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International Journal of Molecular... Jul 2023The impact of the machine perfusion of donation after circulatory death (DCD) hearts with the novel Custodiol-N solution on diastolic and coronary microvascular...
The impact of the machine perfusion of donation after circulatory death (DCD) hearts with the novel Custodiol-N solution on diastolic and coronary microvascular dysfunction is unknown. Porcine DCD-hearts were maintained four hours by perfusion with normothermic blood (DCD-B), hypothermic Custodiol (DCD-C), or Custodiol-N (DCD-CN), followed by one hour of reperfusion with fresh blood, including microvascular and contractile evaluation. In another group (DCD group), one hour of reperfusion, including microvascular and contractile evaluation, was performed without a previous maintenance period (all groups N = 5). We measured diastolic function with a balloon catheter and microvascular perfusion by Laser-Doppler-Technology, resulting in Laser-Doppler-Perfusion (LDP). We performed immunohistochemical staining and gene expression analysis. The developed pressure was improved in DCD-C and DCD-CN. The diastolic pressure decrement (DCD-C: -1093 ± 97 mmHg/s; DCD-CN: -1703 ± 329 mmHg/s; DCD-B: -690 ± 97 mmHg/s; < 0.05) and relative LDP (DCD-CN: 1.42 ± 0.12; DCD-C: 1.11 ± 0.13; DCD-B: 1.22 ± 0.27) were improved only in DCD-CN. In DCD-CN, the expression of eNOS increased, and ICAM and VCAM decreased. Only in DCD-B compared to DCD, the pathways involved in complement and coagulation cascades, focal adhesion, fluid shear stress, and the IL-6 and IL-17 pathways were upregulated. In conclusion, machine perfusion with Custodiol-N improves diastolic and microvascular function and preserves the microvascular endothelium of porcine DCD-hearts.
Topics: Swine; Animals; Heart Transplantation; Heart; Reperfusion; Perfusion; Tissue Donors; Organ Preservation; Death
PubMed: 37511318
DOI: 10.3390/ijms241411562 -
International Journal of Molecular... Nov 2023Heart transplantation remains the conventional treatment in end-stage heart failure, with static cold storage (SCS) being the standard technique used for donor... (Review)
Review
Heart transplantation remains the conventional treatment in end-stage heart failure, with static cold storage (SCS) being the standard technique used for donor preservation. Nevertheless, prolonged cold ischemic storage is associated with the increased risk of early graft dysfunction attributed to residual ischemia, reperfusion, and rewarming damage. In addition, the demand for the use of marginal grafts requires the development of new methods for organ preservation and repair. In this review, we focus on current knowledge and novel methods of donor preservation in heart transplantation. Hypothermic or normothermic machine perfusion may be a promising novel method of donor preservation based on the administration of cardioprotective agents. Machine perfusion seems to be comparable to cold cardioplegia regarding donor preservation and allows potential repair treatments to be employed and the assessment of graft function before implantation. It is also a promising platform for using marginal organs and increasing donor pool. New pharmacological cardiac repair treatments, as well as cardioprotective interventions have emerged and could allow for the optimization of this modality, making it more practical and cost-effective for the real world of transplantation. Recently, the use of triiodothyronine during normothermic perfusion has shown a favorable profile on cardiac function and microvascular dysfunction, likely by suppressing pro-apoptotic signaling and increasing the expression of cardioprotective molecules.
Topics: Humans; Tissue Donors; Heart Transplantation; Organ Preservation; Perfusion; Ischemia
PubMed: 38069017
DOI: 10.3390/ijms242316693 -
Annals of Surgery Nov 2023To develop a protocol for the defatting of steatotic liver grafts during long-term ex situ normothermic machine perfusion.
OBJECTIVE
To develop a protocol for the defatting of steatotic liver grafts during long-term ex situ normothermic machine perfusion.
BACKGROUND
Despite the alarming increase in donor organ shortage, the highly prevalent fatty liver grafts are often discarded due to the risk of primary nonfunction. Effective strategies preventing such outcomes are currently lacking. An exciting new avenue is the introduction of ex situ normothermic machine perfusion (NMP), enabling a liver to remain fully functional for up to 2 weeks and providing a unique window of opportunity for defatting before transplantation.
METHODS
Over a 5-year period, 23 discarded liver grafts and 28 partial livers from our resection program were tested during ex situ normothermic machine perfusion. The steatosis degree was determined on serial biopsies by expert pathologists, and triglyceride contents were measured simultaneously.
RESULTS
Of 51 liver grafts, 20 were steatotic, with up to 85% macrovesicular steatosis, and were perfused for up to 12 days. Ten livers displayed marked (5 of which almost complete) loss of fat, while the other 10 did not respond to long-term perfusion. Successful defatting was related to prolonged perfusion, automated glucose control, circadian nutrition, and L-carnitine/fenofibrate supplementation. Pseudopeliotic steatosis and the associated activation of Kupffer/stellate cells were unexpected processes that might contribute to defatting. Synthetic and metabolic functions remained preserved for most grafts until perfusion ended.
CONCLUSION
Ex situ long-term perfusion effectively reduces steatosis while preserving organ viability and may in the future allow transplantation of primarily unusable high-risk grafts, significantly increasing the number of organs available for transplantation.
Topics: Humans; Organ Preservation; Liver; Fatty Liver; Liver Transplantation; Perfusion
PubMed: 37497663
DOI: 10.1097/SLA.0000000000006047 -
Advanced Healthcare Materials Aug 2023Extracellular vesicles (EVs) are implicated as promising therapeutics and drug delivery vehicles in various diseases. However, successful clinical translation will...
Extracellular vesicles (EVs) are implicated as promising therapeutics and drug delivery vehicles in various diseases. However, successful clinical translation will depend on the development of scalable biomanufacturing approaches, especially due to the documented low levels of intrinsic EV-associated cargo that may necessitate repeated doses to achieve clinical benefit in certain applications. Thus, here the effects of a 3D-printed scaffold-perfusion bioreactor system are assessed on the production and bioactivity of EVs secreted from bone marrow-derived mesenchymal stem cells (MSCs), a cell type widely implicated in generating EVs with therapeutic potential. The results indicate that perfusion bioreactor culture induces an ≈40-80-fold increase (depending on measurement method) in MSC EV production compared to conventional cell culture. Additionally, MSC EVs generated using the perfusion bioreactor system significantly improve wound healing in a diabetic mouse model, with increased CD31 staining in wound bed tissue compared to animals treated with flask cell culture-generated MSC EVs. Overall, this study establishes a promising solution to a major EV translational bottleneck, with the capacity for tunability for specific applications and general improvement alongside advancements in 3D-printing technologies.
Topics: Animals; Mice; Extracellular Vesicles; Bioreactors; Perfusion; Mesenchymal Stem Cells; Printing, Three-Dimensional
PubMed: 36930747
DOI: 10.1002/adhm.202300584 -
Brazilian Journal of Cardiovascular... Oct 2023
Topics: Humans; Perfusion; Surveys and Questionnaires; Delivery of Health Care
PubMed: 37797244
DOI: 10.21470/1678-9741-2022-0474 -
Transplantation Feb 2024On June 3, 2023, the American Society of Transplant Surgeons convened a meeting in San Diego, California to (1) develop a consensus statement with supporting data on the...
On June 3, 2023, the American Society of Transplant Surgeons convened a meeting in San Diego, California to (1) develop a consensus statement with supporting data on the ethical tenets of thoracoabdominal normothermic regional perfusion (NRP) and abdominal NRP; (2) provide guidelines for the standards of practice that should govern thoracoabdominal NRP and abdominal NRP; and (3) develop and implement a central database for the collection of NRP donor and recipient data in the United States. National and international leaders in the fields of neuroscience, transplantation, critical care, NRP, Organ Procurement Organizations, transplant centers, and donor families participated. The conference was designed to focus on the controversial issues of neurological flow and function in donation after circulatory death donors during NRP and propose technical standards necessary to ensure that this procedure is performed safely and effectively. This article discusses major topics and conclusions addressed at the meeting.
Topics: Humans; Perfusion; Tissue Donors; Consensus; Critical Care; Surgeons
PubMed: 38254280
DOI: 10.1097/TP.0000000000004894 -
Biologicals : Journal of the... Nov 2023In the current transition to intensified upstream processing, the risks of adopting traditional single-use systems for high-titer, long-duration perfusion cultures, have...
In the current transition to intensified upstream processing, the risks of adopting traditional single-use systems for high-titer, long-duration perfusion cultures, have thus far not been considered. This case study uses the Failure Modes and Effects Analysis (FMEA) method to evaluate the risks associated with implementing upstream single-use technology. The simulated model process was used to compare the risk level of single-use technology for a traditional fed-batch cell culture with that for perfusion culture, under the same annual protein production conditions. To provide a reasonable source of potential risk for FMEA, all single-use upstream operations for both fed-batch and perfusion processes were investigated using an analytical method developed to quantify the impact of process parameters and operating conditions on single-use system specifications and to ensure objectivity. Many of the risks and their levels, were similar in long-duration perfusion cultures and fed-batch cultures. However, differences were observed for high-risk components such as daily sampling and installation. The result of this analysis indicates that the reasons for risk are different for fed-batch cultures and perfusion cultures such as larger bioreactors in fed-batch and longer runs in perfusion, respectively. This risk assessment method could identify additional control measures and be part of a holistic contamination control strategy and help visualize their effectiveness.
Topics: Animals; Cricetinae; Biological Products; Bioreactors; Batch Cell Culture Techniques; Antibodies, Monoclonal; Perfusion; Cricetulus
PubMed: 37793309
DOI: 10.1016/j.biologicals.2023.101713 -
Tomography (Ann Arbor, Mich.) Nov 2023The number of scholarly articles continues to rise. The continuous increase in scientific output poses a challenge for researchers, who must devote considerable time to... (Review)
Review
The number of scholarly articles continues to rise. The continuous increase in scientific output poses a challenge for researchers, who must devote considerable time to collecting and analyzing these results. The topic modeling approach emerges as a novel response to this need. Considering the swift advancements in computed tomography perfusion (CTP), we deem it essential to launch an initiative focused on topic modeling. We conducted a comprehensive search of the Scopus database from 1 January 2000 to 16 August 2023, to identify relevant articles about CTP. Using the BERTopic model, we derived a group of topics along with their respective representative articles. For the 2020s, linear regression models were used to identify and interpret trending topics. From the most to the least prevalent, the topics that were identified include "Tumor Vascularity", "Stroke Assessment", "Myocardial Perfusion", "Intracerebral Hemorrhage", "Imaging Optimization", "Reperfusion Therapy", "Postprocessing", "Carotid Artery Disease", "Seizures", "Hemorrhagic Transformation", "Artificial Intelligence", and "Moyamoya Disease". The model provided insights into the trends of the current decade, highlighting "Postprocessing" and "Artificial Intelligence" as the most trending topics.
Topics: Humans; Tomography, X-Ray Computed; Stroke; Magnetic Resonance Imaging; Perfusion
PubMed: 37987344
DOI: 10.3390/tomography9060158 -
Ultraschall in Der Medizin (Stuttgart,... Aug 2023Microvascular blood flow (MBF) and its intramuscular regulation are of importance for physiological responsiveness and adaptation. The quantifiable in-vivo monitoring of...
PURPOSE
Microvascular blood flow (MBF) and its intramuscular regulation are of importance for physiological responsiveness and adaptation. The quantifiable in-vivo monitoring of MBF after cycling or systemic cold-water exposure may reveal new insights into capillary regulatory mechanisms. This study aimed to assess the role of exercise and cold therapy on MBF by using contrast-enhanced ultrasound (CEUS).
METHODS
Twenty healthy athletes were recruited and randomly assigned to an intervention (IG) or a control group (CG). MBF was quantified in superficial (rectus femoris, RF) and deep muscle layers (vastus intermedius, VI). Representative perfusion parameters (peak enhancement (PE) and wash-in area under the curve (WiAUC)) were measured after a standardized measurement protocol for both groups at resting conditions (t) and after cycling (20 min., 70% Watt max, t) for both groups, after cold-water immersion exposure for IG (15 min., 12°C) or after precisely 15 minutes of rest for CG (t) and for both groups after 60 minutes of follow-up (t).
RESULTS
At t, MBF in VI increased significantly compared to resting conditions in both groups in VI (p= 0.02). After the cold-water exposure (t), there were no statistically significant changes in perfusion parameters as well as after 60 minutes of follow-up (t) (p = 0.14).
CONCLUSION
Cycling leads to an upregulation of MBF. However, cold exposure does not change the MBF. The implementation of CEUS during different physiological demands may provide deeper insight into intramuscular perfusion regulation and regenerative processes.
Topics: Humans; Water; Muscles; Ultrasonography; Perfusion
PubMed: 37552977
DOI: 10.1055/a-2080-2937 -
Proceedings of the National Academy of... Mar 2024We present a comprehensive study on the non-invasive measurement of hippocampal perfusion. Using high-resolution 7 tesla arterial spin labeling (ASL) data, we generated...
We present a comprehensive study on the non-invasive measurement of hippocampal perfusion. Using high-resolution 7 tesla arterial spin labeling (ASL) data, we generated robust perfusion maps and observed significant variations in perfusion among hippocampal subfields, with CA1 exhibiting the lowest perfusion levels. Notably, these perfusion differences were robust and already detectable with 50 perfusion-weighted images per subject, acquired in 5 min. To understand the underlying factors, we examined the influence of image quality metrics, various tissue microstructure and morphometric properties, macrovasculature, and cytoarchitecture. We observed higher perfusion in regions located closer to arteries, demonstrating the influence of vascular proximity on hippocampal perfusion. Moreover, ex vivo cytoarchitectonic features based on neuronal density differences appeared to correlate stronger with hippocampal perfusion than morphometric measures like gray matter thickness. These findings emphasize the interplay between microvasculature, macrovasculature, and metabolic demand in shaping hippocampal perfusion. Our study expands the current understanding of hippocampal physiology and its relevance to neurological disorders. By providing in vivo evidence of perfusion differences between hippocampal subfields, our findings have implications for diagnosis and potential therapeutic interventions. In conclusion, our study provides a valuable resource for extensively characterizing hippocampal perfusion.
Topics: Perfusion; Arteries; Benchmarking; Hippocampus; Magnetic Resonance Imaging
PubMed: 38446857
DOI: 10.1073/pnas.2310044121