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The British Journal of Surgery May 2021Attempts to improve limb preservation for transplantation using ex vivo perfusion have yielded promising results. However, metabolic acidosis, aberrant perfusate...
BACKGROUND
Attempts to improve limb preservation for transplantation using ex vivo perfusion have yielded promising results. However, metabolic acidosis, aberrant perfusate biochemistry and significant perfusion-induced oedema are reported universally. Optimizing perfusion protocols is therefore essential for maintaining tissue health.
METHODS
A randomized, two-stage open preclinical trial design was used to determine the optimal temperature and mean arterial pressure for machine perfusion. Conditions compared were: normothermic machine perfusion at 70 mmHg (NMP-70); subnormothermic perfusion (28°C) at 70 mmHg; subnormothermic (28°C) perfusion at 50 mmHg; and hypothermic perfusion (10°C) at 30 mmHg. Following this, a head-to-head experiment was undertaken comparing the optimal machine perfusion with static cold storage. Paired bilateral limbs (10 in total) were randomized to either 8 h of static cold storage, or 2 h of static cold storage and 6 h of optimal machine perfusion. Both groups of limbs were then reperfused on a circuit primed with matched blood from unrelated donors for 4 h without immunosuppression.
RESULTS
NMP-70 resulted in less tissue injury and stable perfusion biochemistry. Assessing reperfusion outcomes, static cold storage resulted in acidosis with increased lactate and a worsening electrolyte profile, necessitating bolus infusions of bicarbonate to prevent graft loss. Conversely, NMP-70 was associated with haemodynamic and biochemical stability. Histologically, on reperfusion with allogeneic whole blood, limbs subjected to static cold storage exhibited multifocal ischaemic injury and increased inflammation, which was absent with NMP-70. Static cold storage also resulted in significant oedema compared with NMP-70.
CONCLUSION
Normothermic perfusion resulted in superior graft preservation and less reperfusion injury compared with the current static cold storage protocol.
Topics: Animals; Blood Pressure; Composite Tissue Allografts; Graft Survival; Models, Animal; Perfusion; Random Allocation; Reperfusion Injury; Specimen Handling; Swine; Temperature
PubMed: 34043778
DOI: 10.1002/bjs.11921 -
American Journal of Transplantation :... May 2022Pancreas transplantation improves and extends the life of patients with insulin-dependent diabetes. Pancreata from extended criteria donors have been increasingly used...
Pancreas transplantation improves and extends the life of patients with insulin-dependent diabetes. Pancreata from extended criteria donors have been increasingly used due to the scarcity of available grafts. Normothermic ex situ pancreas perfusion (NESPP) can keep grafts metabolically active, potentially allowing for assessment and organ repair, and could improve outcomes of marginal grafts. A novel NESPP technique was developed and tested. Porcine pancreata were removed after a short period of warm ischemia and subjected to 6 h of NESPP. Perfusion parameters, potential graft assessment markers and graft injury were measured. Next, pancreata subjected to 3 h of NESPP were transplanted and animals were followed for up to 3 days. Graft function and injury post-transplantation were evaluated. Using this novel system of perfusion, pancreata were perfused for an extended period of time with minimal edema. Histology at the end of perfusion showed intact islet cells with only mild signs of tissue injury. NESPP transplanted grafts showed immediate function after transplantation, with glucose levels in normal range. NESPP maintains a physiologic environment and excellent graft function without causing significant graft injury. Porcine pancreas transplantation is feasible and allows for in vivo graft assessment of pancreas function and injury after NESPP.
Topics: Animals; Humans; Organ Preservation; Pancreas; Pancreas Transplantation; Perfusion; Swine; Warm Ischemia
PubMed: 35258859
DOI: 10.1111/ajt.17019 -
The Journal of Extra-corporeal... Mar 2021
Topics: Humans; Perfusion
PubMed: 33814601
DOI: 10.1182/ject-531fte -
American Journal of Transplantation :... Apr 2020
Topics: Organ Preservation; Perfusion; Technology
PubMed: 32222099
DOI: 10.1111/ajt.15839 -
Muscle & Nerve Dec 2021For cubital tunnel syndrome, the avoidance of predisposing arm positions and the use of elbow splints are common conservative treatment options. The rationale is to...
INTRODUCTION/AIMS
For cubital tunnel syndrome, the avoidance of predisposing arm positions and the use of elbow splints are common conservative treatment options. The rationale is to prevent excessive stretching and compression of the nerve in the cubital tunnel, as this mechanical stress impedes intraneural perfusion. Data regarding those upper extremity postures to avoid, or whether elbow flexion alone is detrimental, are inconsistent. This study aimed to assess perfusion and size changes of the cubital tunnel during different postures in an experimental cadaver setup.
METHODS
Axillary arteries in 30 upper extremities of fresh cadavers were injected with ultrasound contrast agent. High-resolution ultrasound of the cubital tunnel was performed during five different arm postures that gradually increased tension on the ulnar nerve and caused cubital tunnel narrowing. Contrast enhancement within the tunnel was measured to quantify perfusion. Cubital tunnel cross-sectional area was measured to detect compression.
RESULTS
Increasing tension significantly reduced perfusion. When isolated, neither shoulder elevation, elbow flexion, pronation, nor extension of wrist and fingers impaired perfusion. However, combining two or more of these postures led to significant decreases. Significant narrowing of the cubital tunnel was seen in full elbow flexion and shoulder elevation.
DISCUSSION
Combinations of some upper extremity joint positions reduce nerve perfusion, but isolated elbow flexion does not have a significant impact. We hypothesize that elbow splints alone may not influence cubital tunnel perfusion but may only prevent direct compression of the ulnar nerve. Advising patients about upper extremity postures that should be avoided may be more effective.
Topics: Cubital Tunnel Syndrome; Elbow; Humans; Perfusion; Posture; Ulnar Nerve; Wrist
PubMed: 34453352
DOI: 10.1002/mus.27408 -
Proceedings of the National Academy of... Jan 2022Precise information on localized variations in blood circulation holds the key for noninvasive diagnostics and therapeutic assessment of various forms of cancer. While...
Precise information on localized variations in blood circulation holds the key for noninvasive diagnostics and therapeutic assessment of various forms of cancer. While thermal imaging by itself may provide significant insights on the combined implications of the relevant physiological parameters, viz. local blood perfusion and metabolic balance due to active tumors as well as the ambient conditions, knowledge of the tissue surface temperature alone may be somewhat inadequate in distinguishing between some ambiguous manifestations of precancer and cancerous lesions, resulting in compromise of the selectivity in detection. This, along with the lack of availability of a user-friendly and inexpensive portable device for thermal-image acquisition, blood perfusion mapping, and data integration acts as a deterrent against the emergence of an inexpensive, contact-free, and accurate in situ screening and diagnostic approach for cancer detection and management. Circumventing these constraints, here we report a portable noninvasive blood perfusion imager augmented with machine learning-based quantitative analytics for screening precancerous and cancerous traits in oral lesions, by probing the localized alterations in microcirculation. With a proven overall sensitivity >96.66% and specificity of 100% as compared to gold-standard biopsy-based tests, the method successfully classified oral cancer and precancer in a resource-limited clinical setting in a double-blinded patient trial and exhibited favorable predictive capabilities considering other complementary modes of medical image analysis as well. The method holds further potential to achieve contrast-free, accurate, and low-cost diagnosis of abnormal microvascular physiology and other clinically vulnerable conditions, when interpreted along with complementary clinically evidenced decision-making perspectives.
Topics: Adult; Aged, 80 and over; Algorithms; Biopsy; Diagnostic Imaging; Early Detection of Cancer; Humans; Image Processing, Computer-Assisted; Machine Learning; Male; Mass Screening; Middle Aged; Mouth Neoplasms; Perfusion; Squamous Cell Carcinoma of Head and Neck
PubMed: 34983869
DOI: 10.1073/pnas.2026201119 -
Experimental Eye Research Jul 2022The key risk factor for glaucoma is elevation of intraocular pressure (IOP) and alleviating it is the only effective therapeutic approach to inhibit further vision loss....
The key risk factor for glaucoma is elevation of intraocular pressure (IOP) and alleviating it is the only effective therapeutic approach to inhibit further vision loss. IOP is regulated by the flow of aqueous humour across resistive tissues, and a reduction in outflow facility, is responsible for the IOP elevation in glaucoma. Measurement of outflow facility is therefore important when investigating the pathophysiology of glaucoma and testing candidate treatments for lowering IOP. Due to similar anatomy and response to pharmacological treatments, mouse eyes are a common model of human aqueous humour dynamics. The ex vivo preparation, in which an enucleated mouse eye is mounted in a temperature controlled bath and cannulated, has been well characterised and is widely used. The postmortem in situ model, in which the eyes are perfused within the cadaver, has received relatively little attention. In this study, we investigate the postmortem in situ model using the iPerfusion system, with a particular focus on i) the presence or absence of pressure-independent flow, ii) the effect of evaporation on measured flow rates and iii) the magnitude and pressure dependence of outflow facility and how these properties are affected by postmortem changes. Measurements immediately after cannulation and following multi-pressure facility measurement demonstrated negligible pressure-independent flow in postmortem eyes, in contrast to assumptions made in previous studies. Using a humidity chamber, we investigated whether the humidity of the surrounding air would influence measured flow rates. We found that at room levels of humidity, evaporation of saline droplets on the eye resulted in artefactual flow rates with a magnitude comparable to outflow, which were eliminated by a high relative humidity (>85%) environment. Average postmortem outflow facility was ∼4 nl/min/mmHg, similar to values observed ex vivo, irrespective of whether a postmortem delay was introduced prior to cannulation. The intra-animal variability of measured outflow facility values was also reduced relative to previous ex vivo data. The pressure-dependence of outflow facility was reduced in the postmortem relative to ex vivo model, and practically eliminated when eyes were cannulated >40 min after euthanisation. Overall, our results indicate that the moderately increased technical complexity associated with postmortem perfusion provides reduced variability and reduced pressure-dependence in outflow facility, when experimental conditions are properly controlled.
Topics: Animals; Aqueous Humor; Glaucoma; Intraocular Pressure; Mice; Perfusion; Tonometry, Ocular; Trabecular Meshwork
PubMed: 35525299
DOI: 10.1016/j.exer.2022.109103 -
Scientific Reports Aug 2023We hypothesized that the association between BP and endovascular treatment (EVT) outcomes would differ by baseline perfusion and recanalization status. We identified 388...
We hypothesized that the association between BP and endovascular treatment (EVT) outcomes would differ by baseline perfusion and recanalization status. We identified 388 ICA or M1 occlusion patients who underwent EVT ≤ 24 h from onset with successful recanalization (TICI ≥ 2b). BP was measured at 5-min intervals from arrival and during the procedure. Systolic BPs (SBP) were summarized as dropmax (the maximal decrease over two consecutive measurements), incmax (the maximal increase), mean, coefficient of variation (cv), and standard deviation. Adequate baseline perfusion was defined as hypoperfusion intensity ratio (HIR) ≤ 0.5; infarct proportion as the volume ratio of final infarcts within the T > 6 s region. In the adequate perfusion group, infarct proportion was closely associated with SBP (β ± SE (P-value); 1.22 ± 0.48, (< 0.01)), SBP (1.12 ± 0.33, (< 0.01)), SBP (0.61 ± 0.15 (< 0.01)), SBP (0.66 ± 0.08 (< 0.01)), and SBP (0.71 ± 0.37 (0.053) before recanalization. The associations remained significant only in SBP, SBP, and SBP after recanalization. SBP, SBP and SBP showed significant associations with modified Rankin Scale score at 3 months in the pre-recanalization period. In the poor perfusion group, none of the SBP indices was associated with any stroke outcomes regardless of recanalization status. BP may show differential associations with stroke outcomes by the recanalization and baseline perfusion status.
Topics: Humans; Blood Pressure; Perfusion; Reperfusion; Stroke; Treatment Outcome
PubMed: 37612355
DOI: 10.1038/s41598-023-40572-0 -
Frontiers in Immunology 2023In response to the increasing demand for lung transplantation, lung perfusion (EVLP) has extended the number of suitable donor lungs by rehabilitating marginal organs....
In response to the increasing demand for lung transplantation, lung perfusion (EVLP) has extended the number of suitable donor lungs by rehabilitating marginal organs. However despite an expanding use in clinical practice, the responses of the different lung cell types to EVLP are not known. In order to advance our mechanistic understanding and establish a refine tool for improvement of EVLP, we conducted a pioneer study involving single cell RNA-seq on human lungs declined for transplantation. Functional enrichment analyses were performed upon integration of data sets generated at 4 h (clinical duration) and 10 h (prolonged duration) from two human lungs processed to EVLP. Pathways related to inflammation were predicted activated in epithelial and blood endothelial cells, in monocyte-derived macrophages and temporally at 4 h in alveolar macrophages. Pathways related to cytoskeleton signaling/organization were predicted reduced in most cell types mainly at 10 h. We identified a division of labor between cell types for the selected expression of cytokine and chemokine genes that varied according to time. Immune cells including CD4 and CD8 T cells, NK cells, mast cells and conventional dendritic cells displayed gene expression patterns indicating blunted activation, already at 4 h in several instances and further more at 10 h. Therefore despite inducing inflammatory responses, EVLP appears to dampen the activation of major lung immune cell types, what may be beneficial to the outcome of transplantation. Our results also support that therapeutics approaches aiming at reducing inflammation upon EVLP should target both the alveolar and vascular compartments.
Topics: Humans; Perfusion; CD8-Positive T-Lymphocytes; Endothelial Cells; Lung Transplantation; Lung; Inflammation
PubMed: 37465668
DOI: 10.3389/fimmu.2023.1142228 -
Frontiers in Immunology 2022Transplant centers around the world have been using extended criteria donors to remedy the ongoing demand for lung transplantation. With a rapidly aging population,... (Review)
Review
Transplant centers around the world have been using extended criteria donors to remedy the ongoing demand for lung transplantation. With a rapidly aging population, older donors are increasingly considered. Donor age, at the same time has been linked to higher rates of lung ischemia reperfusion injury (IRI). This process of acute, sterile inflammation occurring upon reperfusion is a key driver of primary graft dysfunction (PGD) leading to inferior short- and long-term survival. Understanding and improving the condition of older lungs is thus critical to optimize outcomes. Notably, lung perfusion (EVLP) seems to have the potential of reconditioning ischemic lungs through perfusing and ventilation. Here, we aim to delineate mechanisms driving lung IRI and review both experimental and clinical data on the effects of aging in augmenting the consequences of IRI and PGD in lung transplantation.
Topics: Aged; Humans; Lung; Perfusion; Primary Graft Dysfunction; Reperfusion Injury
PubMed: 35686120
DOI: 10.3389/fimmu.2022.891564