Histidine-tryptophan-ketoglutarate Group Research Articles

Histidine-trytophan-ketoglutarate cardioplegia reduces inflammatory response and serum levels of myocardial enzymes in newly developed right-thoracotomy rat model

The objective of this research was to establish a rat model for cardiopulmonary bypass (CPB) with cardiac arrest and resuscitation that is both practical and economical and simulates clinical cardiac surgery. Concurrently, the study aimed to evaluate the myocardial protective effects conferred by histidine–tryptophan–ketoglutarate (HTK) cardioplegia. Thirty rats were randomly assigned to three groups: the histidine–tryptophan–ketoglutarate (HTK), 4:1 blood cardioplegia (BC) and del Nido cardioplegia (DN) groups. The cardiopulmonary bypass (CPB) procedure was implemented and sustained for a duration of one hour. Subsequent to the cessation of CPB, the rats were subjected to monitoring and observation for an additional two hours. Following this observation period, the heart and blood samples were procured for subsequent analysis. During CPB, the average hematocrit level was significantly below the typical physiological range (P < 0.001). Histopathological scores were notably lower in the HTK group in contrast to the BC group (P < 0.001) or the DN group (P < 0.001). At 2 h after weaning off CPB, the levels of CK and CKMB in the DN and BC groups were notably elevated compared to the HTK group (P < 0.001). The levels of IL-6 and TNF-α proteins were notably increased in all three groups (P < 0.001), with the BC and DN groups showing higher increases compared to the HTK group (P < 0.001). This compact animal model of cardiopulmonary bypass (CPB) with cardiac arrest and resuscitation might allow for both the study of myocardial ischemia-reperfusion injury as well as cardioprotective strategies. HTK cardioplegia could reduce inflammatory response and serum levels of myocardial enzymes in this newly developed right thoracotomy rat model.

Comparison Between Histidine-Tryptophan-Ketoglutarate Cardioplegia and Cold Blood Cardioplegia for Myocardial Protection in Tetralogy of Fallot Patients Undergoing Surgical Repair: A Randomized Clinical Trial

ObjectivesThis study was conducted to compare the efficacy of histidine-tryptophan-ketoglutarate (HTK) cardioplegia and cold blood cardioplegia (CBC), especially for postoperative right ventricle (RV) function after Tetralogy of Fallot (TOF) repair. DesignRandomized, double-blinded, parallel group, controlled, clinical trial. SettingAin Shams University Hospitals.) ParticipantsA total of 100 children (1-5 years-old) scheduled for TOF repair. InterventionsPatients were allocated (double blinded one: one allocation ratio), to either HTK Group that received HTK cardioplegia (30 ml/kg by antegrade route) or CBC Group that received cold blood cardioplegia with blood to Ringer solution (4:1) in volume of 20 ml/kg. Measurements and Main ResultsThe HTK group showed a statistically significant reduction of the vasoactive inotropic score on admission to pediatric intensive care unit (13.0±4.1) in comparison to CBC (15.5±5.4) with P-value of 0.011 but after 24 hours Vasoactive-Inotropic Score was comparable. Lactate level during the first 24 hours in HTK group (6.2±0.7) mmol/l and (6.9±0.4) mmol/l in CBC group with P-value < 0.0001. Serial troponin measurements were lower in the HTK group (1.49 ± 0.45) in comparison to the CBC group (1.69 ± 0.18) with P-value of 0.005 at the first 72 hours postoperatively. Postoperative echocardiographic assessment of RV function by mean of tricuspid annular plane systolic excursion and myocardial performance index were better in HTK than CBC (P-value<0.05). ConclusionsHTK cardioplegia may offer better cardiac protection to pediatric patients undergoing TOF repair than our institutional standard CBC with better recovery for the hypertrophic RV.

The Potential Neurological Impact of Intraoperative Hyponatremia Using Histidine-Tryptophan-Ketoglutarate Cardioplegia Infusion in Adult Cardiac Surgery.

Background and Objectives: The relationship between histidine-tryptophan-ketoglutarate (HTK)-induced hyponatremia and brain injury in adult cardiac surgery patients is unclear. This study analyzed postoperative neurological outcomes after intraoperative HTK cardioplegia infusion. Materials and Methods: A prospective cohort study was conducted on 60 adult patients who underwent cardiac surgery with cardiopulmonary bypass. Of these patients, 13 and 47 received HTK infusion and conventional hyperkalemic cardioplegia, respectively. The patients' baseline characteristics, intraoperative data, brain injury markers, Mini-Mental State Examination (MMSE) scores, and quantitative electroencephalography (qEEG) data were collected. Electrolyte changes during cardiopulmonary bypass, the degree of hyponatremia, and any associated brain insults were evaluated. Results: The HTK group presented with acute hyponatremia during cardiopulmonary bypass, which was intraoperatively corrected through ultrafiltration and normal saline administration. Postoperative sodium levels were higher in the HTK group than in the conventional cardioplegia group. The change in neuron-specific enolase levels after cardiopulmonary bypass was significantly higher in the HTK group (p = 0.043). The changes showed no significant differences using case-control matching. qEEG analysis revealed a significant increase in relative delta power in the HTK group on postoperative day (POD) 7 (p = 0.018); however, no significant changes were noted on POD 60. The MMSE scores were not significantly different between the two groups on POD 7 and POD 60. Conclusions: HTK-induced acute hyponatremia and rapid correction with normal saline during adult cardiac surgeries were associated with a potential short-term but not long-term neurological impact. Further studies are required to determine the necessity of correction for HTK-induced hyponatremia.

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.

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.

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.

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.

Impact of Histidine-Tryptophan-Ketoglutarate Versus University of Wisconsin Solution on the Outcome of Pancreas Transplant With Cold Ischemic Time ≥12 Hours: A Retrospective Study.

Histidine-tryptophan-ketoglutarate and University of Wisconsin solutions are currently used for pancreas graft preservation. Our hypothesis was whether the use of histidine-tryptophan-ketoglutarate solution is associated with worse pancreas graft survival than University of Wisconsin solution, in general and after prolonged cold ischemic time of ≥12 hours. This retrospective study investigated the impact of static cold storage in histidine-tryptophan-ketoglutarate (n = 133) versus University of Wisconsin (n = 107) solution on outcomes of 240 pancreas transplant procedures. Patient and graft survival rates were compared after 1, 3, and 5 years in both groups. Serum lipase, amylase, and C-reactive protein levels and incidence of surgical complications were evaluated at postoperative week 1. A subgroup analysis of 96 grafts (52 with histidine-tryptophanketoglutarate/44 with University of Wisconsin) with pancreas graft cold ischemic time ≥12 hours was also performed. At mean follow-up of 75.2 ± 9.9 months, both groups demonstrated comparable short- and long-term patient survival. Overall, pancreas graft survival was slightly better in the histidine-tryptophan-ketoglutarate group (Kaplan-Meier analysis, log-rank P = .013). However, the subgroup analysis of grafts with cold ischemic time ≥12 hours showed slightly better pancreatic graft survival in the University of Wisconsin group, although not significantly (log-rank P = .95). Serum lipase and C-reactive protein levels at postoperative week 1 were higher in the histidinetryptophan-ketoglutarate group. Surgical complications were comparable. Multivariable Cox regression analysis identified neither solution as a risk factor affecting patient and graft survival. Although a direct comparison between histidine-tryptophan-ketoglutarate and University of Wisconsin showed better pancreas graft survival with histidine-tryptophan-ketoglutarate, the multivariable analysis showed that the perfusion solution does not significantly influence patient and graft survival. However, in the analysis of transplants with cold ischemic time ≥12 hours, pancreas graft survival was slightly better in the University of Wisconsin group, although not significantly.

Cardioplegia Solution Related Ventricular Pacing Following Orthotopic Heart Transplantation

<h3>Purpose</h3> Multiple solutions are used for heart allograft preservation. University of Wisconsin (UW) remains the most widely used, although there has been increased utilization of histidine-tryptophan-ketoglutarate (HTK). This study investigated differences in the use of postoperative ventricular pacing (VP) at a single center following a change in allograft preservation from UW to HTK . <h3>Methods</h3> We conducted a retrospective study of 42 consecutive patients who underwent orthotopic heart transplantation between January 2017 and December 2018. 21 patients received UW-preserved allografts followed by 21 patients who received HTK-preserved allografts. Patient characteristics, comorbidities and complications were reviewed. Duration of VP and inotropic infusions in the postoperative period were compared between the two groups, UW and HTK. <h3>Results</h3> Table 1 shows pretransplant use of anti-arrhythmics and mechanical support and duration of inotropic support posttransplantation. Figure 1 graphs the number of patients requiring VP from postoperative day 0 to 15. Despite supplemental inotropy in all patients, there was a higher incidence of VP in the first 24 hours in the HTK group compared to UW (43% vs 5%, p=0.01). Preoperative amiodarone use did not correlate with incidence of VP. No patients required a permanent pacemaker. <h3>Conclusion</h3> Multiple studies have been performed investigating the impact of preservation solutions on heart transplant outcomes with mixed results. This hypothesis generating study suggests a higher incidence of bradyarrhythmias requiring VP in HTK-preserved allografts, warranting validation in larger datasets.

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.

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.

Myocardial Protection by Retrograde Application of HTK Solution Compare with Cold Blood Cardioplegic Solution during Heart Valve Surgery

Objective: Cardioplegic solution is one important principle for adequate myocardial protection in cardiac surgery. Bretschneider’s histidine-tryptophan-ketoglutarate (HTK) solution is an intracellular solution while blood cardioplegia solution is an extracellular solution. Both have been used to preserve the myocardium. The present study compared between the two cardioplegic solutions for incidence of ventricular fibrillation after aortic clamp removal in double valve replacement (DVR) and tricuspid annuloplasty (TVA) to assess the effectiveness for myocardial protection. Materials and Methods: A retrospective study was conducted among patients who underwent DVR with TVA operations between January 1, 2013 and June 30, 2017 and divided in two groups at Queen Sirikit Heart Center of the Northeast. The medical records were searched for detailed demographics, preoperative status, operative technique, and post-operative hospital course. Results: Thirty-six patients were included in the present study, 18 patients received HTK solution, the others received blood cardioplegia. The demographic data presented no statistical difference between the two groups. Incidence of ventricular fibrillation after aortic clamp removal occurred in 10 patients (55.6%) in the HTK group, which was more than the cold blood group [five patients (27.78%)]. Cardiopulmonary bypass (CPB) and aortic cross clamp time in the cold blood group was significantly longer than in the HTK group (p&lt;0.001). The peak of Trop-T and CK-MB within six hours after surgery tended to be downward after 24 hours and was not related to perioperative myocardial ischemia in the HTK group. No statistically difference was observed in postoperative outcome, ICU stay, or hospital stay. Conclusion: The use of HTK solution has no significant different outcome compared to conventional cold blood cardioplegia via retrograde route in DVR with TVA operation. There was no significantly different incidence of ventricular fibrillation and there was no evidence of postoperative myocardial infarction. CPB and aortic cross clamp time in the HTK group were shorter than in the cold blood cardioplegia significantly. Keywords: Cardioplegia, HTK, Custodiol, Ventricular fibrillation

Effectiveness of Brain Protection With Histidine-Tryptophan-Ketoglutarate Solutions.

Tissue-protective solutions increase resistance of cells to ischemic conditions. Especially in carotid and aortic arch surgeries where the brain perfusion is at risk, these solutions may be beneficial to prevent ischemic brain damage. This study was designed to demonstrate the effectiveness of histidine-tryptophan-ketoglutarate (HTK) solution in increasing resistance of brain tissue to ischemic conditions. Three separate randomized groups were created, each consisting of eight rabbits. The groups were called the ischemia, HTK and sham groups, respectively. In the ischemia group, temporary brain ischemia was created for 15 minutes by placing clamps on the bilateral subclavian and common carotid arteries. Then the clamps were removed, and the brain was reperfused for 30 minutes. In the HTK group, HTK solution was sent to the brain through the internal carotid artery before the same ischemia-reperfusion protocol was applied. Histopathological analyses using a visual scoring system to assess the degree of ischemic changes and the apoptotic cell index by TUNEL test were performed in all brain tissue samples. Apoptotic cell indices of the HTK (20.6%) and sham (17.8%) groups were lower than the ischemia group (56.8%) (P < .05). Statistically significant differences were detected between all groups in categorical scores (P < .05). It was shown that less ischemic damage occurs in the brain tissue with the use of HTK solution, and it may be a candidate approach to prevent the brain from ischemic insults during cerebrovascular surgery. Further studies are required to demonstrate its exact effectiveness, in terms of dose, duration, and temperature.

Machine perfusion of donor heart with normothermic blood versus hypothermic HTK in preserving coronary endothelium in a porcine model of DCD.

Both machine perfusion (MP) of donor hearts with autologous blood and crystalloid perfusates have advantages and disadvantages. Currently, which of the aforementioned preservation strategies can better preserve the coronary endothelium has not yet been determined. We aim to compare the impact of hypothermic continuous MP with histidine-tryptophan-ketoglutarate (HTK) solution versus normothermic continuous MP with autologous blood on coronary endothelium in a porcine ex vivo model of donation following circulatory death (DCD). DCD pigs underwent circulatory arrest via asphyxiation followed by 30-minute warm ischemia time. Donor hearts were preserved with either hypothermic MP with HTK solution (MP + HTK group; 4 ℃; n=6), or normothermic MP with blood (MP + blood group; 37 ℃; n=6) for 4 hours. After 2-hour ex vivo reperfusion, the assessment of endothelial-dependent (Edep) and -independent (Eind) relaxation of coronary artery, histopathological analysis, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay were performed. Preservation of DCD hearts with MP + Blood strategy significantly improved both Edep and Eind vasorelaxation of coronary artery compared with MP + HTK strategy (maximum relaxation to bradykinin: MP + HTK 80.9%±2.6% vs. MP + Blood 91.9%±1.9%, P<0.001; maximum relaxation to sodium nitroprusside: MP + HTK 97.1%±1.0% vs. MP + Blood 99.8%±0.2%, P<0.05). MP + Blood strategy significantly decreased nitrotyrosine but increased intercellular adhesion molecule-1 immunoreactivity in the coronary artery. The number of TUNEL-positive cells in MP + Blood group were significantly fewer compared with MP + HTK group. Compared with MP + HTK strategy, MP + Blood strategy significantly alleviates coronary endothelial dysfunction during donor heart preservation. This protective effect is associated with the inhibition of apoptosis and nitro-oxidative stress in coronary artery.

A Direct Comparison Between Institut Georges Lopez 1 and Histidine-Tryptophan-Ketoglutarate Preservation Solutions in Liver Transplantation

BackgroundThe Institut Georges Lopez 1 (IGL-1) solution was developed to improve the outcomes of solid organ transplantation. Nevertheless, follow-up of liver transplants using IGL-1-preserved organs is still scarce. AimTo compare morbidity, postoperative complications, and early survival between liver grafts perfused with IGL-1 and those perfused with histidine-tryptophan-ketoglutarate (HTK) solutions. MethodsProspective liver grafts perfused with IGL-1 (n = 65) were paired with a historical control group of recipients whose grafts were preserved with HTK solution (n = 130). The primary endpoint was the sum of the incidence of primary graft dysfunction (PGD) and primary graft nonfunction (PGNF). Secondary endpoints included resource utilization, complications, and survival analysis. ResultsIn the HTK group, 52 patients (40%) exhibited either PGD or PGNF, compared to 20 patients (31%) in the IGL-1 group (P = .208). Patients from the HTK group had higher mean values for cryoprecipitate transfusion (P = .0064), first day serum lactate (P = .0099), higher incidence of vascular complications (11% vs 2% in the IGL-1 group; P = .0226), but a lower incidence of infection (7% vs 28% in the IGL-1 group; P < .0001). The IGL-1 group presented a lower mean aspartate aminotransferase and alanine aminotransferase (ALT) on the first and second postoperative day and a lower ALT on the seventh day. Recipients of grafts perfused with IGL-1 had a better early survival than those whose grafts were perfused with HTK. ConclusionsBoth solutions are safe and present good results. Grafts perfused with IGL-1 showed decreased enzymatic peaks and better short-term survival rates than the HTK group. The use of the IGL-1 solution might be preferable.

Early Outcomes of Custodiol versus Blood Cardioplegia in Coronary Artery Bypass Graft Surgery at Ain Shams University Hospitals

Abstract Background Inadequate myocardial protection in long ischemic periods followed by reperfusion is an issue of concern in cardiac surgery. Cardioplegic solutions improve the tolerance to ischemia and reperfusion by preserving myocardial energy reserves, preventing osmotic and electrolyte imbalances and buffering acidosis. The aim of the study was to compare early outcomes of Histidine–tryptophan–ketoglutarate (HTK) solution versus blood cardioplegia in coronary artery bypass graft surgery at Ain Shams University Hospitals. Methodology This was a retrospective study conducted on patients who underwent isolated elective CABG at the department of cardiothoracic surgery at Ain Shams University Hospitals from the 1stof January, 2017 to the 1st of August, 2018. Results the analysis between these two groups divided as the following: first group who received Histidine–tryptophan–ketoglutarate (HTK) and the second who received conventional blood cardioplegia , There was no statistically significant difference between the two groups of myocardial protection in terms of morbidity and mortality with a p-value &amp;gt;0.05. With a stastically significant increase in Total bypass time with a p value &amp;lt;0.05 and a highly significant difference in terms of post operative Ventilation time and ICU stay which was higher in HTK group with a p-value of &amp;lt; 0.01 between the two groups. Conclusion Conventional blood cardioplegia showed superiority in terms of metabolic recovery based on the incidence of spontaneous defibrillation, ventilation time and ICU stay on the other hand Histidine–tryptophan–ketoglutarate (HTK) cardioplegia is a much more easily administered cardiolplegia technique without the need of preparation or repeated administration. Both Solutions showed efficacy in different areas that could be owed to the small sample size we used which cannot asses the ultimum superiority of one solution over the other .

Type of Preservation Solution, UW or HTK, Has an Impact on the Incidence of Biliary Stricture following Liver Transplantation: A Retrospective Study.

Organ preservation plays a crucial role in the outcome following solid organ transplantation. The aim of this study was to perform a retrospective outcome analysis following liver transplantation using histidine tryptophan ketoglutarate (HTK) or the University of Wisconsin (UW) solutions for liver graft preservation. We retrospectively reviewed data on adult patients who were liver-transplanted at Karolinska University Hospital between 2007 and 2015. There was evaluation of donor and recipient characteristics, pre- and post-transplant blood chemistry tests, biliary and vascular complications, graft dysfunction and nonfunction, and patient and graft survivals. A total of 433 patients were included in the analyses, with 230 and 203 patients having received livers preserved with HTK and UW, respectively. Mean follow-up was 45 ± 29 months for the HTK group and 42.4 ± 26 for the UW group. There was no difference between the two groups either in terms of patient and graft survival, or of results of postoperative blood chemistry, or incidence of arterial complications, early allograft dysfunction, or primary graft nonfunction. However, the incidence of biliary stricture was higher in the UW group (22.7%) versus the HTK group (13.5%; p=0.013). Use of UW and HTK preservation solution in liver transplantation has no impact on patient and graft survival. However, use of HTK solution results in a lower incidence of posttransplant biliary stricture.

233.1: Evaluation of new Baskent university preservation solution for kidney graft during cold ischemia: Preliminary experimental animal study.

Background: Organ damage due to long cold ischemia time remains a hurdle in transplantation. In this preliminary animal study, we compared the new Baskent University Preservation Solution (BUPS) with the University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) solutions. Methods: BUPS composition included electrolytes, raffinose, mannitol, N-acetylcysteine, taurine, adenosine, and ascorbic acid. In experiment 1, kidneys from 50 male Sprague-Dawley rats were placed into BUPS, HTK, or UW solution to assess cold ischemia injury, with biopsies taken at different time points for pathologic evaluation. In experiment 2, to investigate ischemia-reperfusion injury, 5 rats were renal transplant donors to 10 rats and 6 pigs were used as transplant donors-recipients among each other. Results: In experiment 1, no significant cellular injury was shown at up to 3 hours of perfusion with any solution. At 6- to 48-hour perfusion, tubular injury was shown, with lowest injury in BUPS and HTK versus UW and control groups (P<0.01). The BUPS group showed more moderate degree of tubular apoptosis and cytoskeletal rearrangement than the HTK and UW groups at 12-, 24-, and 48-hour perfusion (P<0.01). In experiment 2, after ischemia-reperfusion injury, no significant differences were found between HTK and BUPS groups regarding tubular damage. Although no significant differences were shown regarding tubular cytoskeletal rearrangment and apoptosis in pig reperfusion group with BUPS versus HTK, significant differences were shown with these solutions in other groups. Conclusions: Tubular damage during ischemia-reperfusion injury (cytoskeletal disruption, increased apoptosis) were lower with BUPS. BUPS can be a cost-effective perfusion solution in transplantation.