Ventricular Fibrillation After Release of an Aortic Cross-Clamp in Valvular Surgery: Independent Risk Factors, Outcomes, and Incidence from Access Routes

Background Predictors and clinical outcomes of VF-ACC and the relative VF-ACC incidence with various access routes have not been well documented. This study aimed to identify predictors, clinical outcomes, and relative incidences of ventricular fibrillation after the release of an aortic cross-clamp (VF-ACC) with various access routes in valvular surgery.Patients and methods In this single-center and retrospective cohort study, we screened 228 consecutive patients undergoing valve surgery, and a total of 119 patients were included in the study. The primary outcomes were the relative incidence and predictors of VF-ACC with access routes, and secondary endpoints included effects of VF-ACC on 30-day mortality, perioperative ventricular arrhythmias (VAs), and heart failure with ejection fraction < 50% (HFEF < 50%).Results VF-ACC incidence varied on the basis of access routes. VF-ACC occurred in 58.3% of patients with aortic valve replacement via transverse aortotomy (TAo-AVR), in 48.6% of patients with aortic and mitral replacements via transseptal and transverse aortotomy access (TSAo-MAVR), and in 20% of patients with mitral valve replacement via transseptal access (TS-MVR). Seven independent risk factors were identified: HTK solution (AOR: 4.90, p = 0.002), smoking status (AOR: 6.30, p = 0.001), cerebrovascular disease (CBD) [(AOR: 7.08, p = 0.022)], regional wall motion abnormality (RWMA) [(AOR: 8.33, p < 0.001)], perioperative VAs (AOR: 4.85, p = 0.001), HFEF < 50% (AOR: 5.66, p = 0.002), and left ventricular mass index (LVMI) [(AOR: 0.962, CI: 0.941–0.984)].Conclusions VF-ACC was the most common in TAo-AVR and the least common in TS-MVR. HTK solution, smoking status, CBD, perioperative VAs, HFEF < 50%, and RWMA were associated with an increased risk of VF-ACC, and low LVMI acted as a protective factor. Patients with VF-ACC commonly experienced perioperative VAs or HFEFs < 50%.Clinical trial registration: ChiCTR2100050961.

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&lt;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.

Perfusion, cryopreservation, and nanowarming of whole hearts using colloidally stable magnetic cryopreservation agent solutions

Nanowarming of cryopreserved organs perfused with magnetic cryopreservation agents (mCPAs) could increase donor organ utilization by extending preservation time and avoiding damage caused by slow and nonuniform rewarming. Here, we report formulation of an mCPA containing superparamagnetic iron oxide nanoparticles (SPIONs) that are stable against aggregation in the cryopreservation agent VS55 before and after vitrification and nanowarming and that achieve high-temperature rise rates of up to 321°C/min under an alternating magnetic field. These SPIONs and mCPAs have low cytotoxicity against primary cardiomyocytes. We demonstrate successful perfusion of whole rat hearts with the mCPA and removal using Custodiol HTK solution, even after vitrification, cryostorage in liquid nitrogen for 1 week, and nanowarming under an alternating magnetic field. Quantification of SPIONs in the hearts using magnetic particle imaging demonstrates that the formulated mCPAs are suitable for perfusion, vitrification, and nanowarming of whole organs with minimal residual iron in tissues.

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<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

Adenosine A2a Receptor Stimulation Attenuates Ischemia-Reperfusion Injury and Improves Survival in A Porcine Model of DCD Liver Transplantation

Orthotopic liver transplantation (OLT) using allografts from donation after circulatory death (DCD) is potentially associated with compromised clinical outcomes due to ischemia-reperfusion injury (IRI)-induced organ damage and graft-related complications. The aim of this study was to provide in vivo data on the effects of adenosine A2a receptor stimulation in a clinically relevant large animal model of DCD liver transplantation. Cardiac arrest was induced in German Landrace pigs (n = 10; 20–25 kg). After 30 min of warm ischemia, the donor liver was retrieved following a cold flush with 3 L of histidine-tryptophan-ketoglutarate-HTK solution. Animals of the treatment group (n = 5/group) received a standard dose of the selective adenosine receptor agonist CGS 21680 added to the cold flush. All grafts were stored for 4.5 h at 4 °C in HTK-solution before OLT. Hepatocellular injury, apoptosis, protein kinase A-PKA activity, graft microcirculation, liver function, and animal survival were assessed. Compared to untreated livers, adenosine A2a receptor stimulation resulted in improved tissue microcirculation (103% ± 5% vs. 38% ± 4% compared to baseline; p < 0.05), accelerated functional recovery of the graft (indocyanine green-plasma disappearance rate (ICG-PDR) of 75% ± 18% vs. 40% ± 30% after 3 h), increased PKA activity ratio (56% ± 3% vs. 32% ± 3%; p < 0.001 after 1 h), and consequently reduced tissue necrosis and apoptosis. The potent protective effects were clinically manifested in significantly improved survival in the treatment group after 72 h (100% vs. 40%; p = 0.04). The ex vivo administration of adenosine A2a receptor agonist during the back-table flush mitigates IRI-mediated tissue damage and improves functional graft recovery and survival in a large animal model of DCD liver transplantation.

HTK-N: Modified Histidine-Tryptophan-Ketoglutarate Solution—A Promising New Tool in Solid Organ Preservation

To ameliorate ischemia-induced graft injury, optimal organ preservation remains a critical hallmark event in solid organ transplantation. Although numerous preservation solutions are in use, they still have functional limitations. Here, we present a concise review of a modified Histidine-Tryptophan-Ketoglutarate (HTK) solution, named HTK-N. Its composition differs from standard HTK solution, carrying larger antioxidative capacity and providing inherent toxicity as well as improved tolerance to cold aiming to attenuate cold storage injury in organ transplantation. The amino acids glycine, alanine and arginine were supplemented, N-acetyl-histidine partially replaced histidine, and aspartate and lactobionate substituted chloride. Several in vitro studies confirmed the superiority of HTK-N in comparison to HTK, being tested in vivo in animal models for liver, kidney, pancreas, small bowel, heart and lung transplantation to adjust ingredients for required conditions, as well as to determine its innocuousness, applicability and potential advantages. HTK-N solution has proven to be advantageous especially in the preservation of liver and heart grafts in vivo and in vitro. Thus, ongoing clinical trials and further studies in large animal models and consequently in humans are inevitable to show its ability minimizing ischemia-induced graft injury in the sequel of organ transplantation.

Effectiveness of Brain Protection With Histidine-Tryptophan-Ketoglutarate Solutions

Background: 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. Methods: 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. Results: 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). Conclusions: 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.