Histidine-tryptophan-ketoglutarate Solution Research Articles

Mitigating Cold Ischemic Injury: HTK, UW and IGL-2 Solution's Role in Enhancing Antioxidant Defence and Reducing Inflammation in Steatotic Livers.

Liver transplantation remains the only definitive treatment for end-stage liver diseases. However, the increasing prevalence of fatty liver disease among potential donors exacerbates the shortage of suitable organs. This study evaluates the efficacy of the preservation solution Institut Georges Lopez-2 (IGL-2) compared to Histidine-Tryptophan-Ketoglutarate (HTK) and University of Wisconsin (UW) preservation solutions in mitigating ischemia-reperfusion injury (IRI) in steatotic livers. Using Zucker Obese rat livers, we assessed the impact of 24-h static cold storage (SCS) with each solution on transaminase release, glutathione redox balance, antioxidant enzyme activity, lipoperoxidation, and inflammation markers. IGL-2 and UW solutions demonstrated reduced transaminase and lactate levels compared to HTK, indicating better preservation of liver integrity. IGL-2 maintained a higher reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, suggesting more effective management of oxidative stress. Antioxidant enzyme activities catalase, superoxide dismutase, and glutathione peroxidase (CAT, SOD, GPX) were higher in IGL-2 preserved livers, contributing to decreased oxidative damage. Lipid peroxidation markers and inflammatory markers were lower in IGL-2 than in HTK, indicating reduced oxidative stress and inflammation. Additionally, improved mitochondrial function was observed in the IGL-2 group, correlating with reduced reactive oxygen species (ROS) production and lipid peroxidation. These findings suggest that IGL-2 offers superior preservation of liver viability, reduces oxidative stress, and minimizes inflammation compared to HTK and UW solutions. By maintaining a higher ratio of reduced glutathione and antioxidant enzyme activity, IGL-2 effectively mitigates the harmful effects of ischemia-reperfusion injury. The reduced lipid peroxidation and inflammation in the IGL-2 group further underscore its potential in improving liver transplant outcomes. These results highlight the importance of optimizing preservation solutions to enhance the viability and functionality of donor organs, potentially expanding the donor pool and improving the success rates of liver transplantation. Future research should focus on refining preservation techniques and exploring additional protective agents to further improve organ preservation and transplant outcomes.

Post-reperfusion syndrome among liver transplant recipients in HTK (Histidine- Tryptophan- Ketoglutarate) versus UW (University of Wisconsin) preservation solution

Post-reperfusion syndrome among liver transplant recipients in HTK (Histidine- Tryptophan- Ketoglutarate) versus UW (University of Wisconsin) preservation solution

N-terminal pro-B type natriuretic peptide as a predictor for myocardial preservation in cases of isolated severe Aortic stenosis

Background Myocardial hypertrophy is a common pathologic finding in the natural history of severe aortic stenosis. A hypertrophied myocardium predisposes the patient to decreased tolerance to ischemia and increased reperfusion injury, myocardial protection is of utmost importance in patients undergoing aortic valve replacement (AVR) for severe aortic valve stenosis. Myocardial protection techniques during cardiac arrest have been extensively investigated in the clinical setting of coronary revascularization. However, fewer studies have been carried out on patients affected by left ventricular (LV) hypertrophy, where the choice of type, and temperature of cardioplegia remains controversial. Aim The study investigates preoperative N-terminal pro-B type natriuretic peptide (NT pro-BNP), its relation to Troponin I levels, and whether it can predict a preferred cardioplegic solution by comparing the short-term outcomes of the two commonly used blood and Histidine-Tryptophan-Ketoglutarate (HTK) cardioplegic solutions in patients undergoing aortic valve replacement for severe aortic stenosis. Patients and methods A total of 72 patients will be randomly allocated into two groups; group (A=36) received HTK solution, and group (B=36) received blood cardioplegia. All anesthesia protocols are unified among all patients. All surgical procedures were conducted on a cardioplegic arrested heart via standard median sternotomy, utilizing full Cardiopulmonary bypass (CPB) via aorto-atrial cannulation and LV venting through a left atrial catheter under moderate hypothermia (28–32°C) by topical cooling. Results There was no statistically significant difference found between group A and group B regarding post-operative ejection fraction (EF) and newly developed postoperative Regional wall motion abnormalities (RWMA). There was no statistically significant difference found between group A and group B regarding the percentage of patients with atrial fibrillation, ventilation hours, and exploration while there was a statistically significant increase in troponin, I level in group B than group A. There was a statistically significant negative correlation between NT pro-BNP preoperative and aortic valve area (AVA) and also with ejection fraction preoperative while there was a statistically significant positive correlation found between NT pro-BNP and troponin I preoperative and postoperative. Conclusion HTK solution and Blood cardioplegia both offer sufficient protection for the myocardium. NT pro-BNP serves as a sensitive indicator for predicting the results and effectiveness of different cardioplegia types

Applicability of the histidine-tryptophan-ketoglutarate solution as a machine perfusion solution for marginal liver grafts.

There are very few reports comparing the use of the University of Wisconsin solution and histidine-tryptophan-ketoglutarate solution as machine perfusion solutions for marginal liver grafts. We aimed to clarify whether the use of the histidine-tryptophan-ketoglutarate solution in hypothermic machine perfusion improves the split-liver graft function in a large animal model. Porcine split-liver grafts were created by 75% liver resection. Hypothermic machine perfusion experimental groups were divided as follows: Group 1, perfusate, University of Wisconsin gluconate solution (UW group; n=5), and Group 2, perfusate, histidine-tryptophan-ketoglutarate solution (HTK group; n=4). After 4h of preservation, the liver function was evaluated using an isolated liver reperfusion model for 2h. In the HTK group, the portal vein and hepatic artery resistance during hypothermic machine perfusion and the portal vein resistance during isolated liver reperfusion were lower than those in the UW group. In addition, the total Suzuki score for hepatic ischemia-reperfusion injury in the HTK group was significantly better than that in the UW group. The number of anti-ETS-related genes staining-positive sinusoid epithelial cell nuclei in the HTK group was higher than that in the UW group (not significant). The histidine-tryptophan-ketoglutarate solution can be perfused with lower vascular resistance than the University of Wisconsin solution, reducing shear stress and preventing sinusoid epithelial cell injury in marginal grafts used as split-liver grafts.

Methane Admixture Protects Liver Mitochondria and Improves Graft Function after Static Cold Storage and Reperfusion

Mitochondria are targets of cold ischemia-reperfusion (IR), the major cause of cell damage during static cold preservation of liver allografts. The bioactivity of methane (CH4) has recently been recognized in various hypoxic and IR conditions as having influence on many aspects of mitochondrial biology. We therefore hypothesized that cold storage of liver grafts in CH4-enriched preservation solution can provide an increased defence against organ dysfunction in a preclinical rat model of liver transplantation. Livers were preserved for 24 h in cold histidine-tryptophan-ketoglutarate (HTK) or CH4-enriched HTK solution (HTK-CH4) (n = 24 each); then, viability parameters were monitored for 60 min during normothermic isolated reperfusion and perfusate and liver tissue were collected. The oxidative phosphorylation capacity and extramitochondrial Ca2+ movement were measured by high resolution respirometry. Oxygen and glucose consumption increased significantly while hepatocellular damage was decreased in the HTK-CH4 grafts compared to the HTK group. Mitochondrial oxidative phosphorylation capacity was more preserved (128.8 ± 31.5 pmol/s/mL vs 201.3 ± 54.8 pmol/s/mL) and a significantly higher Ca2+ flux was detected in HTK-CH4 storage (2.9 ± 0.1 mV/s) compared to HTK (2.3 ± 0.09 mV/s). These results demonstrate the direct effect of CH4 on hepatic mitochondrial function and extramitochondrial Ca2+ fluxes, which may have contributed to improved graft functions and a preserved histomorphology after cold IR.

S1229 The Feasibility and Safety of Selected Liver Grafts Flushed With Cold Normal Saline (NS) and Comparison With Liver Grafts Flushed With Histidine-Tryptophan-Ketoglutarate Solution in Living Donor Liver Transplantation

Introduction: Preservation solutions are required for organ viability in deceased donor liver transplantation (LT). However, their role in live donor LT (LDLT) has not been standardized. The aim of this study is to compare the outcomes of selected liver grafts flushed with cold normal saline (NS) with Histidine-Tryptophan-Ketoglutarate (HTK) solution. Methods: One hundred consecutive adult recipients who underwent right lobe LDLT from February 2020 to December 2020 at Gambat, Pakistan were studied. Recipients were assigned to receive “no preservation solution” (cases/non-HTK group; n=50) based on shorter CIT & no back Table reconstruction work or “HTK group” (controls; n=50) requiring standard back Table reconstruction. Various outcomes, including early graft dysfunction (bilirubin, transaminases, and INR), postoperative complications (biliary & vascular), hospital stay, and one-year survival, were compared between the two groups. The direct cost was also reported. Results: Demographics and clinical characters were comparable in the two groups. Comparing cases vs. controls, mean bilirubin, ALT, AST, and INR on the 7thpostoperative day were similar in the two groups. 5(10%) cases and 4(8%) controls developed EAD(p=0.72). Post-LT complications (biliary leak 2% in cases vs. 0 in control), strictures (12% in cases vs. 16% in controls), hepatic artery thrombosis (4% vs. 2%) and portal vein thrombosis (0 vs. 2%) were equally distributed. Mean hospital stay (11.02 + 2.63 and 12.06 + 3.68 days) and 30-day mortality (8% vs 8%) were also comparable in two groups. Finally, 1-year survival (92% vs 90%) based on Kaplan-Meier analysis was also comparable (p-value:0.71). The cost of using a non-HTK-based approach was much lesser than the HTK solution. (Figure) Conclusion: To our knowledge, this is the first innovative report on avoiding preservative solutions in LDLT recipients. We found that EAD including liver function tests; post-operative complications (biliary and vascular), 30 days’ mortality, and 1-year survival were comparable in the two groups. We also found that avoiding the preservative solution has an impact on saving direct costs. (Table). In our study, the postoperative complications and the overall one-year survival rate in the non-preservation group (92%) and the HTK group (90%) were equal and matched with other studies from the region. From an economic perspective, we also found that avoiding the use of preservation solutions is very attractive.Figure 1.: Kaplan-Meier showing a comparable survival rate in non-HTK and HTK groups at 1-year post-liver transplantation Table 1. - Recipient demographics, clinical characteristics, laboratory values, and complications in study groups Recipient demographics, clinical characteristics, laboratory values, and complications in study groups. Variables non-HTK group (n=50) HTK group (n=50) p-value Recipients Age(years) 39.18+11.69 36.84+6.77 0.224 Gender 44(88%) 46 (92%) 0.741 Male 6(12%) 4 (08%) Female BMI(kg/m2) 22.46±4.29 22.84±4.24 0.657 Etiology Viral 47 (94%) 45 (90%) NASH 2 (04%) 1 (02%) Alcoholic 00 (00%) 00 (00%) Budd Chiari 00 (00%) 1 (02%) PBC 00 (00%) 1 (02%) Wilson 1 (02%) 1 (02%) PSC 00 (00%) 1 (02%) HCC 11 (22%) 02 (04%) 0.015 Co-Morbidities DM 4 (08%) 2 (04%) 0.67 HTN 00 (00%) 3 (06%) 0.24 CVD 00 (00%) 00 (00%) 0.00 CTP score 0.59 A 3 (06%) 1 (02%) B 9 (18%) 9 (18%) C 38 (76%) 40 (80%) MELD-Na 19.53±5.51 20.88±4.75 0.19 Operation time (min) 537±70.66 534.60±60.72 0.85 Blood loss(ml) 1622±317.70 1512±300.775 0.07 Hospital stays(days) 11.02±2.63 12.06±3.68 0.10 Mean Post-operative labs (at day 07) Total bilirubin (mg/dL)INR (IU/L)ALT (IU/L)AST (IU/L) 2.96 ± 2.97 3.06 ± 3.24 0.91 1.44 ± 0.24 1.39 ± 0.18 0.82 186.79 ± 144.95 137.69 ± 97.28 0.05 119.69 ± 133.45 93.78 ± 85.65 0.26 Complication EAD 4 (8%) 5(10%) 0.727 PNF 00 1 (2%) 0.315 ACR 3(6%) 4 (8%) 0.695 HAT 2 (4%) 1(2%) 0.558 Sepsis 5 (10%) 4 (8%) 0.727 PVT 00 1 (2%) 0.315 Biliary complicationsStrictureLeak 6 (12%)1 (2%) 8 (16%)00 0.5640.315 Clavin-dindo Grade>III 11 (22%) 13 (26%) 0.64 30-day Mortality 4 (8%) 4 (8%) 1.00 1-year mortality (excluding 1st month) 00 1 (2%) 0.315 BMI: body mass index; HCC: hepatocellular carcinoma; HTN: hypertension; CVD: cardiovascular disease; CTP: Child Turcotte Pugh; INR: international normalized ratio; ALT: alanine aminotransferase; AST: aspartate aminotransferase; EAD: early graft dysfunction; PNF: primary non-function; ACR: acute cellular rejection; HAT: hepatic artery thrombosis; PVT: portal vein thrombosis.

P11.06: HTK vs WISCONSIN and Delayed Renal Graft Function

Introduction: Preservation solutions are beneficial for solid organ transplants, being an important factor in the development of delayed graft function (RFI), being associated with a reduction in graft survival after one year. Objectives: To compare the use of histidine-tryptophan-ketoglutarate (HTK) solution vs University of Wisconsin solution with the development of renal graft function delay (RFI). Material and Method: Observational (Cross Sectional), retrospective and analytical study. Renal transplant patients with cadaveric donors were included during the period between January 2017 and December 2021.T test was used for independent samples and Chi2 2x2 for categorical variables. An alpha value of ≤ 0.05 was determined for statistical significance. Results: 82 kidney transplant recipients were retrospectively compared with cadaveric, preserved HTK (n=49) and UW (n=33) donors. The mean age of the donors was 40 years. The incidence of RFI was 56%. In the Student test analysis, statistical significance was observed in donor age (37,31 vs 42,52 p=.035), donor BMI (25,78 vs 29,46p=.000), pre-ablation creatinine (0,94 vs 1,18 p=.014) and pre-ablation urea (28,86 vs 39,74 p=.006) and renal RFI. In the CHI2 analysis, the use of HTK solution (KANTRILEX/ CUSTOPLEX) was associated with 40.2% renal RFI development (p=.012) (OR 3.17 95% CI 1.26-7.95), compared to UW solution (14.6%) (p=.007) (OR 0.28 CI 95% 0.11-0.71). Conclusion: In our study, it was observed that the use of HTK solution was associated with a higher risk of renal RFI compared to UW solution.

Melatonin in preservation solutions prevents ischemic injury in rat kidneys.

Transplantation is lifesaving and the most effective treatment for end-stage organ failure. The transplantation success depends on the functional preservation of organs prior to transplantation. Currently, the University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) are the most commonly used preservation solutions. Despite intensive efforts, the functional preservation of solid organs prior to transplantation is limited to hours. In this study, we modified the UW solution containing components from both the UW and HTK solutions and analyzed their tissue-protective effect against ischemic injury. The composition of the UW solution was changed by reducing hydroxyethyl starch concentration and adding Histidine/Histidine-HCl which is the main component of HTK solution. Additionally, the preservation solutions were supplemented with melatonin and glucosamine. The protective effects of the preservation solutions were assessed by biochemical and microscopical analysis at 2, 10, 24, and 72 h after preserving the rat kidneys with static cold storage. Lactate dehydrogenase (LDH) activity in preservation solutions was measured at 2, 10, 24, and 72. It was not detectable at 2 h of preservation in all groups and 10 h of preservation in modified UW+melatonin (mUW-m) and modified UW+glucosamine (mUW-g) groups. At the 72nd hour, the lowest LDH activity (0.91 IU/g (0.63–1.17)) was measured in the mUW-m group. In comparison to the UW group, histopathological damage score was low in modified UW (mUW), mUW-m, and mUW-g groups at 10, 24, and 72 hours. The mUW-m solution at low temperature was an effective and suitable solution to protect renal tissue for up to 72 h.

Addition of oh8dG to Cardioplegia Attenuated Myocardial Oxidative Injury through the Inhibition of Sodium Bicarbonate Cotransporter Activity

The biomarker 8-hydroxy-2′-deoxyguanosine (oh8dG) is derived from oxidized nucleic acids or products of oxidant-mediated DNA damage. Enhanced sodium bicarbonate cotransporter (NBC) activity is caused by reactive oxygen species (ROS) production in ventricular myocytes. Thus, we hypothesized that cardioplegia-solution-mediated ROS generation may be involved in the regulation of NBC activity in cardiomyocytes and that oh8dG treatment may modulate ROS and associated NBC activity. Langendorff-free cardioplegia-arrested cardiac strips and cardiomyocytes were isolated to determine the NBC activity and effects of oh8dG on oxidative-stress-mediated cardiac damage markers. We first determined the histidine-tryptophan-ketoglutarate (HTK) solution mediated NBC activity in cardiac strips and cells. The oh8dG treatment attenuated NBC activity in the electroneutral or electrogenic form of NBC. Additionally, exposure to HTK solution induced ROS, whereas co-administration of oh8dG attenuated ROS-mediated NBC activity, reduced ROS levels, and decreased the expression of apoptotic markers and fibrosis-associated proteins in cardiac cells. The oh8dG-administrated cardiac tissues were also protected from enhanced HTK-induced damage markers, heat shock protein 60 and polyADP-ribose. Our results show that oh8dG has a protective role against myocardial oxidative damage and provides a useful treatment strategy for restoring cardiac function.

TJ-M2010-5 Attenuates Severe Myocardial Ischemia/Reperfusion Injury in Heart Transplantation by Inhibiting MyD88 Homodimerization In Vivo.

Survival of transplanted hearts is often limited by cold ischemia time. Here, we assessed the effects of the small molecular compound TJ-M2010-5 on graft preservation. In a cardiac cold ischemia/reperfusion model, TJ-M2010-5 ameliorated myocardial ischemia/reperfusion injury (MIRI) in histidine-tryptophan-ketoglutarate (HTK) organ preservation solution. When applied in HTK solution and on donors/recipients respectively, TJ-M2010-5 exerted optimal effects when applied as an additive in the HTK solution. TJ-M2010-5-administered mice exhibited shorter rebeating time; higher beating score; stronger and more regular sinus heart rate; and amelioration of apoptosis, inflammatory reactions, and myocardial injury. Mechanistically, TJ-M2010-5 inhibited the expression of key molecules in the toll-like receptor (TLR) signaling pathway and affected downstream proteins by inhibiting myeloid differentiation factor 88 homodimerization, thereby decreasing myocardial injury. Thus, TJ-M2010-5 may exert protective effects against MIRI by blocking the TLR signaling pathway. Our findings may lead to novel approaches for organ preservation, thereby reducing organ abandonment and improving recipient prognosis. The role of the TLR signaling pathway in MIRI progress and operation procedure of the MIRI model in vivo are presented in a graphical abstract (Online Abstract Figure).

Crystalloid Machine Perfusion with the Novel HTK-N Preservation Solution Reduces Microvascular Dysfunction in Circulatory Death Hearts

<h3>Purpose</h3> Microvascular dysfunction (MVD) in cardiac allografts is associated with allograft vasculopathy, graft failure, and death after heart transplantation. Prolonged ischemia and pronounced ischemia/reperfusion injury promote MVD. Circulatory death (CD) donor hearts are exposed to a warm ischemic period followed by machine (re)perfusion (MP) with warm blood. The novel histidine-tryptophane-ketoglutarate(HTK)-N solution has been developed to improve myocardial contractility and preserve the vascular viability of donor hearts. The impact of MP with hypothermic, oxygenated HTK-N solution on microvascular function has not been investigated yet. <h3>Methods</h3> In a pig model of CD, the microvascular function of hearts was either assessed for 60 min immediately after harvesting (CD-group) or hearts were maintained by MP with normothermic blood (CD-B group), hypothermic HTK (CD-HTK group), or HTK-N (CD-HTK-N group) solution for 4 h before microvascular evaluation (all N=5 per group). We measured microvascular blood flow (LDP) by a Laser-Doppler-Perfusion needle probe in the left ventricular (LV) wall in dependence of a balloon-induced LV-preload to evaluate the microvascular function. We analyzed the Immunoreactivity of intracellular (ICAM), vascular (VCAM), and platelet-endothelial (PECAM) cell adhesion molecules, as well as endothelial nitric oxide synthase (eNOS) of arterioles, and profiled the expression of 84 genes. We constructed gene expression networks using the Boruta machine learning algorithm for feature selection. <h3>Results</h3> Relative LDP (rLDP) was majorly improved by HTK-N perfusion (1.16±0.06) compared with the CD-group (0.96±0.07, p=0.142), CD-B- (0.86±0.07, p=0.016) and CD-HTK-group (0.92±0.04, p=0.065). After MP with HTK-N, the expression of endothelial viability marker eNOS majorly increased, and the expression of endothelial injury markers ICAM, VCAM, and PECAM majorly decreased. The groups CD and CD-B showed fragmented gene networks with heterogenous gene correlation. After HTK and HTK-N perfusion, groups showed centralized networks with homogenous correlation and majorly reconstituted cluster regions. <h3>Conclusion</h3> MP with HTK-N counteracts MVD, preserves the microvascular endothelium, and reduces the expression of cell adhesion molecules in the coronary microvasculature of CD-hearts.

Current Trends in Organ Preservation Solutions for Pancreas Transplantation: A Single-Center Retrospective Study.

Due to the high vulnerability of the pancreas to ischemia-reperfusion injury, choices regarding preservation solution markedly affect pancreas transplant success. A retrospective single-center analysis of 380 pancreas transplants (2000-2019) was performed to correlate current preservation solutions with transplant outcomes. Early graft failure requiring transplantectomy within 30days post-transplant occurred in 7.5% for University of Wisconsin (UW) group (n = 267), 10.8% of Celsior (CS) group (n = 83), 28.5% of Histidine-Tryptophan-Ketoglutarate (HTK) group (n = 7), and none for Institut Georges Lopez-1 (IGL-1) group (n = 23). The most common causes of technical failures in this cohort included abdominal hemorrhage (8.4%); graft pancreatitis (3.7%); fluid collections (2.6%); intestinal complications (6.6%); and vascular thrombosis (20.5%). Although IGL-1 solution provided lower surgical complication rates, no significant differences were found between studied groups. Nevertheless, HTK solution was associated with elevated pancreatitis rates. The best graft survival was achieved at 1year using UW and IGL-1, and at 3 and 5years using IGL-1 (p = 0.017). There were no significant differences in patient survival after a median follow-up of 118.4 months. In this setting therefore, IGL-1 solution appears promising for perfusion and organ preservation in clinical pancreas transplantation, compared to other commonly used solutions.

Bretschneider Solution and Two Antianginal Drugs Protect Peripheral Tissue in an Animal Model of Hemorrhagic Shock.

Shock and subsequent resuscitation provoke ischemia-reperfusion injury. Trimetazidine (TMZ), allopurinol (ALO), and histidine-tryptophan-ketoglutarate (HTK) solution, can protect from ischemia-reperfusion injury in chronic coronary syndromes and in transplantation. The objective of the current study is to compare, in a hemorrhagic shock and standard resuscitation animal model, organ damage parameters between placebo and treatment with TMZ, ALO, or HTK. Shock was induced in Wistar rats by controlled arterial bleeding, maintaining mean arterial pressure between 38 and 42 mm Hg for 60 minutes; then, drawn blood was reinfused. Animals were divided into: Sham (n = 4), Control (n = 6), TMZ (n = 7), ALO (n = 9), and HTK (n = 7). At the end of the experiment, animals were sacrificed and tissue harvested. TMZ, ALO and HTK decreased histopathologic damage in heart [Control: 1.72 (1.7-1.77); TMZ: 1.75 (1.72-1.79); ALO: 1.75 (1.74-1.8); HTK: 1.82 (1.78-1.85); all P < 0.05], kidney [Control: 3 (2-3); TMZ: 1 (1-2); ALO: 1 (1-1); HTK: 1(1-1); all P < 0.05] and intestine [Control: 3 (2-3); TMZ: 1 (1-2); ALO: 1 (1-1); HTK: 1 (0-2); all P < 0.05]. Also, treatment with TMZ, ALO, and HTK increased immunohistochemical expression of thioredoxin-1 in heart [Control: 6.6 (5.6-7.4); TMZ: 9.5 (8.1-9.7); ALO: 9.1 (8.4-10.2); HTK: 14.2 (12.6-15); all P < 0.05]; and kidney [Control: 4.6 (4-5.1); TMZ: 9.7 (9.3-9.9); ALO: 9.6 (9-9.9); HTK: 16.7 (16.1-17); all P < 0.05]. In an experimental model of hemorrhagic shock, TMZ, ALO, and HTK solution attenuated cell damage in multiple parenchyma and increased antioxidant defenses.

Impact of graft weight change during perfusion on hepatocellular carcinoma recurrence after living donor liver transplantation

Inadequate liver volume and weight is a major source of morbidity and mortality after adult living donor liver transplantation (LDLT). The purpose of our study was to investigate HCC recurrence, graft failure, and patient survival according to change in right liver graft weight after histidine-tryptophan-ketoglutarate (HTK) solution perfusion in LDLT. Two hundred twenty-eight patients underwent LDLT between 2013 and 2017. We calculated the change in graft weight by subtracting pre-perfusion graft weight from post-perfusion graft weight. Patients with increased graft weight were defined as the positive group, and patients with decreased graft weight were defined as the negative group. After excluding patients who did not meet study criteria, 148 patients underwent right or extended right hepatectomy. The negative group included 89 patients (60.1%), and the positive group included 59 patients (39.9%). Median graft weight change was -28 g (range, -132-0 g) in the negative group and 21 g (range, 1-63 g) in the positive group (p < 0.001). Median hospitalization time was longer for the positive group than the negative group (27 days vs. 23 days; p = 0.048). There were no statistical differences in tumor characteristics, postoperative complications, early allograft dysfunction, or acute rejection between the two groups. Disease-free survival, death-censored graft survival, and patient survival were lower in the positive group than the negative group. Additionally, the positive group showed strong association with HCC recurrence, death-censored graft survival, and patient survival in multivariate analysis. This study suggests that positive graft weight change during HTK solution perfusion indicates poor prognosis in LDLT.

Impact of Histidine-Tryptophan-Ketoglutarate Preservation Solution in Heart Transplantation with Extended Distance

<h3>Purpose</h3> In countries with such continental dimensions, and low organ donation rates and recovery, strategies to shorten the waiting time in heart transplantation (HT) list are still required. A prolonged ischemic time (pISQT, >240 min) has been reported to be a significant factor leading to primary graft dysfunction (PGD). Thus, optimal heart preservation is mandatory for transplant procedures with pISQT. Use of Histidine-Tryptophan-Ketoglutarate (HTK) solution has been suggested to improve extended organ preservations up to 180 min. This study investigated the impact of the donor distance (DD) from transplantation center and pISQT on PGD after HT using preservation with HTK solution. <h3>Methods</h3> Between January 2017 and December 2018, all 92 consecutive patients underwent HT at our institution after preservation with HTK solution were retrospectively evaluated divided into 2 groups according to the DD: (G1) 46 patients underwent HT with a DD <100km, and (G2) 46 patients after HT with a DD >100km. No significant differences were observed with regard to gender, age, diagnosis, donor inotropic support, and donor-recipient weight ratio among patients in G2 when compared with G1. The PGD was characterized using the ISHLT defined criteria. Descriptive analyses of the results are presented as mean values and standard deviations. The analytical studies were performed with the Fisher exact test. Kaplan-Meier and log-rank tests were performed to investigate survivals. All analyses were performed using R and p<0.05 was considered to be significant. <h3>Results</h3> The incidence of PGD was similar in both groups (p=0.81). After risk adjustment, longer DD were associated with a significantly lower risk of mortality at both 60 days (p=0.05, Figure 1). <h3>Conclusion</h3> This study illustrates that HTK solution may help to expand donor acceptance criteria to include more distant donor heart locations and accepting longer allograft ischemic times without increase in PGD and mortality after transplantation.

Impact of Graft Weight Change During Perfusion on Hepatocellular Carcinoma Recurrence After Living Donor Liver Transplantation.

BackgroundsInadequate liver volume and weight is a major source of morbidity and mortality after adult living donor liver transplantation (LDLT). The purpose of our study was to investigate HCC recurrence, graft failure, and patient survival according to change in right liver graft weight after histidine-tryptophan-ketoglutarate (HTK) solution perfusion in LDLT.MethodsTwo hundred twenty-eight patients underwent LDLT between 2013 and 2017. We calculated the change in graft weight by subtracting pre-perfusion graft weight from post-perfusion graft weight. Patients with increased graft weight were defined as the positive group, and patients with decreased graft weight were defined as the negative group.ResultsAfter excluding patients who did not meet study criteria, 148 patients underwent right or extended right hepatectomy. The negative group included 89 patients (60.1%), and the positive group included 59 patients (39.9%). Median graft weight change was -28 g (range; -132–0 g) in the negative group and 21 g (range; 1–63 g) in the positive group (P<0.001). Median hospitalization time was longer for the positive group than the negative group (27 days vs. 23 days; P=0.048). There were no statistical differences in tumor characteristics, postoperative complications, early allograft dysfunction, or acute rejection between the two groups. Disease-free survival, death-censored graft survival, and patient survival were lower in the positive group than the negative group. Additionally, the positive group showed strong association with HCC recurrence, death-censored graft survival, and patient survival in multivariate analysis.ConclusionThis study suggests that positive graft weight change during HTK solution perfusion indicates poor prognosis in LDLT.

Efficacy of Histidine-Tryptophan-Ketoglutarate Solution Versus Blood Cardioplegia in Cardiac Surgical Procedures: A Randomized Controlled | Parallel Group Study.

In cardiac surgery, myocardial protection is required during cross-clamping followed by reperfusion. The use of cardioplegic solutions helps preserve myocardial energy stores, hindering electrolyte disturbances and acidosis during periods of myocardial ischaemia. This study aimed to compare the efficacy and safety between the histidine-tryptophan-ketoglutarate (HTK) solution and blood cardioplegia in various cardiac surgeries. Three-hundred-twenty patients aged 30-70 years old undergoing various cardiac surgeries were randomized into the HTK group and the blood cardioplegia group. The ventilation time, total bypass time, cross-clamp time, length of intensive care unit (ICU) or hospital stay, and postoperative complications were analyzed. The total bypass time and cross-clamp time were significantly shorter in the HTK group than in the blood cardioplegia group (P < 0.001). Segmental wall motion abnormalities (SWMA) at postoperative echocardiography were significantly higher in in the blood cardioplegia group (P = 0.008). The number of patients requiring DC Shock was significantly higher in the HTK group (P < 0.001). The number of patients requiring inotropic support was significantly higher in the blood cardioplegia group (P < 0.001). The length of ICU, hospital stay, and ventilation time were significantly longer in the blood cardioplegia group than in the HTK group (P = 0.004, P < 0.001, P < 0.001, respectively). The number of patients requiring prolonged ventilation was significantly higher in the blood cardioplegia group compared with the HTK group (P = 0.022). There was no significant difference between the study groups regarding electrocardiographic changes, 30-day mortality, and 30-day readmission. The use of HTK cardioplegia was associated with significantly shorter cross-clamp time, bypass time, duration of mechanical ventilation, length of ICU stay, and length of hospital stay. It is associated with less incidence of postoperative segmental wall abnormalities and less need for inotropic support than blood cardioplegia. Custodiol cardioplegia is a safe and feasible option that can be used as an effective substitute for blood cardioplegia to enhance myocardial protection.

Comparison of histidine-tryptophan-ketoglutarate solution versus ringer lactate as perfusion fluid in live donor renal transplant - A randomised controlled trial

Objective: Ringer's lactate (RL) was one of the perfusion fluid used in renal transplants, which were replaced by perfusion fluid with an intracellular composition like histidine-tryptophan-ketoglutarate (HTK) solution. These are preferred in cadaveric renal transplants. However, there are no guidelines for live-related donor renal transplant. We study whether HTK solution is better than RL solution, an extracellular composition fluid in preserving allograft in live-related donor renal transplantation. Materials and Methods: A single-blinded randomized trial comparing HTK solution and RL solution in 80 patients undergoing live-related donor renal transplantation from July 2017 to June 2018. The outcome was measured in serum cystatin C and plasma malondialdehyde (MDA) and serum creatinine for 30 days. Results: In 19 cases, surgeons preferred HTK solution as perfusion fluid due to the presence of multiple arteries; hence, these cases are removed from analysis due to deviation from the study protocol. Four patients in the HTK group and five patients in the RL group were excluded due to loss to follow-up. Recipient age, sex, and donor age, sex, and basic disease were comparable in both groups. The higher warm ischemia in the HTK group (5.58 min [standard deviation (SD) 1.44 min]) as compared to the RL group (5.00 min [SD 1.12 min]) with P 0.096. Similarly, the longer cold ischemia in the HTK group (82.00 min [SD 21.31 min]) as compared to the RL group (70.32 min [SD 24.56 min]) with P 0.783. 8.3% rejection in the HTK group and 17.9% rejection in the RL group. Serum cystatin C, marker of glomerular filtration was comparable, HTK group ((3.75 ± 1.98 mg/l) and RL (3.94 ± 1.68 mg/l) with P 0.714. The plasma MDA marker of ischemia-reperfusion injury was also comparable HTK group (80.16 ± 80.08 ng/ml) and RL group (61.50 ± 92.23 ng/ml) with a P 0.446. Fall in serum creatinine was significantly more in the HTK group than RL. At the end of 30 days, both groups had similar levels of serum creatinine level. Conclusion: Graft perfused by HTK solution and RL solution at our center had comparable 30-day outcomes. Although none of the differences was statistically significant, the HTK group had consistently better metrics in terms of fall in creatinine and serum cystatin C despite a trend to longer ischemia times and higher plasma MDA levels.

Custodiol versus extracellular crystalloid cardioplegia in mitral valve replacement in patients with low ejection fraction

Background The use of cardioplegia solution is aimed to avoid myocardial muscle damage, leading to poor contraction and abnormal increased release of cardiac biomarkers enzymes during cardiac arrest. It remains the primary method for myocardial protection against ischemia–reperfusion injury during cardiac surgery. Cardioplegia was first presented as an agent for hypothermic hyperkalemic arrest. Blood was then introduced as a vehicle to convey potassium to the heart. Histidine–tryptophan–ketoglutarate solution is safe and used as a single dose that can last for up to 3 h. Comparison between custodiol cardioplegia and cold blood cardioplegia still remains a big debate till now. Objective To compare the clinical outcomes of custodiol solution with cold blood cardioplegia in mitral valve replacement (MVR) with cardiac ejection fraction less than 45%. Patients and methods This single‑center randomized prospective study was carried out from January 2018 till June 2019 at Ain Shams University hospitals. Overall, 65 patients with poor left ventricular function undergoing mitral valve replacement were divided randomly according to type of myocardial protection into two groups: group A included 30 patients who received custodiol cardioplegia, and group B included 35 patients who received cold blood cardioplegia. Data from each group were collected and compared with each other. Results Baseline demographic and intraoperative data showed no significant difference between the two groups. The need for inotropic support, length of mechanical ventilation, and ICU stay were statistically nonsignificant between the two groups. There was a statistically significant difference regarding the rhythm upon declamping [ventricular fibrillation (VF) in 17 (56.7%) cases in group A and nine (25.7%) cases in group B (P=0.016)], and also there was a significant difference in times of defibrillation cardioversion (DC) shock given after declamping (P=0.005). Overall mortality shows a statistically nonsignificant difference. There is a significant difference in postoperative echo assessment for both groups [ejection fraction in group A: 53.17±7.73 compared with 49.06±7.170 in group B (P=0.031)], and there is also a difference in hemoglobin postoperatively, with 10.35±0.843 in group A compared with 10.88±0.798 in group B (P=0.013). Conclusion Cardiac arrest using custodiol cardioplegia is a good choice in mitral valve replacement with the advantage of giving only one dose of cardioplegia without interruption of the operation, and also it gives good postoperative echo results than cold blood cardioplegia. Its disadvantages are lower hemoglobin levels postoperatively and hyponatremia during bypass in comparison with cold blood cardioplegia.

Histidine-tryptophan-ketoglutarate solution versus University of Wisconsin solution in adult-to-adult living donor liver transplantation: A propensity score matching analysis from mainland China.

To compare the difference between University of Wisconsin (UW) solution and histidine-tryptophan-ketoglutarate (HTK) solution in adult living donor liver transplantation (LDLT).This study included LDLT patients at the Liver Transplantation Center of West China Hospital of Sichuan University from November 2001 to June 2018. These patients were classified into 2 groups depending on the use of the different preservation solutions, and the confounding factors between the 2 groups were eliminated by propensity score matching. Finally, the incidence of complications; serum examination at postoperative days 1, 3, 5, 7, 14, 21, and 30; and the overall survival rate of the 2 groups were compared to observe whether there were any differences between the 2 preservation solutions.Of the 298 patients we screened, 170 were treated with UW solution and 128 with HTK solution. After propensity score matching, 106 pairs of patients were selected. In the comparison of the 2 groups, the length of intensive care unit stay in the UW group was significantly longer than that in the HTK group (P = .022), but there was no difference in the total length of hospital stay between the 2 groups (P = .277). No statistically significant difference was observed in the 2 groups in terms of the incidence of complications or postoperative examinations. However, the incidence of early allograft dysfunction in the HTK group was slightly lower than that in the UW group (HTK: UW = 14.1%: 20.7%), although the difference was not statistically significant. In terms of the overall survival rate, the 1, 3, and 5-year survival rates of the HTK group were 85.5%, 70.2%, and 65.1%, respectively, while the 1, 3, and 5-year survival rates of the UW group were 83.1%, 67.2%, and 59.8%, respectively, and there was no significant difference between the 2 groups.In conclusion, our study shows that UW solution and HTK solution are equivalent in perioperative safety, the recovery of transplanted liver function, the occurrence of postoperative complications and overall survival and can be safely and effectively applied in adult LDLT. If economic factors are taken into account, HTK can save costs to a certain extent.