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American Journal of Veterinary Research Feb 2020To evaluate the feasibility of contrast-enhanced CT for assessment of pancreatic perfusion in healthy dogs.
OBJECTIVE
To evaluate the feasibility of contrast-enhanced CT for assessment of pancreatic perfusion in healthy dogs.
ANIMALS
6 healthy purpose-bred female Treeing Walker Coonhounds.
PROCEDURES
Contrast-enhanced CT of the cranial part of the abdomen was performed with 3-mm slice thickness. Postprocessing computer software designed for evaluation of human patients was used to calculate perfusion data for the pancreas and liver by use of 3-mm and reformatted 6-mm slices. Differences in perfusion variables between the pancreas and liver and differences in liver-specific data of interest were evaluated with the Friedman test.
RESULTS
Multiple pancreatic perfusion variables were determined, including perfusion, peak enhancement index, time to peak enhancement, and blood volume. The same variables as well as arterial, portal, and total perfusion and hepatic perfusion index were determined for the liver. Values for 6-mm slices appeared similar to those for 3-mm slices. The liver had significantly greater median perfusion and peak enhancement index, compared with the pancreas.
CONCLUSIONS AND CLINICAL RELEVANCE
Measurement of pancreatic perfusion with contrast-enhanced CT was feasible in this group of dogs. Hepatic arterial and pancreatic perfusion values were similar to previously published findings for dogs, but hepatic portal and hepatic total perfusion measurements were not. These discrepancies might have been attributable to physiologic differences between dogs and people and related limitations of the CT software intended for evaluation of human patients. Further research is warranted to assess reliability of perfusion variables and applicability of the method for assessment of canine patients with pancreatic abnormalities.
Topics: Animals; Contrast Media; Dogs; Female; Humans; Liver; Pancreas; Perfusion; Reproducibility of Results; Tomography, X-Ray Computed
PubMed: 31985282
DOI: 10.2460/ajvr.81.2.131 -
Journal of Applied Physiology... Nov 2021In recent years, it has become common to experiment with ex vivo perfused lungs for organ transplantation and to attempt regenerative pulmonary engineering using...
In recent years, it has become common to experiment with ex vivo perfused lungs for organ transplantation and to attempt regenerative pulmonary engineering using decellularized lung matrices. However, our understanding of the physiology of ex vivo organ perfusion is imperfect; it is not currently well understood how decreasing microvascular barrier affects the perfusion of pulmonary parenchyma. In addition, protocols for lung perfusion and organ culture fluid-handling are far from standardized, with widespread variation on both basic methods and on ideally controlled parameters. To address both of these deficits, a robust, noninvasive, and mechanistic model is needed which is able to predict microvascular resistance and permeability in perfused lungs while providing insight into capillary recruitment. Although validated mathematical models exist for fluid flow in native pulmonary tissue, previous models generally assume minimal intravascular leak from artery to vein and do not assess capillary bed recruitment. Such models are difficult to apply to both ex vivo lung perfusions, in which edema can develop over time and microvessels can become blocked, and to decellularized ex vivo organomimetic cultures, in which microvascular recruitment is variable and arterially perfused fluid enters into the alveolar space. Here, we develop a mathematical model of pulmonary microvascular fluid flow which is applicable in both instances, and we apply our model to data from native, decellularized, and regenerating lungs under ex vivo perfusion. The results provide substantial insight into microvascular pressure-flow mechanics, while producing previously unknown output values for tissue-specific capillary-alveolar hydraulic conductivity, microvascular recruitment, and total organ barrier resistance. We present a validated model of pulmonary microvascular fluid mechanics and apply this model to study the effects of increased capillary permeability in decellularized and regenerating lungs. We find that decellularization alters microvascular steady-state mechanics and that re-endothelialization partially rescues key biologic parameters. The described model provides powerful insight into intraorgan microvascular dynamics and may be used to guide regenerative engineering experiments. We include all data and derivations necessary to replicate this work.
Topics: Capillaries; Lung; Microvessels; Perfusion
PubMed: 34554016
DOI: 10.1152/japplphysiol.00286.2020 -
International Journal of Molecular... May 2021Transplantation represents the treatment of choice for many end-stage diseases but is limited by the shortage of healthy donor organs. Ex situ normothermic machine... (Review)
Review
Transplantation represents the treatment of choice for many end-stage diseases but is limited by the shortage of healthy donor organs. Ex situ normothermic machine perfusion (NMP) has the potential to extend the donor pool by facilitating the use of marginal quality organs such as those from donors after cardiac death (DCD) and extended criteria donors (ECD). NMP provides a platform for organ quality assessment but also offers the opportunity to treat and eventually regenerate organs during the perfusion process prior to transplantation. Due to their anti-inflammatory, immunomodulatory and regenerative capacity, mesenchymal stem cells (MSCs) are considered as an interesting tool in this model system. Only a limited number of studies have reported on the use of MSCs during ex situ machine perfusion so far with a focus on feasibility and safety aspects. At this point, no clinical benefits have been conclusively demonstrated, and studies with controlled transplantation set-ups are urgently warranted to elucidate favorable effects of MSCs in order to improve organs during ex situ machine perfusion.
Topics: Animals; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Organ Preservation; Organ Transplantation; Perfusion; Regenerative Medicine; Time Factors; Tissue Donors; Tissue and Organ Procurement
PubMed: 34063399
DOI: 10.3390/ijms22105233 -
Current Opinion in Organ Transplantation Jun 2022Significant limitations in organ availability and postoperative graft dysfunction plague lung transplantation and there is continual need for innovation. Ex-vivo lung... (Review)
Review
PURPOSE OF REVIEW
Significant limitations in organ availability and postoperative graft dysfunction plague lung transplantation and there is continual need for innovation. Ex-vivo lung perfusion (EVLP) has emerged over the last decade as an alternative and/or complementary allograft storage and assessment tool, however logistical hurdles have limited its widespread dissemination. As such, the overall current and potential value of EVLP on modern-day lung transplantation should be considered as innovation moves forward.
RECENT FINDINGS
Since inception, EVLP has made important safety strides in conclusively showing noninferiority to cold storage in several trials. Recent advances have highlighted potential mechanisms by which EVLP in its current form may reduce the pathogenic origins of primary graft dysfunction. Exciting work on organ reconditioning with EVLP via reduction in intermediaries of acute inflammation and oxidative stress have been performed in animal models. In addition, cross-circulation during EVLP has emerged as a method to achieve more prolonged ex situ storage. The impending translation of these to clinical use will markedly improve the overall value of EVLP.
SUMMARY
This review will highlight the current status of EVLP as it pertains to overall value in lung transplantation, focusing on historical and recent preclinical work and how innovation therein will improve lung transplantation as a field.
Topics: Animals; Extracorporeal Circulation; Humans; Lung; Lung Transplantation; Perfusion; Tissue and Organ Procurement
PubMed: 35649110
DOI: 10.1097/MOT.0000000000000961 -
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 -
Hearing Research Jul 2016The flow of viscous fluid in the cochlea induces shear forces, which could provide benefit in clinical practice, for example to guide cochlear implant insertion or...
The flow of viscous fluid in the cochlea induces shear forces, which could provide benefit in clinical practice, for example to guide cochlear implant insertion or produce static pressure to the cochlear partition or wall. From a research standpoint, studying the effects of a viscous fluid in the cochlea provides data for better understanding cochlear fluid mechanics. However, cochlear perfusion with a viscous fluid may damage the cochlea. In this work we studied the physiological and anatomical effects of perfusing the cochlea with a viscous fluid. Gerbil cochleae were perfused at a rate of 2.4 μL/min with artificial perilymph (AP) and sodium hyaluronate (Healon, HA) in four different concentrations (0.0625%, 0.125%, 0.25%, 0.5%). The different HA concentrations were applied either sequentially in the same cochlea or individually in different cochleae. The perfusion fluid entered from the round window and was withdrawn from basal scala vestibuli, in order to perfuse the entire perilymphatic space. Compound action potentials (CAP) were measured after each perfusion. After perfusion with increasing concentrations of HA in the order of increasing viscosity, the CAP thresholds generally increased. The threshold elevation after AP and 0.0625% HA perfusion was small or almost zero, and the 0.125% HA was a borderline case, while the higher concentrations significantly elevated CAP thresholds. Histology of the cochleae perfused with the 0.0625% HA showed an intact Reissner's membrane (RM), while in cochleae perfused with 0.125% and 0.25% HA RM was torn. Thus, the CAP threshold elevation was likely due to the broken RM, likely caused by the shear stress produced by the flow of the viscous fluid. Our results and analysis indicate that the cochlea can sustain, without a significant CAP threshold shift, up to a 1.5 Pa shear stress. Beside these finding, in the 0.125% and 0.25% HA perfusion cases, a temporary CAP threshold shift was observed, perhaps due to the presence and then clearance of viscous fluid within the cochlea, or to a temporary position shift of the Organ of Corti. After 0.5% HA perfusion, a short latency positive peak (P0) appeared in the CAP waveform. This P0 might be due to a change in the cochlea's traveling-wave pattern, or distortion in the cochlear microphonic.
Topics: Action Potentials; Animals; Cochlea; Cochlear Duct; Cochlear Implantation; Cochlear Implants; Cochlear Microphonic Potentials; Female; Gerbillinae; Hyaluronic Acid; Organ of Corti; Perfusion; Perilymph; Round Window, Ear; Scala Vestibuli; Shear Strength; Viscosity
PubMed: 27220484
DOI: 10.1016/j.heares.2016.05.007 -
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 2021Although solid organ transplantation remains the definitive management for patients with end-stage organ failure, this ultimate treatment has been limited by the number... (Review)
Review
Although solid organ transplantation remains the definitive management for patients with end-stage organ failure, this ultimate treatment has been limited by the number of acceptable donor organs. Therefore, efforts have been made to expand the donor pool by utilizing marginal organs from donation after circulatory death or extended criteria donors. However, marginal organs are susceptible to ischemia-reperfusion injury (IRI) and entail higher requirements for organ preservation. Recently, machine perfusion has emerged as a novel preservation strategy for marginal grafts. This technique continually perfuses the organs to mimic the physiologic condition, allows the evaluation of pretransplant graft function, and more excitingly facilitates organ reconditioning during perfusion with pharmacological, gene, and stem cell therapy. As mesenchymal stem cells (MSCs) have anti-oxidative, immunomodulatory, and regenerative properties, mounting studies have demonstrated the therapeutic effects of MSCs on organ IRI and solid organ transplantation. Therefore, MSCs are promising candidates for organ reconditioning during machine perfusion. This review provides an overview of the application of MSCs combined with machine perfusion for lung, kidney, liver, and heart preservation and reconditioning. Promising preclinical results highlight the potential clinical translation of this innovative strategy to improve the quality of marginal grafts.
Topics: Animals; Humans; Mesenchymal Stem Cells; Organ Preservation; Perfusion
PubMed: 35024039
DOI: 10.3389/fimmu.2021.713920 -
Current Opinion in Organ Transplantation Oct 2018In this review, we discuss novel strategies that allow for extended preservation of vascularized composite allografts and their potential future clinical implications... (Review)
Review
PURPOSE OF REVIEW
In this review, we discuss novel strategies that allow for extended preservation of vascularized composite allografts and their potential future clinical implications for the field of vascularized composite allotransplantation (VCA).
RECENT FINDINGS
The current gold standard in tissue preservation - static cold preservation on ice - is insufficient to preserve VCA grafts for more than a few hours. Advancements in the field of VCA regarding matching and allocation, desensitization, and potential tolerance induction are all within reasonable reach to achieve; these are, however, constrained by limited preservation time of VCA grafts. Although machine perfusion holds many advantages over static cold preservation, it currently does not elongate the preservation time. More extreme preservation techniques, such as cryopreservation approaches, are, however, specifically difficult to apply to composite tissues as the susceptibility to ischemia and cryoprotectant agents varies greatly by tissue type.
SUMMARY
In the current scope of extended preservation protocols, high subzero approaches of VCA grafts will be particularly critical enabling technologies for the implementation of tolerance protocols clinically. Ultimately, advances in both preservation techniques and tolerance induction have the potential to transform the field of VCA and eventually lead to broad applications in reconstructive transplantation.
Topics: Cryobiology; Humans; Organ Preservation; Perfusion; Vascularized Composite Allotransplantation
PubMed: 30080697
DOI: 10.1097/MOT.0000000000000567