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ACS Chemical Neuroscience Jul 2023Information about the rates of hydrolysis of neuropeptides by extracellular peptidases can lead to a quantitative understanding of how the steady-state and transient...
Information about the rates of hydrolysis of neuropeptides by extracellular peptidases can lead to a quantitative understanding of how the steady-state and transient concentrations of neuropeptides are controlled. We have created a small microfluidic device that electroosmotically infuses peptides into, through, and out of the tissue to a microdialysis probe outside the head. The device is created by two-photon polymerization (Nanoscribe). Inferring quantitative estimates of a rate process from the change in concentration of a substrate that has passed through tissue is challenging for two reasons. One is that diffusion is significant, so there is a distribution of peptide substrate residence times in the tissue. This affects the product yield. The other is that there are multiple paths taken by the substrate as it passes through tissue, so there is a distribution of residence times and thus reaction times. Simulation of the process is essential. The simulations presented here imply that a range of first order rate constants of more than 3 orders of magnitude is measurable and that 5-10 min is required to reach a steady state value of product concentration following initiation of substrate infusion. Experiments using a peptidase-resistant d-amino acid pentapeptide, yaGfl, agree with simulations.
Topics: Microdialysis; Peptides; Perfusion; Computer Simulation; Neuropeptides
PubMed: 37379416
DOI: 10.1021/acschemneuro.3c00057 -
Liver Transplantation : Official... Jan 2024In Italy, 20 minutes of continuous, flat-line electrocardiogram are required for death declaration, which significantly increases the risks of donation after circulatory...
In Italy, 20 minutes of continuous, flat-line electrocardiogram are required for death declaration, which significantly increases the risks of donation after circulatory death (DCD) LT. Despite prolonged warm ischemia time, Italian centers reported good outcomes in controlled donation after circulatory death LT by combining normothermic regional and end-ischemic machine perfusion. However, data on uncontrolled DCD (uDCD) LT performed by this approach are lacking. This was a multicenter, retrospective study performed at 3 large-volume centers comparing clinical outcomes of uncontrolled versus controlled DCD LT. The aim of the study was to assess outcomes of sequential normothermic regional perfusion and end-ischemic machine perfusion in uncontrolled DCD liver transplantation (LT). Of 153 DCD donors evaluated during the study period, 40 uDCD and 59 donation after circulatory death grafts were transplanted (utilization rate 52% vs. 78%, p = 0.004). Recipients of uDCD grafts had higher MEAF (4.9 vs. 3.5, p < 0.001) and CCI scores at discharge (24.4 vs. 8.7, p = 0.026), longer ICU stay (5 vs. 4 d, p = 0.047), and a trend toward more severe AKI. At multivariate analysis, 90-day graft loss was associated with recipient BMI and lactate downtrend during normothermic regional perfusion. One-year graft survival was lower in uDCD (75% vs. 90%, p = 0.007) but became comparable when non-liver-related graft losses were treated as censors (77% vs. 90%, p = 0.100). The incidence of ischemic cholangiopathy was 10% in uDCD versus 3% in donation after circulatory death, p = 0.356. uDCD LT with prolonged warm ischemia is feasible by the sequential use of normothermic regional perfusion and end-ischemic machine perfusion. Proper donor and recipient selection are key to achieving good outcomes in this setting.
Topics: Humans; Liver Transplantation; Retrospective Studies; Perfusion; Tissue Donors; Graft Survival; Lactic Acid; Tissue and Organ Procurement; Organ Preservation
PubMed: 37450659
DOI: 10.1097/LVT.0000000000000219 -
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 -
Heart, Lung & Circulation Mar 2024
Topics: Humans; Hyperemia; Heart Failure; Kidney; Perfusion
PubMed: 38580419
DOI: 10.1016/j.hlc.2024.03.001 -
American Journal of Transplantation :... Jan 2024Heart transplantation using donation after circulatory death (DCD) was recently adopted in the United States. This study aimed to characterize organ yield from adult...
Heart transplantation using donation after circulatory death (DCD) was recently adopted in the United States. This study aimed to characterize organ yield from adult (≥18 years) DCD heart donors in the United States using the United Network for Organ Sharing registry. The registry does not identify potential donors who do not progress to circulatory death, and only those who progressed to death were included for analysis. Outcomes included organ recovery from the donor operating room and organ utilization for transplant. Multiple logistic regression was used to identify predictors of heart recovery and utilization. Among 558 DCD procurements, recovery occurred in 89.6%, and 92.5% of recovered hearts were utilized for transplant. Of 506 DCD procurements with available data, 65.0% were classified as direct procurement and perfusion and 35.0% were classified as normothermic regional perfusion (NRP). Logistic regression identified that NRP, shorter agonal time, younger donor age, and highest volume of organ procurement organizations were independently associated with increased odds for heart recovery. NRP independently predicted heart utilization after recovery. DCD heart utilization in the United States is satisfactory and consistent with international experience. NRP procurements have a higher yield for DCD heart transplantation compared with direct procurement and perfusion, which may reflect differences in donor assessment and acceptance criteria.
Topics: Adult; Humans; United States; Tissue Donors; Heart Transplantation; Tissue and Organ Procurement; Perfusion; Heart; Death; Organ Preservation
PubMed: 37517554
DOI: 10.1016/j.ajt.2023.07.019 -
Frontiers in Immunology 2024Primary graft dysfunction (PGD) is a common complication after lung transplantation. A plethora of contributing factors are known and assessment of donor lung function... (Review)
Review
Primary graft dysfunction (PGD) is a common complication after lung transplantation. A plethora of contributing factors are known and assessment of donor lung function prior to organ retrieval is mandatory for determination of lung quality. Specialized centers increasingly perform ex vivo lung perfusion (EVLP) to further assess lung functionality and improve and extend lung preservation with the aim to increase lung utilization. EVLP can be performed following different protocols. The impact of the individual EVLP parameters on PGD development, organ function and postoperative outcome remains to be fully investigated. The variables relate to the engineering and function of the respective perfusion devices, such as the type of pump used, functional, like ventilation modes or physiological (e.g. perfusion solutions). This review reflects on the individual technical and fluid components relevant to EVLP and their respective impact on inflammatory response and outcome. We discuss key components of EVLP protocols and options for further improvement of EVLP in regard to PGD. This review offers an overview of available options for centers establishing an EVLP program and for researchers looking for ways to adapt existing protocols.
Topics: Humans; Lung Injury; Lung; Perfusion; Lung Transplantation; Tissue Donors
PubMed: 38510260
DOI: 10.3389/fimmu.2024.1358153 -
Perfusion Nov 2023To explore impact of various periods of ischemia and reperfusion on the severity of myocardial injury.
BACKGROUND
To explore impact of various periods of ischemia and reperfusion on the severity of myocardial injury.
METHODS
Langendorff model of isolated cardiac perfusion system was established in 56 rat hearts. They were randomly assigned into four groups with four different ischemia (perfusion-pause) time and reperfusion time. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and creatine kinase-MB (CK-MB) were measured and the size of myocardial infarction was assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining.
RESULTS
The levels of AST, ALT, LDH, and CK-MB in the heart tissues and perfusate were lowest in the group I (shortest time of perfusion-pause and reperfusion) followed by the groups II, III, and IV (longest time of perfusion-pause and reperfusion) ( < 0.05). The myocardial infarction size was smallest in the group I (6.63 ± 0.47) followed by group II (15.12 ± 1.03), group III (20.32 ± 2.18), and group IV (32.29 ± 5.42) ( < 0.05). Two-way ANOVA analysis revealed that period of perfusion-pause and reperfusion independently and significantly affected the levels of AST and ALT in both heart tissues and perfusate ( < 0.001). The interaction of pausing period and reperfusion significantly affected the level of AST ( = 0.046) and CK-MB ( = 0.001) in the perfusate. In addition, perfusion-pause period significantly affected levels of LDH and CK-MB only in the perfusate ( < 0.001). Neither perfusate nor heart tissue LDH level was significantly affected by the interaction of perfusion-pause and reperfusion period ( > 0.05).
CONCLUSION
The severity of myocardial injury in the Langendorff model was affected by the period of perfusion-pause and reperfusion. The longer period of perfusion-pause followed by the longer the period of reperfusion, the severe myocardial injury was found.
Topics: Rats; Animals; Myocardial Reperfusion Injury; Heart; Myocardial Infarction; Heart Injuries; Reperfusion; Perfusion; L-Lactate Dehydrogenase
PubMed: 36059244
DOI: 10.1177/02676591221122349 -
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 Heart and Lung... Sep 2023Use of thoracoabdominal normothermic regional perfusion (TA-NRP) during donation after circulatory death (DCD) is an important advance in organ donation. Prior to...
Use of thoracoabdominal normothermic regional perfusion (TA-NRP) during donation after circulatory death (DCD) is an important advance in organ donation. Prior to establishing TA-NRP, the brachiocephalic, left carotid, and left subclavian arteries are ligated, thereby eliminating anterograde brain blood flow via the carotid and vertebral arteries. While theoretical concerns have been voiced that TA-NRP after DCD may restore brain blood flow via collaterals, there have been no studies to confirm or refute this possibility. We evaluated brain blood flow using intraoperative transcranial Doppler (TCD) in two DCD TA-NRP cases. Pre-extubation, anterior and posterior circulation brain blood flow waveforms were present in both cases, similar to the waveforms detected in a control patient on mechanical circulatory support undergoing cardiothoracic surgery. Following declaration of death and initiation of TA-NRP, no brain blood flow was detected in either case. Additionally, there was absence of brainstem reflexes, no response to noxious stimuli and no respiratory effort. These TCD results demonstrate that DCD with TA-NRP did not restore brain blood flow.
Topics: Humans; Tissue Donors; Organ Preservation; Perfusion; Tissue and Organ Procurement; Organ Transplantation; Death; Graft Survival
PubMed: 37211334
DOI: 10.1016/j.healun.2023.05.010 -
Perfusion Oct 2023The landmark 2016 Minimal Invasive Extracorporeal Technologies International Society (MiECTiS) position paper promoted the creation of a common language between cardiac... (Review)
Review
The landmark 2016 Minimal Invasive Extracorporeal Technologies International Society (MiECTiS) position paper promoted the creation of a common language between cardiac surgeons, anesthesiologists and perfusionists which led to the development of a stable framework that paved the way for the advancement of minimal invasive perfusion and related technologies. The current expert consensus document offers an update in areas for which new evidence has emerged. In the light of published literature, modular minimal invasive extracorporeal circulation (MiECC) has been established as a safe and effective perfusion technique that increases biocompatibility and ultimately ensures perfusion safety in all adult cardiac surgical procedures, including re-operations, aortic arch and emergency surgery. Moreover, it was recognized that incorporation of MiECC strategies advances minimal invasive cardiac surgery (MICS) by combining reduced surgical trauma with minimal physiologic derangements. Minimal Invasive Extracorporeal Technologies International Society considers MiECC as a physiologically-based multidisciplinary strategy for performing cardiac surgery that is associated with significant evidence-based clinical benefit that has accrued over the years. Widespread adoption of this technology is thus strongly advocated to obtain additional healthcare benefit while advancing patient care.
Topics: Adult; Humans; Cardiac Surgical Procedures; Extracorporeal Circulation; Perfusion; Minimally Invasive Surgical Procedures; Heart
PubMed: 35961654
DOI: 10.1177/02676591221119002