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Transplantation Aug 2022Ischemia-reperfusion injury remains a primary concern in upper extremity transplantation. Ex vivo normothermic perfusion (EVNP) enables near-physiological organ...
BACKGROUND
Ischemia-reperfusion injury remains a primary concern in upper extremity transplantation. Ex vivo normothermic perfusion (EVNP) enables near-physiological organ preservation, avoiding the deleterious effects of hypoxia and cooling. We investigated the effectiveness of human limb EVNP compared with static cold storage (SCS).
METHODS
Twenty human upper extremities were procured. Ten were perfused at 38 °C with an oxygenated red blood cell-based solution, and contralateral limbs served as SCS control (4 °C). EVNP was terminated with systolic arterial pressure ≥115 mm Hg, compartment fullness, or a 20% decline in oxygen saturation. Weight, contractility, compartment pressure, tissue oxygen saturation, and uptake rates were assessed. Perfusate fluid dynamics, gases, electrolytes, and metabolites were measured. Myocyte injury scores and liquid chromatography-mass spectrometry analysis were performed.
RESULTS
EVNP duration was 41.6 ± 9.4 h. Vascular resistance averaged 173.0 ± 29.4 mm Hg × min/L. Weight change and compartment pressures were 0.4 ± 12.2% ( P = 0.21) and 21.7 ± 15.58 mm Hg ( P = 0.003), respectively. Arterial and venous carbon dioxide partial pressure, oxygen saturation, and pH were 509.5 ± 91.4 mm Hg, 15.7 ± 30.2 mm Hg, 87.4 ± 11.4%, and 7.3 ± 0.2, respectively. Oxygen uptake rates averaged 5.7 ± 2.8 mL/min/g. Lactate reached 20 mmol/L after 15 (interquartile range = 6) h. Limb contractility was preserved for 30.5 (interquartile range = 15.8) h ( P < 0.001) and negatively correlated with perfusate potassium (ρ = -0.7, P < 0.001). Endpoint myocyte injury scores were 28.9 ± 11.5% (EVNP) and 90.2 ± 11.8% (SCS) ( P < 0.001). A significant increase in taurine ( P = 0.002) and decrease in tryptophan ( P = 0.002) were detected. Infrared thermography and indocyanine green angiography confirmed the presence of peripheral perfusion.
CONCLUSIONS
EVNP can overcome the limitations of cold preservation by extending preservation times, enabling limb quality assessment, and allowing limb reconditioning before transplantation.
Topics: Extracorporeal Circulation; Humans; Organ Preservation; Organ Preservation Solutions; Perfusion; Upper Extremity
PubMed: 35152257
DOI: 10.1097/TP.0000000000004045 -
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 -
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 -
Chirurgie (Heidelberg, Germany) Oct 2022Insufficiency of gastrointestinal anastomoses represents a relevant risk of morbidity and mortality for affected patients. The perfusion quality of the ends of the... (Review)
Review
Insufficiency of gastrointestinal anastomoses represents a relevant risk of morbidity and mortality for affected patients. The perfusion quality of the ends of the intestine is the decisive parameter for ensuring sufficient healing of an anastomosis. Intraoperative fluorescence-guided perfusion assessment with indocyanine green is increasingly being used in modern visceral surgery to evaluate tissue perfusion prior to the fashioning of gastrointestinal anastomoses. This technique provides the possibility to distinguish between adequately and inadequately perfused tissue in order to place the anastomosis in the region with the best possible perfusion. Thus, surgeons have a measuring instrument that enables an objective assessment of the perfusion quality of the tissue to be undertaken in addition to a purely subjective macroscopic visual assessment, in order to achieve a better functional result for the patients. Currently, however, the value of this technique has not yet been conclusively clarified. The aim of this review article is to characterize the benefits of intraoperative fluorescence-guided perfusion assessment and to classify it with respect to its significance for routine clinical practice.
Topics: Anastomosis, Surgical; Anastomotic Leak; Fluorescein Angiography; Humans; Indocyanine Green; Perfusion
PubMed: 35804154
DOI: 10.1007/s00104-022-01679-8 -
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 -
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 -
Expert Review of Medical Devices Mar 2018The number of organs available for heart and lung transplantation is far short of the number that is needed to meet demand. Perfusion and ventilation of donor organs...
INTRODUCTION
The number of organs available for heart and lung transplantation is far short of the number that is needed to meet demand. Perfusion and ventilation of donor organs after procurement has led to exciting advances in the field of cardiothoracic transplantation. The clinical implications of this technology allows for techniques to evaluate the quality of an organ, active rehabilitation of organs after procurement and prior to implantation, and increased time between organ procurement and implantation. This ex-vivo perfusion technique has also been referred to in the lay press as the 'heart in a box' or 'lung in a box.'
AREAS COVERED
This review includes information from case reports, case series, and clinical trials on ex vivo heart and lung perfusion. The focus is on the devices, ventilation and perfusion techniques, outcomes, and application of the technology.
EXPERT COMMENTARY
Ex vivo perfusion of donor hearts and lungs prior to transplantation has proven to be a viable alternative to standard cold-preservation strategies. Its use has allowed for ongoing expansion of the donor pool. The biggest barriers to expansion of this technology are access, cost, and lack of evidence which clearly supports superior outcomes.
Topics: Animals; Heart; Heart Transplantation; Humans; Lung; Lung Transplantation; Perfusion
PubMed: 29376452
DOI: 10.1080/17434440.2018.1430568 -
Artificial Organs Nov 2023Lung transplantation is accepted as a well-established and effective treatment for patients with end-stage lung disease. While the number of candidates added to the... (Review)
Review
Lung transplantation is accepted as a well-established and effective treatment for patients with end-stage lung disease. While the number of candidates added to the waitlist continues to rise, the number of transplants performed remains limited by the number of suitable organ donors. Ex vivo lung perfusion (EVLP) emerged as a method of addressing the organ shortage by allowing the evaluation and potential reconditioning of marginal donor lungs or minimizing risks of prolonged ischemic time due to logistical challenges. The currently available FDA-approved EVLP systems have demonstrated excellent outcomes in clinical trials, and retrospective studies have demonstrated similar post-transplant survival between recipients who received marginal donor lungs perfused using EVLP and recipients who received standard criteria lungs stored using conventional methods. Despite this, widespread utilization has plateaued in the last few years, likely due to the significant costs associated with initiating EVLP programs. Centralized, dedicated EVLP perfusion centers are currently being investigated as a potential method of further expanding utilization of this technology. In the preclinical setting, potential applications of EVLP that are currently being studied include prolongation of organ preservation, reconditioning of unsuitable lungs, and further enhancement of already suitable lungs. As adoption of EVLP technology becomes more widespread, we may begin to see future implementation of these potential applications into the clinical setting.
Topics: Humans; Perfusion; Retrospective Studies; Lung; Extracorporeal Circulation; Lung Transplantation; Organ Preservation
PubMed: 37455548
DOI: 10.1111/aor.14607 -
ASAIO Journal (American Society For... Jul 2023Ex vivo lung perfusion (EVLP) is a method of organ preservation to expand the donor pool by allowing organ assessment and repair. Perfusion solution composition is...
Ex vivo lung perfusion (EVLP) is a method of organ preservation to expand the donor pool by allowing organ assessment and repair. Perfusion solution composition is crucial to maintaining and improving organ function during EVLP. EVLP compared perfusates supplemented with either polymeric human serum albumin (PolyHSA) or standard human serum albumin (HSA). Rat heart-lung blocks underwent normothermic EVLP (37°C) for 120 minutes using perfusate with 4% HSA or 4% PolyHSA synthesized at a 50:1 or 60:1 molar ratio of glutaraldehyde to PolyHSA. Oxygen delivery, lung compliance, pulmonary vascular resistance (PVR), wet-to-dry ratio, and lung weight were measured. Perfusion solution type (HSA or PolyHSA) significantly impacted end-organ metrics. Oxygen delivery, lung compliance, and PVR were comparable among groups ( P > 0.05). Wet-to-dry ratio increased in the HSA group compared to the PolyHSA groups (both P < 0.05) suggesting edema formation. Wet-to-dry ratio was most favorable in the 60:1 PolyHSA-treated lungs compared to HSA ( P < 0.05). Compared to using HSA, PolyHSA significantly lessened lung edema. Our data confirm that the physical properties of perfusate plasma substitutes significantly impact oncotic pressure and the development of tissue injury and edema. Our findings demonstrate the importance of perfusion solutions and PolyHSA is an excellent candidate macromolecule to limit pulmonary edema. http://links.lww.com/ASAIO/A980.
Topics: Humans; Animals; Rats; Lung Transplantation; Lung; Perfusion; Serum Albumin, Human; Organ Preservation; Oxygen
PubMed: 36976617
DOI: 10.1097/MAT.0000000000001918