required to investigate the individual influences of principal perfusate components to determine the most optimal conditions during NMP and eventually develop universal organ assessment criteria.
Topics: Animals; Kidney; Kidney Transplantation; Organ Preservation; Perfusion; Swine
PubMed: 34003874
DOI: 10.1371/journal.pone.0251595 -
American Journal of Veterinary Research Dec 2023To evaluate skin perfusion in cats receiving dexmedetomidine compared to a placebo.
OBJECTIVE
To evaluate skin perfusion in cats receiving dexmedetomidine compared to a placebo.
ANIMALS
9 healthy adult research cats.
METHODS
A randomized, blinded, placebo-controlled study design was used. Two sites, the dorsal metatarsus (site: limb) and lateral flank (site: flank), were evaluated with laser speckle contrast imaging (LSCI) at baseline and following administration of dexmedetomidine (1, 3, or 5 mcg/kg, IV) or a placebo (0.9% saline, IV). Mean speckle contrast (MSC), a surrogate for perfusion, was obtained from LSCI and compared between treatments. Heart rate, sedation score, and body temperature were recorded. Skin perfusion to the flank and limb, reported as MSC, was assessed via LSCI at baseline and at 5, 10, and 15 minutes posttreatment.
RESULTS
There was a significant decrease in heart rate (P < .001) in cats receiving 1, 3, and 5 mcg/kg dexmedetomidine compared to placebo. There was a significant increase in median sedation score at all time points postsedation compared to baseline (P < .018). Changes in MSC for the metatarsus were not significantly different between treatments at any time point (P = .12). For the flank, MSC was significantly higher for cats treated with dexmedetomidine compared to baseline (P ≤ .01). Skin perfusion to the flank decreased as early as 5 minutes posttreatment with dexmedetomidine and persisted for at least 15 minutes, regardless of dexmedetomidine dose.
CLINICAL RELEVANCE
Dexmedetomidine decreased skin perfusion in cats, even at low doses. Veterinarians may elect for an alternative sedative medication when decreased skin perfusion is a concern.
Topics: Cats; Animals; Dexmedetomidine; Hypnotics and Sedatives; Heart Rate; Perfusion
PubMed: 38039627
DOI: 10.2460/ajvr.23.06.0137 -
Transplantation Mar 2024Dynamic preservation methods such as normothermic, subnormothermic, and hypothermic machine perfusion circuits have emerged as viable alternatives to conventional static... (Review)
Review
Dynamic preservation methods such as normothermic, subnormothermic, and hypothermic machine perfusion circuits have emerged as viable alternatives to conventional static cold storage. These organ perfusion technologies serve as preservation methods and enable organ assessment, reconditioning, and repair before transplantation. Gene therapy is a novel strategy with the potential to transform the field of graft optimization and treatment. Thereby specific pathways involved in the transplantation process can be targeted and modified. This review aims to provide an overview of gene delivery methods during ex vivo machine perfusion of kidney and liver grafts. Recent literature on state-of-the-art gene therapy approaches during ex situ organ preservation, especially with respect to ischemia-reperfusion injury, as well as acute and chronic graft rejection have been analyzed. Additionally, potential challenges that could affect further refinement of this therapeutic modality are outlined.
Topics: Perfusion; Kidney; Organ Preservation; Kidney Transplantation; Extracorporeal Circulation
PubMed: 37482634
DOI: 10.1097/TP.0000000000004738 -
Fertility and Sterility Dec 2023To describe the feasibility of hypothermic machine perfusion (HMP) in uterus transplantation (UT) to potentially improve the preservation of the uterus and enhance graft...
OBJECTIVE
To describe the feasibility of hypothermic machine perfusion (HMP) in uterus transplantation (UT) to potentially improve the preservation of the uterus and enhance graft preservation in the donation after brainstem death (DBD) context. Uterus transplantation is a new surgical approach to treating absolute uterine infertility; it can be performed after living donation or after DBD. In the DBD context, the uterus is typically the last organ removed after other vital organs, with the exception of the Baylor team, which removes the uterus first. This key aspect imposes an unavoidable mild temperature ischemia for >1 hour on the uterus during the removal of the vital abdominal and chest organs. In renal transplantation, the perfusion machine reduces the risk of delayed graft function; thus, we hypothesized that machine perfusion could result in a reduction of uterus graft dysfunction. The uterus graft dysfunction could be expressed by a low embryo implantation rate, pregnancy loss, or vascular pregnancy diseases such as preeclampsia or fetal growth restriction." To date, static cold storage of the uterus is the only standard method for preservation before transplantation. HMP is an emerging method that could potentially improve the preservation of the uterus to enhance graft preservation in the DBD context.
DESIGN
This video article shows all the technical details of using the HMP for uterine transplantation.
SETTING
University.
ANIMALS
Porcine model.
INTERVENTION
Porcine uterus was retrieved from a DBD domestic animal model and flushed with KPS MP (Bridge To Life Ltd in UK) at 4 °C. After vascular preparation on the back table, the uterus was perfused using KPS MP through a cannula in the aorta using the VitaSmart device (Bridge To Life Ltd in UK) for 18 hours. Then, the uterus was transplanted to the porcine recipient.
MAIN OUTCOME MEASURES
The macroscopic appearance of the uterus at the end of HMP and the assessment of the uterus vascularization after transplantation in the recipient compared with the native uterus.
RESULTS
This video shows the cannulation of the iliac vessels, cooling and removal of the uterus on a porcine model, uterus preservation using HMP during 18 hours, and then UT in a new recipient pig with the reperfusion of the transplanted uterus next to the native, intact uterus of the recipient. The macroscopic appearance of the uterus at the end of HMP appeared viable and was perfectly flushed. The assessment of the uterus vascularization after transplantation in the recipient was similar to that of the native uterus. To our knowledge, we describe here for the first time the UT procedure in DBD context on an animal model and the use of HMP for uterus preservation in UT programs; this could increase the number of uterine grafts available for a greater number of female recipients.
CONCLUSION
Hypothermic machine perfusion could allow the duration of cold ischemia to be prolonged without altering the uterine graft. Nevertheless, this assertion has to be validated in a human context.
Topics: Animals; Female; Cold Temperature; Organ Preservation; Perfusion; Swine; Uterus
PubMed: 37660880
DOI: 10.1016/j.fertnstert.2023.08.020 -
Liver Transplantation : Official... Dec 2017The efficacy of cold in situ perfusion and static storage of the liver is a possible determinant of transplantation outcomes. The aim of this study was to determine... (Meta-Analysis)
Meta-Analysis Review
The efficacy of cold in situ perfusion and static storage of the liver is a possible determinant of transplantation outcomes. The aim of this study was to determine whether there is evidence to substantiate a preference for a particular perfusion route (aortic or dual) or perfusion/preservation solution in donation after brain death (DBD) liver transplantation. The Embase, MEDLINE, and Cochrane databases were used (1980-2017). Random effects modeling was used to estimate effects on transplantation outcomes based on (1) aortic or dual in situ perfusion and (2) the use of University of Wisconsin (UW), histidine tryptophan ketoglutarate (HTK), Celsior, and/or Institut Georges Lopez-1 (IGL-1) solutions for perfusion/preservation. A total of 22 articles were included (2294 liver transplants). The quality of evidence ranged from very low to moderate Grading of Recommendations, Assessment, Development and Evaluations score. Meta-analyses were conducted for 14 eligible studies. Although there was no difference in the primary nonfunction (PNF) rate, a higher peak alanine aminotransferase (ALT) was recorded in dual compared with aortic-only UW-perfused livers (standardized mean difference, 0.24; 95% confidence interval, 0.01-0.47); a back-table portal venous flush was undertaken in the majority of aortic-only perfused livers. There were no relevant differences in peak enzymes, PNF, thrombotic graft loss, biliary complications, or 1-year graft survival in comparisons between dual-perfused livers using UW, HTK, Celsior, or IGL-1. In conclusion, there is no significant evidence that aortic-only perfusion of the DBD liver compromises transplantation outcomes, and it may be favored because of its simplicity. However, there is currently insufficient evidence to advocate for the use of any particular perfusion/preservation fluid over the others. Liver Transplantation 23 1615-1627 2017 AASLD.
Topics: Allografts; Cold Ischemia; Graft Survival; Humans; Liver; Liver Transplantation; Organ Preservation; Organ Preservation Solutions; Perfusion; Practice Guidelines as Topic; Tissue and Organ Procurement; Treatment Outcome
PubMed: 28734125
DOI: 10.1002/lt.24829 -
Frontiers in Immunology 2022The frequent use of marginal livers forces transplant centres to explore novel technologies to improve organ quality and outcomes after implantation. Organ perfusion... (Review)
Review
The frequent use of marginal livers forces transplant centres to explore novel technologies to improve organ quality and outcomes after implantation. Organ perfusion techniques are therefore frequently discussed with an ever-increasing number of experimental and clinical studies. Two main approaches, hypothermic and normothermic perfusion, are the leading strategies to be introduced in clinical practice in many western countries today. Despite this success, the number of studies, which provide robust data on the underlying mechanisms of protection conveyed through this technology remains scarce, particularly in context of different stages of ischemia-reperfusion-injury (IRI). Prior to a successful clinical implementation of machine perfusion, the concept of IRI and potential key molecules, which should be addressed to reduce IRI-associated inflammation, requires a better exploration. During ischemia, Krebs cycle metabolites, including succinate play a crucial role with their direct impact on the production of reactive oxygen species (ROS) at mitochondrial complex I upon reperfusion. Such features are even more pronounced under normothermic conditions and lead to even higher levels of downstream inflammation. The direct consequence appears with an activation of the innate immune system. The number of articles, which focus on the impact of machine perfusion with and without the use of specific perfusate additives to modulate the inflammatory cascade after transplantation is very small. This review describes first, the subcellular processes found in mitochondria, which instigate the IRI cascade together with proinflammatory downstream effects and their link to the innate immune system. Next, the impact of currently established machine perfusion strategies is described with a focus on protective mechanisms known for the different perfusion approaches. Finally, the role of such dynamic preservation techniques to deliver specific agents, which appear currently of interest to modulate this posttransplant inflammation, is discussed together with future aspects in this field.
Topics: Humans; Immunity; Inflammation; Liver Transplantation; Organ Preservation; Perfusion
PubMed: 35874758
DOI: 10.3389/fimmu.2022.855263