Effectiveness of metformin for the reversal of cold-ischemia-induced damage in hepatosteatosis.

BACKGROUND: Primary dysfunction and rejection are more common in donor liver tissues with steatosis. AMP-activated protein kinase (AMPK) assumes organ-protective functions during ischemia. Metformin was used for the activation of AMPK in hepatocytes. The aim of this study is to investigate the effectiveness of metformin administration for the reversal of cold-ischemia-induced damage in hepatosteatosis. MATERIAL AND METHODS: Seven-week-old C7BL56 male-mice (n = 109) were separated into four groups depending on diet type and metformin use. A specific diet model was followed for 10 weeks to induce hepatosteatosis. A group of the animals was administered with metformin for the last four weeks via oral gavage. After resection, the liver tissues were perfused and kept for 0-6-12-24 h in the UW solution. Histopathological examinations were performed, and Western blot was utilized to analyze p-AMPK and AMPK expression levels. RESULTS: Hepatosteatosis decreased significantly with metformin. The steatotic liver group had more prominent pericentral inflammation, necrosis as well as showing a decreased and more delayed AMPK response than the non-fat group. All these alterations could be corrected using metformin. CONCLUSION: Metformin can increase the resistance of livers with hepatosteatosis to cold-ischemia-induced damage, which in turn may pave the way for successful transplantation of fatty living-donor livers.

Effect of PERLA®, a new cold-storage solution, on oxidative stress injury and early graft function in rat kidney transplantation model.

BACKGROUND: The composition of organ preservation solutions is crucial for maintaining graft integrity and early graft function after transplantation. The aim of this study is to compare new organ preservation solution PERLA® with the gold standard preservation solution University of Wisconsin (UW) regarding oxidative stress and early graft injury. METHODS: In order to assess oxidative stress after cold storage, kidney grafts have been preserved for 18 h at 4° C in either UW solution or PERLA® solution and then assessed for oxidative stress injury (protocol 1). To assess kidney injuries and oxidative stress after reperfusion, rat kidneys were harvested, stored in cold UW or in PERLA® solutions for 18 h at 4 °C and then transplanted heterotopically for 6 h (protocol 2). PERLA® is a high Na+/low K+ solution including PEG-35 (1 g/L), trimetazidine (1 µM), carvedilol (10 µM) and tacrolimus (5 µM). RESULTS: Our results showed that preservation of kidneys in PERLA® solution significantly attenuates oxidative stress parameters after cold storage and reperfusion. We found a significant decrease in oxidative damage indicators (MDA, CD and CP) and a significant increase in antioxidant indicators (GPx, GSH, CAT, SOD and PSH). Moreover, PERLA® solution decreased kidney injury after reperfusion (creatinine, LDH and uric acid). CONCLUSION: PERLA® solution was more effective than UW storage solution in preserving rat's kidney grafts.

Prolonged cold-preservation of domestic cat ovarian tissue is improved by extracellular solution but impaired by the fragmentation of ovary.

For domestic cats ovaries, recommended cold-storage limit is 24 h in Phosphate Buffered Saline (PBS) or Dulbecco`s PBS (DPBS). Here, we attempted to verify wheatear cat ovaries may benefit from more complex solutions during prolonged cold-storage (>24 h). First, the preservation capabilities of extracellular (SP+), intracellular (UW) solutions and DPBS supplemented with glutathione (DPBS+GSH) were compared using ovary fragments from the same ovary (n=10). Intact ovary stored in DPBS served as a control. Ovaries were kept at 4 °C for 48 h, and 72 h. In the second experiment, first ovary was stored in DPBS, second in SP+ or UW solution for 48 h (n = 12). Ovaries pairs stored in DPBS for 24 h served as a control (n=8). Tissue samples were evaluated directly after cold-storage and after following 24 h in vitro culture. Ovarian follicle morphology, apoptosis rates (cleaved caspase-3, TUNEL), and follicular growth activation (Ki-67) were assessed. Ovary fragmentation impaired follicular morphology preservation upon cold-storage comparing to intact ovary. However, ovarian fragments stored in UW for 48 h and in SP+ for 72 h presented better morphology than DPBS+GSH group. Comparison of intact ovaries cold-storage for 48 h showed that SP+ provided superior follicular morphology over DPBS, and it was comparable to the outcome of 24-hour storage. No follicular activation after in vitro culture was observed. Nevertheless, tissue culture increased considerably caspase-3 cleavage and TUNEL detection. The ovary fragmentation prior to cold-storage is not recommended in domestic cats. Replacement of DPBS with SP+ solution for whole ovary and UW solution for ovarian tissue fragments improves follicular structure preservation during 48-hour cold-storage.

Modification of Preservative Fluids with Antioxidants in Terms of Their Efficacy in Liver Protection before Transplantation.

Transplantation is currently the only effective treatment for patients with end-stage liver failure. In recent years, many advanced studies have been conducted to improve the efficiency of organ preservation techniques. Modifying the composition of the preservation fluids currently used may improve graft function and increase the likelihood of transplantation success. The modified fluid is expected to extend the period of safe liver storage in the peri-transplantation period and to increase the pool of organs for transplantation with livers from marginal donors. This paper provides a literature review of the effects of antioxidants on the efficacy of liver preservation fluids. Medline (PubMed), Scopus, and Cochrane Library databases were searched using a combination of MeSH terms: "liver preservation", "transplantation", "preservation solution", "antioxidant", "cold storage", "mechanical perfusion", "oxidative stress", "ischemia-reperfusion injury". Studies published up to December 2023 were included in the analysis, with a focus on publications from the last 30 years. A total of 45 studies met the inclusion criteria. The chemical compounds analyzed showed mostly bioprotective effects on hepatocytes, including but not limited to multifactorial antioxidant and free radical protective effects. It should be noted that most of the information cited is from reports of studies conducted in animal models, most of them in rodents.

Significantly Improved Cold Preservation of Rat Hind Limb Vascularized Composite Allografts Using the New PrC-210 Free Radical Scavenger.

Vascularized composite allotransplantation (VCA) represents a promising reconstructive solution primarily conducted to improve quality of life. However, tissue damage caused by cold-ischemia (CI) storage prior to transplant represents a major factor limiting widespread application. This study investigates the addition of the novel free radical scavenger PrC-210 to UW Organ Preservation Solution (UW Solution) to suppress CI-induced skeletal muscle injury in a rat hind limb amputation model. Lewis rats received systemic perfusion of UW solution +/- PrC-210 (0 mM control, 10 mM, 20 mM, 30 mM, or 40 mM), followed by bilateral transfemoral amputation. Limbs were stored in 40 mL of the same perfusate at 4 °C for 48 h. Muscle punch biopsies were taken at set times over the 48 h cold-storage period and analyzed for caspase-3,7 activity, cytochrome C levels, and qualitative histology. A single 15 s perfusion of PrC-210-containing UW Solution conferred a dose-dependent reduction in CI-induced muscle cell death over 48 h. In the presence of PrC-210, muscle cell mitochondrial cytochrome C release was equivalent to 0 h controls, with profound reductions in the caspase-3,7 apoptotic marker that correlated with limb histology. PrC-210 conferred complete prevention of ROS-induced mitochondrial lysis in vitro, as measured by cytochrome C release. We conclude that the addition of 30 mM PrC210 to UW Solution conferred the most consistent reduction in CI limb damage, and it warrants further investigation for clinical application in the VCA setting.

Important Constituents of Heavy Water-containing Solution for Cold Storage and Subsequent Reperfusion on an Isolated Perfused Rat Liver.

The University of Wisconsin (UW) solution is the most effective preservation solution currently used; however, to safely use expanded-criteria donor grafts, a new cold storage solution that alleviates graft injury more effectively is required. We prepared a heavy water (D2O)-containing buffer, Dsol, and observed strong protective effects during extended cold storage of rat hearts and livers. In the current study, we modified Dsol (mDsol) and tested its efficacy. The aim of the present study was to determine whether mDsol could protect the rat liver more effectively than the UW solution and to clarify the roles of D2O and deferoxamine (DFX). Rat livers were subjected to cold storage for 48 hours in test solutions: UW, mDsol, mDsol without D2O or DFX (mDsol-D2O[-], mDsol-DFX[-]), and subsequently reperfused on an isolated perfused rat liver for 90 minutes at 37°C. In the UW group, the liver was dehydrated during cold storage and rapidly expanded during reperfusion. Accordingly, the cumulative weight change was the highest in the UW group, together with augmented portal veinous resistance and ALT leakage and decreased oxygen consumption rate and bile production. These changes were significantly suppressed in the mDsol-treated group. In the mDsol-D2O(-) and mDsol-DFX(-) groups offered partial protection. In conclusion, mDsol appeared to be superior to the UW solution for simple cold storage of the rat liver, presumably due to improved microcirculation in the early phase of reperfusion. Both heavy water and deferoxamine are essential for alleviating seamless organ swelling that occurs during cold storage and subsequent reperfusion.

Improved cardioprotective effect of 3-nitro-N-methyl salicylamide solution after a prolonged preservation time of rat heart.

Ischemic reperfusion injury, caused by oxidative stress during reperfusion, is an inevitable outcome of organ transplantation, especially when the organ preservation time is prolonged. Prolonged ischaemic preservation is a valuable technique for improving the success of organ transplantation, but numerous challenges remain. 3-nitro-N-methyl salicylamide (3-NNMS), an inhibitor of mitochondrial electron transport chain complex III, can be used to reduce reactive oxygen species production during blood reperfusion by slowing the electron flow rate of the respiratory chain. Based on this property, a novel preservation solution was developed for the preservation of isolated rat heart and its cardioprotective effect was investigated during an 8-h cold ischaemia preservation time for the first time. For comparison, 3-NNMS was also included in the histidine-tryptophan-ketoglutarate (HTK) solution. Compared to HTK, HTK supplemented with 3-NNMS significantly improved the heart rate of isolated rat hearts after 8 h of cold storage. Both 3-NNMS solution and HTK supplemented with 3-NNMS solution decreased cardiac troponin T and lactate dehydrogenase levels in perfusion fluid and reduced reactive oxygen species and malondialdehyde levels in the myocardium. The 3-NNMS also maintained the membrane potential of myocardial mitochondria and significantly increased superoxide dismutase levels. These results showed that the new 3-NNMS solution can protect mitochondrial and cardiomyocyte function by increasing antioxidant capacity and reducing oxidative stress in cryopreserved rat hearts during a prolonged preservation time, resulting in less myocardial injury and better heart rate.

A Single Preservation Solution for Static Cold Storage and Hypothermic Oxygenated Perfusion of Marginal Liver Grafts: A Preclinical Study.

BACKGROUND: Hypothermic oxygenated perfusion (HOPE) improves outcomes of marginal liver grafts. However, to date, no preservation solution exists for both static cold storage (SCS) and HOPE. METHODS: After 30 min of asystolic warm ischemia, porcine livers underwent 6 h of SCS followed by 2 h of HOPE. Liver grafts were either preserved with a single preservation solution (IGL2) designed for SCS and HOPE (IGL2-Machine Perfusion Solution [MPS] group, n = 6) or with the gold-standard University of Wisconsin designed for for SCS and Belzer MPS designed for HOPE (MPS group, n = 5). All liver grafts underwent warm reperfusion with whole autologous blood for 2 h, and surrogate markers of hepatic ischemia-reperfusion injury (IRI) were assessed in the hepatocyte, cholangiocyte, vascular, and immunological compartments. RESULTS: After 2 h of warm reperfusion, livers in the IGL2-MPS group showed no significant differences in transaminase release (aspartate aminotransferase: 65.58 versus 104.9 UI/L/100 g liver; P = 0.178), lactate clearance, and histological IRI compared with livers in the MPS group. There were no significant differences in biliary acid composition, bile production, and histological biliary IRI. Mitochondrial and endothelial damage was also not significantly different and resulted in similar hepatic inflammasome activation. CONCLUSIONS: This preclinical study shows that a novel IGL2 allows for the safe preservation of marginal liver grafts with SCS and HOPE. Hepatic IRI was comparable with the current gold standard of combining 2 different preservation solutions (University of Wisconsin + Belzer MPS). These data pave the way for a phase I first-in-human study and it is a first step toward tailored preservation solutions for machine perfusion of liver grafts.

CPA toxicity screening of cryoprotective solutions in rat hearts.

In clinical practice, donor hearts are transported on ice prior to transplant and discarded if cold ischemia time exceeds ∼5 h. Methods to extend these preservation times are critically needed, and ideally, this storage time would extend indefinitely, enabling improved donor-to-patient matching, organ utilization, and immune tolerance induction protocols. Previously, we demonstrated successful vitrification and rewarming of whole rat hearts without ice formation by perfusion-loading a cryoprotective agent (CPA) solution prior to vitrification. However, these hearts did not recover any beating even in controls with CPA loading/unloading alone, which points to the chemical toxicity of the cryoprotective solution (VS55 in Euro-Collins carrier solution) as the likely culprit. To address this, we compared the toxicity of another established CPA cocktail (VEG) to VS55 using ex situ rat heart perfusion. The CPA exposure time was 150 min, and the normothermic assessment time was 60 min. Using Celsior as the carrier, we observed partial recovery of function (atria-only beating) for both VS55 and VEG. Upon further analysis, we found that the VEG CPA cocktail resulted in 50 % lower LDH release than VS55 (N = 4, p = 0.017), suggesting VEG has lower toxicity than VS55. Celsior was a better carrier solution than alternatives such as UW, as CPA + Celsior-treated hearts spent less time in cardiac arrest (N = 4, p = 0.029). While we showed substantial improvement in cardiac function after exposure to vitrifiable concentrations of CPA by improving both the CPA and carrier solution formulation, further improvements will be required before we achieve healthy cryopreserved organs for transplant.

Association of cardiac preservation solution with short-term outcomes after heart transplantation.

AIMS: There is wide variability in the practice of cardiac preservation for heart transplantation. Prior reports suggest that the type of solution may be linked with a reduced incidence of posttransplantation complications. METHODS: Adult (≥18 years old) heart recipients who underwent transplantation between 2015 and 2021 in the United States were examined. Recipients were stratified by solution utilized for their grafts at the time of recovery: University of Wisconsin, histidine-tryptophan-ketoglutarate (HTK), or Celsior solution. The primary endpoint was a composite of 30-day mortality, primary graft dysfunction, or re-transplantation. Risk adjustment was performed for the recipient, donor, and procedural characteristics using regression modeling. RESULTS: Among 16 884 recipients, the group distribution was University of Wisconsin solution 53%, HTK 22%, Celsior solution 15%, and other 10%. The observed incidence of the composite endpoint (University of Wisconsin solution = 3.6%, HTK = 4.0%, Celsior solution = 3.7%, P = 0.301) and 1-year survival (University of Wisconsin solution = 91.7%, HTK = 91.3%, Celsior solution = 91.7%, log-rank P = 0.777) were similar between groups. After adjustment, HTK was associated with a higher risk of the composite endpoint [odds ratio (OR) 1.249, 95% confidence interval (CI) 1.019-1.525, P = 0.030] in reference to University of Wisconsin solution. This association was substantially increased among recipients with ischemic periods of greater than 4 h (OR 1.817, 95% CI 1.188-2.730, P = 0.005). The risks were similar between University of Wisconsin solution and Celsior solution (P = 0.454). CONCLUSION: The use of the histidine-tryptophan-ketoglutarate solution during cold static storage for cardiac preservation is associated with increased rates of early mortality or primary graft dysfunction. Clinician discretion should guide its use, especially when prolonged ischemic times (>4 h) are anticipated.

Preservation Efficacy of a Quercetin and Sucrose Solution for Warm Ischemically Damaged Porcine Liver Grafts.

BACKGROUND: The University of Wisconsin (UW) solution is the gold standard for preserving the liver, kidneys, and pancreas. For renal preservation, the addition of the flavonoid, quercetin (QE), to the preservation solution reduces damage to renal tubular cells, and the addition of sucrose (Suc) is also beneficial for preservation. The aim of this study was to investigate the protective effects of QE and Suc on porcine livers in terms of warm and cold injury and to evaluate whether their use improves ischemia-reperfusion (I/R) injury after simple cold storage (CS). METHODS: We tested porcine livers procured after 30 minutes of warm ischemia followed by preservation for 6 hours under the following 2 conditions: group 1, preserved with the CS/UW solution (n = 4); group 2, preserved with the CS/UW solution containing Que 33.1 µM and Suc 0.1 M (n = 6). All livers were evaluated using an ex vivo isolated liver reperfusion model with saline-diluted autologous blood. RESULTS: Aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase levels in group 2 were significantly lower at 30 minutes of reperfusion than in group 1. Furthermore, histologic evaluation by hematoxylin and eosin staining showed significantly fewer morphologic changes in group 2 than in group 1, as indicated by the total Suzuki score. Group 2 also had significantly better scores for sinusoidal congestion and hepatocyte cytoplasmic vacuolization. CONCLUSION: Adding Que and Suc to the UW solution can effectively prevent cold injury in livers donated after circulatory death.

Deceased Donor Flush Volume Similar for Histidine-Tryptophan-Ketoglutarate and University of Wisconsin at a Single US Organ Procurement Organization: Adult and Pediatric Data.

BACKGROUND: Histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW) solutions are the two primary solid-organ preservation solutions used in the United States (>95%), but flush volumes vary markedly by region and center. This study analyzes data from a single organ procurement organization (OPO) to determine the actual clinical flush volumes used for HTK and UW for liver and pancreas grafts. METHODS: All procurements at Indiana Donor Network were analyzed (2016-2020), and data were extracted from the on-site records. Variables included procuring center, solution, volumes, and vessels flushed. Brand and generic versions were considered equivalent. No clinical transplant outcomes were available. RESULTS: Data were analyzed from 875 liver and 192 pancreas procurements by over 70 U.S. centers representing 10 of 11 UNOS regions. The large majority of liver grafts were preserved with HTK (n=810, 93%; UW n=93, 7%). All liver donors received an aortic flush (100%), while portal vein flush was 14% in-situ and 88% back table. For liver grafts, the median volume of infused solution was less for HTK when compared to UW (4225mL vs 5500mL, p=0.04). For pancreas procurement, 100% received aortic flush of the graft, with median HTK and UW volumes being equivalent (3000mL; p=0.85). Pediatric organs were flushed with markedly higher weight-based volumes. CONCLUSIONS: Flush volumes for HTK and UW are similar at one midwestern OPO, with data comprised of procurements performed by centers from across the U.S. These data demonstrate that low-volume HTK flush is commonly used, and this practice may be considered as a cost-saving measure.

Preservation solution Custodiol containing human alpha-1-antitrypsin improves graft recovery after prolonged cold ischemic storage in a rat model of heart transplantation.

Introduction: The shortage of available donor hearts and the risk of ischemia/reperfusion injury restrict heart transplantation (HTX). Alpha-1-antitrypsin (AAT), a well-characterized inhibitor of neutrophil serine protease, is used in augmentation therapy to treat emphysema due to severe AAT deficiency. Evidence demonstrates its additional anti-inflammatory and tissue-protective effects. We hypothesized that adding human AAT in a preservation solution reduces graft dysfunction in a rat model of HTX following extended cold ischemic storage. Methods: The hearts from isogenic Lewis donor rats were explanted, stored for either 1h or 5h in cold Custodiol supplemented with either vehicle (1h ischemia, n=7 or 5h ischemia, n=7 groups) or 1 mg/ml AAT (1h ischemia+AAT, n=7 or 5h ischemia+AAT, n=9 groups) before heterotopic HTX. Left-ventricular (LV) graft function was evaluated in vivo 1.5h after HTX. Immunohistochemical detection of myeloperoxydase (MPO) was performed in myocardial tissue and expression of 88 gene quantified with PCR was analyzed both statistical and with machine-learning methods. Results: After HTX, LV systolic function (dP/dtmax 1h ischemia+AAT 4197 ± 256 vs 1h ischemia 3123 ± 110; 5h ischemia+AAT 2858 ± 154 vs 5h ischemia 1843 ± 104mmHg/s, p<0.05) and diastolic function (dP/dtmin 5h ischemia+AAT 1516 ± 68 vs 5h ischemia 1095 ± 67mmHg/s, p<0.05) at an intraventricular volume of 90µl were improved in the AAT groups compared with the corresponding vehicle groups. In addition, the rate pressure product (1h ischemia+AAT 53 ± 4 vs 1h ischemia 26 ± 1; 5h ischemia+AAT 37 ± 3 vs 5h ischemia 21 ± 1mmHg*beats/min at an intraventricular volume of 90µl; p<0.05) was increased in the AAT groups compared with the corresponding vehicle groups. Moreover, the 5h ischemia+AAT hearts exhibited a significant reduction in MPO-positive cell infiltration in comparison to the 5h ischemia group. Our computational analysis shows that ischemia+AAT network displays higher homogeneity, more positive and fewer negative gene correlations than the ischemia+placebo network. Discussion: We provided experimental evidence that AAT protects cardiac grafts from prolonged cold ischemia during HTX in rats.

Combination of Cold Storage in a Heavy Water-Containing Solution and Post-Reperfusion Hydrogen Gas Treatment Reduces Ischemia-Reperfusion Injury in Rat Livers.

We previously reported the efficacy of cold storage (CS) using a heavy water-containing solution (Dsol) and post-reperfusion hydrogen gas treatment separately. This study aimed to clarify the combined effects of these treatments. Rat livers were subjected to 48-hour CS and a subsequent 90-minute reperfusion in an isolated perfused rat liver system. The experimental groups were the immediately reperfused control group (CT), the CS with University of Wisconsin solution (UW) group, the CS with Dsol group, the CS with UW and post-reperfusion H2 treatment group (UW-H2), and the CS with Dsol and post-reperfusion H2 group (Dsol-H2). We first compared the Dsol-H2, UW, and CT groups to evaluate this alternative method to conventional CS. The protective potential of the Dsol-H2 group was superior to that of the UW group, as evidenced by lower portal venous resistance and lactate dehydrogenase leakage, a higher oxygen consumption rate, and increased bile production. Multiple comparison tests among the UW, Dsol, UW-H2, and Dsol-H2 groups revealed that both treatments, during CS and after reperfusion, conferred a similar extent of protection and showed additive effects in combination therapy. Furthermore, the variance in all treatment groups appeared smaller than that in the no-treatment or no-stress groups, with excellent reproducibility. In conclusion, combination therapy with Dsol during CS and hydrogen gas after reperfusion additively protects against graft injury.

Chilling injury in human kidney tubule cells after subzero storage is not mitigated by antifreeze protein addition.

By preventing freezing, antifreeze proteins (AFPs) can permit cells and organs to be stored at subzero temperatures. As metabolic rates decrease with decreasing temperature, subzero static cold storage (SZ-SCS) could provide more time for tissue matching and potentially lead to fewer discarded organs. Human kidneys are generally stored for under 24 h and the tubule epithelium is known to be particularly sensitive to static cold storage (SCS). Here, telomerase-immortalized proximal-tubule epithelial cells from humans, which closely resemble their progenitors, were used as a proxy to assess the potential benefit of SZ-SCS for kidneys. The effects of hyperactive AFPs from a beetle and Cryostasis Storage Solution were compared to University of Wisconsin Solution at standard SCS temperatures (4 °C) and at -6 °C for up to six days. Although the AFPs helped guard against freezing, lower storage temperatures under these conditions were not beneficial. Compared to cells at 4 °C, those stored at -6 °C showed decreased viability as well as increased lactate dehydrogenase release and apoptosis. This suggests that this kidney cell type might be prone to chilling injury and that the addition of AFPs to enable SZ-SCS may not be effective for increasing storage times.

Protective effects of diclofenac on liver graft preservation.

This study aims to evaluate the effect of diclofenac addition to the preservation solution Celsior on liver graft preservation. Liver from Wistar rats were cold flushed in situ, harvested, and then stored in Celsior solution (24 h, 4 °C) supplemented or not with 50 mg/L of diclofenac sodium salt. Reperfusion was performed (120 min, 37 °C) using the isolated perfusion rat liver model. Perfusate samples were collected to evaluate transaminases' activities after cold storage and by the end of reperfusion. To evaluate liver function, bile flow, hepatic clearance of bromosulfophthalein, and vascular resistance were assessed. Diclofenac scavenging property (DPPH assay) as well as oxidative stress parameters (SOD and MPO activities and the concentration of glutathione, conjugated dienes, MDA, and carbonylated proteins) were measured. Transcription factors (PPAR-γ and NF-κB), inflammation (COX-2, IL-6, HMGB-1, and TLR-4), as well as apoptosis markers (Bcl-2 and Bax) were determined by quantitative RT-PCR. Enriching the preservation solution Celsior with diclofenac sodium salt attenuated liver injuries and improved graft function. Oxidative stress, inflammation, and apoptosis were significantly reduced in Celsior + Diclo solution. Also, diclofenac activated PPAR-γ and inhibited NF-κB transcription factors. To decrease graft damage and improve transplant recovery, diclofenac sodium salt may be a promising additive to preservation solution.

Evaluation of a Novel Graft-Holding Solution in Hair Transplantation: A Randomized Controlled Clinical Study.

BACKGROUND: Hair transplantation has become a popular choice for alopecia treatment; however, postsurgical hair shedding still annoys both patients and surgeons. OBJECTIVE: To explore the impact of graft-holding solution on postsurgical hair shedding and testify the protective efficacy of histidine-tryptophan-ketoglutarate solution with adenosine triphosphate and deferoxamine (HTK-AD). METHODS: There were 240 patients enrolled in the study, and the follicles were placed into either HTK-AD or Ringer solution (RS). Masson staining and live/dead staining were performed to evaluate graft morphology and apoptosis levels, respectively. The between-group comparison of postsurgical graft shedding, survival rate, complications, and patient satisfaction was performed. RESULTS: Grafts in HTK-AD maintained organized dense collagen construction and higher cell viability, but those preserved in RS became soft, which hindered implantation. Histidine-tryptophan-ketoglutarate solution with adenosine triphosphate and deferoxamine significantly reduced the incidence of postsurgical hair shedding (73.81% vs 95%), delayed shedding onset, and diminished shedding amount versus RS ( p < .05) when ≥3,000 grafts were transplanted. The shedding duration was shortened, and hair regrowth started earlier in HTK-AD versus RS ( p < .05); thus, satisfaction was increased. The final survival rate showed no difference between 2 groups. CONCLUSION: Histidine-tryptophan-ketoglutarate solution with adenosine triphosphate and deferoxamine is superior to RS for hair graft preservation because it improves graft viability and alleviates postsurgical shedding.

The Role of Preservation Solutions upon Saphenous Vein Endothelial Integrity and Function: Systematic Review and UK Practice Survey.

The long saphenous vein is the most used conduit in cardiac surgery, but its long-term patency is limited by vein graft disease (VGD). Endothelial dysfunction is a key driver of VGD; its aetiology is multi-factorial. However emerging evidence identifies vein conduit harvest technique and preservation fluids as causal in their onset and propagation. This study aims to comprehensively review published data on the relationship between preservation solutions, endothelial cell integrity and function, and VGD in human saphenous veins harvested for CABG. The review was registered with PROSPERO (CRD42022358828). Electronic searches of Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases were undertaken from inception until August 2022. Papers were evaluated in line with registered inclusion and exclusion criteria. Searches identified 13 prospective, controlled studies for inclusion in the analysis. All studies used saline as a control solution. Intervention solutions included heparinised whole blood and saline, DuraGraft, TiProtec, EuroCollins, University of Wisconsin (UoW), buffered, cardioplegic and Pyruvate solutions. Most studies demonstrated that normal saline appears to have negative effects on venous endothelium and the most effective preservation solutions identified in this review were TiProtec and DuraGraft. The most used preservation solutions in the UK are heparinised saline or autologous whole blood. There is substantial heterogeneity both in practice and reporting of trials evaluating vein graft preservation solutions, and the quality of existing evidence is low. There is an unmet need for high quality trials evaluating the potential for these interventions to improve long-term patency in venous bypass grafts.