Histidine-tryptophan-ketoglutarate Research Articles

Transcriptomic Changes in the Myocardium and Coronary Artery of Donation after Circulatory Death Hearts following Ex Vivo Machine Perfusion.

Donation after circulatory death (DCD) hearts are predominantly maintained by normothermic blood perfusion (NBP). Nevertheless, it was shown that hypothermic crystalloid perfusion (HCP) is superior to blood perfusion to recondition left ventricular (LV) contractility. However, transcriptomic changes in the myocardium and coronary artery in DCD hearts after HCP and NBP have not been investigated yet. In a pig model, DCD hearts were harvested and maintained for 4 h by NBP (DCD-BP group, N = 8) or HCP with oxygenated histidine-tryptophane-ketoglutarate (HTK) solution (DCD-HTK, N = 8) followed by reperfusion with fresh blood for 2 h. In the DCD group (N = 8), hearts underwent reperfusion immediately after procurement. In the control group (N = 7), no circulatory death was induced. We performed transcriptomics from LV myocardial and left anterior descending (LAD) samples using microarrays (25,470 genes). We applied the Boruta algorithm for variable selection to identify relevant genes. In the DCD-BP group, compared to DCD, six genes were regulated in the myocardium and 1915 genes were regulated in the LAD. In the DCD-HTK group, 259 genes were downregulated in the myocardium and 27 in the LAD; and 52 genes were upregulated in the myocardium and 765 in the LAD, compared to the DCD group. We identified seven genes of relevance for group identification: ITPRIP, G3BP1, ARRDC3, XPO6, NOP2, SPTSSA, and IL-6. NBP resulted in the upregulation of genes involved in mitochondrial calcium accumulation and ROS production, the reduction in microvascular endothelial sprouting, and inflammation. HCP resulted in the downregulation of genes involved in NF-κB-, STAT3-, and SASP-activation and inflammation.

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

Efficacy and short-term outcomes of myocardial protection using single-dose histidine-tryptophan-ketoglutarate cardioplegia during aortic root surgery with different duration of myocardial ischemia

Objective: To explore the efficacy of myocardial protection with single-dose histidine-tryptophan-ketoglutarate (HTK) cardioplegia during aortic root operation, and the correlation between short-term clinical outcomes and duration of myocardial ischemia. Methods: The data of clinical cases undergoing myocardial protection with single-dose HTK cardioplegia during aortic root operation from January 2018 to December 2022 were retrospectively reviewed. Patients were divided into conventional HTK cardioplegia group (<3 h) and prolonged HTK cardioplegia group (≥3 h) according to duration of intraoperative myocardial ischemia. A 1∶1 propensity score matching was performed and the correlations between duration of myocardial ischemia and postoperative short-term outcomes (30-day mortality, readmission, mechanical circulation support and renal insufficiency) were analyzed. Results: A total of 282 patients were included in the final analysis, with 210 cases in the conventional HTK cardioplegia group and 72 cases inthe prolonged HTK cardioplegia group before matching. After matching, there were 64 cases (53 males and 11 females) in the conventional HTK cardioplegia group, with a mean age of (49.4±14.2) years. The prolonged HTK cardioplegia group had 64 cases (55 males and 9 females), with a mean age of (50.5±12.3) years. Higher sensitivity troponin [12 h: 10.1 (4.6, 18.7) μg/Lvs 4.1(2.2, 8.6) μg/L, P=0.002; 24 h: 7.7 (4.5, 19.0) μg/L vs 4.8 (2.2, 11.9) μg/L, P=0.025] and creatine kinase isoenzyme[12 h: 46.3 (28.1, 62.4) μg/L vs 20.7(14.1, 32.9) μg/L, P<0.001; 24 h: 26.3(13.4, 49.2) μg/L vs 14.5 (10.1, 33.5)μg/L, P=0.011] after surgery was detected in prolonged HTK cardioplegia group. Comparisons of other primary and secondary endpoint events showed no significant differences between the two groups (all P>0.05). Multivariate binary logistic regression showed that duration of myocardial ischemia had no significant effect on postoperative 30-day mortality (OR=1.255, 95%CI: 0.500-3.148, P=0.629), 30-day readmission (OR=0.378, 95%CI: 0.069-2.065, P=0.261) and mechanical circulation support (OR=0.991, 95%CI: 0.331-2.970, P=0.998). Conclusion: During aortic root surgery, single-dose HTK cardioplegia may provide satisfactory myocardial protection, and there was no significant correlation between duration of myocardial ischemia and short-term clinical outcomes.

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

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. 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. 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). 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.

Del Nido cardioplegia or potassium induces Nrf2 and protects cardiomyocytes against oxidative stress.

Open heart surgery is often an unavoidable procedure for the treatment of coronary artery disease. The procedure-associated reperfusion injury affects postoperative cardiac performance and long-term outcomes. We addressed here whether cardioplegia essential for cardiopulmonary bypass surgery activates Nrf2, a transcription factor regulating the expression of antioxidant and detoxification genes. With commonly used cardioplegic solutions, high K+, low K+, Del Nido (DN), histidine-tryptophan-ketoglutarate (HTK), and Celsior (CS), we found that DN caused a significant increase of Nrf2 protein in AC16 human cardiomyocytes. Tracing the ingredients in DN led to the discovery of KCl at the concentration of 20-60 mM capable of significant Nrf2 protein induction. The antioxidant response element (ARE) luciferase reporter assays confirmed Nrf2 activation by DN or KCl. Transcriptomic profiling using RNA-seq revealed that oxidation-reduction as a main gene ontology group affected by KCl. KCl indeed elevated the expression of classical Nrf2 downstream targets, including TXNRD1, AKR1C, AKR1B1, SRXN1, and G6PD. DN or KCl-induced Nrf2 elevation is Ca2+ concentration dependent. We found that KCl decreased Nrf2 protein ubiquitination and extended the half-life of Nrf2 from 17.8 to 25.1 mins. Knocking out Keap1 blocked Nrf2 induction by K+. Nrf2 induction by DN or KCl correlates with the protection against reactive oxygen species generation or loss of viability by H2O2 treatment. Our data support that high K+ concentration in DN cardioplegic solution can induce Nrf2 protein and protect cardiomyocytes against oxidative damage.NEW & NOTEWORTHY Open heart surgery is often an unavoidable procedure for the treatment of coronary artery disease. The procedure-associated reperfusion injury affects postoperative cardiac performance and long-term outcomes. We report here that Del Nido cardioplegic solution or potassium is an effective inducer of Nrf2 transcription factor, which controls the antioxidant and detoxification response. This indicates that Del Nido solution is not only essential for open heart surgery but also exhibits cardiac protective activity.

A propensity score matched analysis of liver transplantation outcomes in the setting of preservation solution shortage

The recent shortage of the University of Wisconsin (UW) solution prompted increased utilization of histidine-tryptophan-ketoglutarate (HTK) solution for liver graft preservation. This contemporary study analyzed deceased donor liver transplant outcomes following preservation with HTK vs UW. Patients receiving deceased donor liver transplantations between January 1, 2019, and June 30, 2022, were retrospectively identified utilizing the Organ Procurement and Transplant Network database, stratified by preservation with HTK vs UW, and a propensity score matching analysis was performed. Outcomes assessed included rates of primary nonfunction, graft survival, and patient survival. There were 4447 patients in each cohort. Primary nonfunction occurred in 60 (1.35%) patients in the HTK group vs 25 (0.54%) in the UW group (P < .001). HTK was associated with lower 90-day graft survival (94.39% vs 96.09%; P < .001) and 90-day patient survival (95.97% vs 97.38%; P = .001). Unmatched donation after cardiac death-specific analysis of HTK vs UW demonstrated respective rates of primary nonfunction of 1.63% vs 0.82% (P = .20), 90-day graft survival of 92.50% vs 95.29% (P = .069), and 90-day patient survival of 93.90% vs 96.35% (P = .077). These results suggest that HTK may not be an equivalent preservation solution for deceased donor liver transplantation.

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

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

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. 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. 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. 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.

Protective Effects of Different Hypothermal Preservation Solutions on Structure and Function of Isolated Rat Arteries.

With the increasing application of vascular reconstruction in surgical procedures, allogeneic vessels are becoming more popular in clinical practice due to their abundant sources, precise diameter matching, improved histocompatibility, and higher long-term patency rate. This study aimed to investigate the protective effect of various preservation solutions on the function and structure of the isolated rat abdominal aorta preserved under hypothermal conditions. The study utilized a total of 150 Sprague-Dawley (SD) rats, with 144 rats allocated to the experimental groups and 6 rats allocated to the control groups. The abdominal aorta of the rats was chosen as the subject of our research. The aorta in the experimental groups were randomly assigned to 4 groups: University of Wisconsin (UW) solution group, histidine-tryptophan-ketoglutarate (HTK) solution group, normal saline (NS) group, and sodium lactate Ringer's solution (RS) group. Samples were subjected to examination after preservation periods of 1 day, 3 days, 5 days, 7 days, 14 days, 30 days, and 90 days. Evaluation of vascular physiological function involved detecting and assessing vasoconstriction ability and measuring cell viability through the MTT test. Evaluation of the vascular wall structure involved tension tolerance tests and pathological staining. The pathogen-positive rate in the HTK group and NS group at 1 month was 16.7%. Regarding the vascular skeleton structure, both the UW group and HTK group exhibited intact structures after 2 weeks of preservation, with slightly edematous collagen and elastic fibers, which was significantly better than that of the NS group and RS group. In terms of cell activity and contractile function, all preservation groups showed similar effects within 2 weeks. However, after 2 weeks, the UW group showed the most favorable preservation effect (P<0.05). In terms of vascular tension, different groups exhibited similar effects within 1 week. However, after 2 weeks, the UW group showed the best preservation effect (P<0.05). All 4 types of preservation solution had a preservation effect on the structure and function of isolated blood vessels during short-term hypothermal preservation. However, after 2-week preservation, the UW solution was found to be the most suitable solution for the preservation of blood vessels.

Postoperative sodium concentrations after cardiac surgery using histidine- tryptophan-ketoglutarate cardioplegia and cardiopulmonary bypass – a retrospective study

Introduction: Histidine-tryptophan-ketoglutarate (HTK) cardioplegia is used to induce cardiac arrest during cardiopulmonary bypass (CPB) in cardiac surgery. HTK cardioplegia is hyponatremic (15 mmol/L) and slightly hyperosmolar (310 mOsm/kg) and can induce hyponatremia when it enters systemic circulation. The purpose of this study is to investigate the effect of HTK cardioplegia, cannulation strategy and intraoperative correction of sodium levels on postoperative sodium concentration. Secondly, the effect of the sodium concentrations on postoperative agitation is evaluated. Methods: Patients who underwent cardiac surgery using CPB and HTK cardioplegia were included in this retrospective study. Sodium concentrations of arterial blood gases (ABG) and laboratory blood samples were analyzed at multiple points in time. It was recorded if the perfusionist corrected intraoperative hyponatremia with hypertonic saline or sodium bicarbonate 8.4%. Characteristics of the patients, intraoperative data and the patient’s Richmond Agitation-Sedation Scale (RASS) score were collected. Results: The median sodium concentration on ABG [IQR] decreased from 139 mmol/L [138-140] to 125.5 mmol/L [122-130] (p &lt; 0.001) after the administration of HTK cardioplegia. The median sodium concentration after the administration of HTK cardioplegia was significantly lower in the group with single cannulation than with double cannulation (123 mmol/L [121-125] vs. 130 mmol/L [128-133]; p&lt;0.001). The median sodium concentration increased to 134 mmol/L [133-136] (p=0.007) at T6. There was no significant difference in postoperative sodium concentration between patients who received correction intraoperatively and those who did not, or between patients who had agitation and those who had not. Conclusions: The administration of HTK cardioplegia induced acute hyponatremia during cardiac surgery mainly in patients with single venous cannulation. Postoperatively, a normalization of sodium concentrations can be observed. No difference in postoperative sodium concentration was observed with or without intraoperative correction of sodium. Intraoperative correction of hyponatremia shows no benefit or harm on postoperative sodium concentrations. Hyponatremia could be avoided or at least diminished by using double venous cannulation.

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.

Hyperkalemic or Low Potassium Cardioplegia Protects against Reduction of Energy Metabolism by Oxidative Stress.

Open-heart surgery is often an unavoidable option for the treatment of cardiovascular disease and prevention of cardiomyopathy. Cardiopulmonary bypass surgery requires manipulating cardiac contractile function via the perfusion of a cardioplegic solution. Procedure-associated ischemia and reperfusion (I/R) injury, a major source of oxidative stress, affects postoperative cardiac performance and long-term outcomes. Using large-scale liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolomics, we addressed whether cardioplegic solutions affect the baseline cellular metabolism and prevent metabolic reprogramming by oxidative stress. AC16 cardiomyocytes in culture were treated with commonly used cardioplegic solutions, High K+ (HK), Low K+ (LK), Del Nido (DN), histidine-tryptophan-ketoglutarate (HTK), or Celsior (CS). The overall metabolic profile shown by the principal component analysis (PCA) and heatmap revealed that HK or LK had a minimal impact on the baseline 78 metabolites, whereas HTK or CS significantly repressed the levels of multiple amino acids and sugars. H2O2-induced sublethal mild oxidative stress causes decreases in NAD, nicotinamide, or acetylcarnitine, but increases in glucose derivatives, including glucose 6-P, glucose 1-P, fructose, mannose, and mannose 6-P. Additional increases include metabolites of the pentose phosphate pathway, D-ribose-5-P, L-arabitol, adonitol, and xylitol. Pretreatment with HK or LK cardioplegic solution prevented most metabolic changes and increases of reactive oxygen species (ROS) elicited by H2O2. Our data indicate that HK and LK cardioplegic solutions preserve baseline metabolism and protect against metabolic reprogramming by oxidative stress.

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.

Murine and Human Gastric Tissue Establishes Organoids after 48 Hours of Cold Ischemia Time during Shipment.

An inadequate supply of fresh tissue is a major limitation of three-dimensional patient-derived gastric organoid research. We propose that tissue procurement for organoid culture could be increased by developing a cold storage shipment protocol for fresh surgical tissues. Sixty stomach specimens from C57BL/6J mice were resected, of which forty-five were stored in Hank's Balanced Salt (HBSS), University of Wisconsin (UW), or Histidine-Tryptophan-Ketoglutarate (HTK) solutions for subsequent organoid culture. Stomachs were dissociated and processed into gastric organoids as fresh tissue or after transport at 4 °C for 24 or 48 h. All gastric organoid cultures were established and maintained for 10 passages. Cold storage for 24 or 48 h did not significantly affect organoid viability. Although cold storage was associated with decreased organoid growth rate, there were no differences in viability, cytotoxic dose response, or LGR5 and TROY stem cell gene expression compared to organoids prepared from fresh tissue. As a proof of concept, six human gastric cancer organoids were established after 24 or 48 h of storage. Patient-derived gastric organoids from mouse and human gastric tissue can be established after 48 h of cold ischemia. Our method, which only requires ice packs, standard shipping containers, and HBSS is feasible and reliable. This method does not affect the reliability of downstream dose-response assays and maintains organoid viability for at least 10 passages. The shipment of fresh tissue for organoid procurement could serve to enhance multicenter collaboration and achieve more elaborate or controlled organoid experimentation.

Comparison of Single-Dose Cardioplegia in Valvular Heart Surgery: Lactated Ringer's-Based del Nido vs. Histidine-Tryptophan-Ketoglutarate Cardioplegia Solution.

This study evaluated myocardial protection and clinical outcomes when using lactated Ringer's solution as the base solution for del Nido cardioplegia compared with histidine-tryptophan-ketoglutarate (HTK) solution in valvular surgery. From January 2017 to May 2018, 71 adult patients who underwent valvular surgery with del Nido cardioplegia (n=37) or HTK cardioplegia (n=34) were retrospectively analyzed. Patients' characteristics were comparable between groups. Postoperative peak troponin T levels were similar. The del Nido group had a decreased incidence of ventricular fibrillation after aortic cross-clamp removal (13.51 vs. 55.88%; P<0.001), lower total volume of cardioplegia administered (1,000 [1,000, 1,250] vs. 1,800 [1,500, 2,000] mL; P<0.001), shorter hospital stay (6 [5, 8] vs. 7 [6, 10] days; P=0.03), and less postoperative red cell transfusion (34.29 vs. 61.11%; P=0.024). There is no difference in aortic cross-clamping time, postoperative change in left ventricular ejection fraction, intensive care unit stay, duration of inotropic support, new onset of atrial fibrillation, in-hospital mortality, complications, and three-year overall survival rate. Lactated Ringer's-based del Nido cardioplegia can be safely used for valvular surgery with acceptable clinical outcomes compared to HTK cardioplegia.

Comparison of Bretschneider’s Histidine–tryptophan–ketoglutarate Cardioplegia Solution and Conventional Blood Cardioplegia Solution in Terms of Postoperative Acute Kidney Injury and Outcome Parameters

Comparison of Bretschneider’s Histidine–tryptophan–ketoglutarate Cardioplegia Solution and Conventional Blood Cardioplegia Solution in Terms of Postoperative Acute Kidney Injury and Outcome Parameters

Influence of cardioplegic solution on incidence of delirium after CABG surgery: Use of Calafiore blood cardioplegia versusHTK-Bretschneider-solution in a single-center retrospective analysis from 2017 to 2021.

Purpose of the present study is an evaluation of postoperative incidence for delirium after coronary artery bypass surgery (CABG). Study addressed whether application of Histidine-Tryptophan-Ketoglutarate (HTK) solution (Bretschneider) or blood cardioplegia (Calafiore) is associated with increased of postoperative delirium cases. In a retrospective, single center evaluation a total number of 273 patients were enrolled in the study from January 2017 to October 2021. There were 124 patients assigned to the Calafiore groupblood cardioplegic solution (BCC) and 149 patients were included in the Bretschneider group (HTK). The primary endpoint was the postoperative delirium rate in its frequency of occurrence. Definition of the dilirium status was performed using the Confusion Assessment Method in the Intensive Care Unit (CAM-ICU) score during the first three postoperative days. Secondary endpoints were the time intervals of intensive care duration of stay, mechanical ventilation, total extracorporeal circulation, ischemia and reperfusion. Serum levels of the electrolytes Sodium, Potassium, ionized Calcium, and Chloride were monitored. Although no significant difference in delirium status between the groups were noticed, on third postoperative day, delirium rate dependent on cardioplegia solution used (HTK 12.0%; BCC 3.0%; p = .024) and duration of intensive care stay differed (HTK 4.5 vs. BCC 3.0 days; p = .001). Although Ischemic time (HTK 73.0 vs. BCC 83.0 min; p < .001) and reperfusion time (HTK 35.0 vs. Calafiore 24.0 min; p < .001) were extended in the BCC group less cases of delirium were diagnosed. Serum sodium levels after HTK cardioplegic infusion were decreased (HTK 129.68 vs. BCC 138.96 mmol/l; p < .001). The significant difference persists up to the hundredth extracorporeal circulation circuit min(p = .005). The present data suggest an impact of the cardioplegic solution used upon postoperative delirium rates. Optimization of cardiac arrest protocols is needed. Present data encourage further prospective studies regarding the impact of cardioplegic solutions on electrolyte imbalance for postoperative delirium rates in CABG surgery.

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.

Comparison of the efficacy between Del Nido cardioplegia and HTK cardioplegia in Stanford type A aortic dissection patients undergoing open-heart surgery.

Acute Stanford type A aortic dissection is an extremely dangerous and life-threatening cardiovascular disease, usually treated with extracorporeal circulation heart surgery. Histidine-tryptophan-ketoglutarate (HTK) cardioplegia is a protective intracellular myocardial fluid that has been used extensively in different types of extracorporeal circulation surgeries. Del Nido cardioplegia is an extracellular myocardial protection fluid, which was first used in pediatric heart surgery and has been gradually used in a variety of pediatric and adult heart procedures. This study aims to compare the myocardial protection effect between Del Nido and HTK in patients undergoing extracorporeal circulation heart surgery for acute Stanford type A dissection and its impact on patients' prognosis by analyzing selected parameters and clinical manifestations at different time points. Clinical data were collected from 431 patients with acute Stanford type A dissection who were diagnosed and underwent surgery between January 1, 2018 and December 31, 2020 at Xiangya Hospital, Central South University. After excluding some of the data based on exclusion criteria, patients were divided into a HTK group and a Del Nido (DN) group based on type of intraoperative cardioplegia. Propensity score-matching was performed subsequently using the the R statistical software to determine the DN group ( n =40) and HTK group ( n =41). The matching factors were age, sex, hypertension, cardiopulmonary bypass time, and aortic occlusion time. Perioperative data, postoperative complications, blood gas data, and myocardial injury data were collected from the patients, and SPSS 26.0 was used to analyze the data of each group. The DN group had a higher rate of spontaneous cardioversion (41.5% vs 15.0%, P =0.005) and a lower postoperative hospital stay [10.0(8.0,14.0) d vs 13.0(11.0,19.0) d, P <0.05] compared to the HTK group. In terms of changes in blood gas analysis, immediate sodium and potassium concentrations were significantly higher in the DN group than that in the HTK group (both P <0.05). There was no significant difference in myocardial injury indexes between the two groups at different time points (all P >0.05). In terms of postoperative complications, the cardiac complications in DN group were much lower than those in the HTK Group (0 vs 12.5%, P =0.026). Del Nido cardioplegia has similar myocardial protective effects as HTK cardioplegia used in Stanford type A aortic dissection, with a higher rate of cardiac recurrence and fewer cardiac complications. Del Nido cardioplegia should play an important role in future application for acute Stanford type A aortic dissection, but our findings need to be further validated in a large sample of prospective clinical studies.

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.