Comparison of Del Nido (a different application) and crystalloid blood cardioplegia on arrhythmia and early results.

BACKGROUND: The results of the use of del-Nido(DN) solution using a different method or crystalloid blood cardioplegia in coronary bypass patients were compared. We aimed to investigate the effects on intraoperative and postoperative arrhythmias, arrhythmia durations and early results. METHODS: The study included 175 patients using crystalloid blood cardioplegia (Group 1) and 150 patients using DN solution(Group 2). In the DN group, 75% of the calculated plegia dose was given first. the remaining part was applied by giving from grafts. Intraoperative/postoperative data were compared. RESULTS: There was no significant difference between the groups in terms of demographic characteristics. Preop troponin level was similar.(p = 0.190) However, there was a statistical difference between the postoperative 6th hour.(p = 0.001) There was no difference in troponin values at the postoperative 24th hour. (p = 0.631) Spontaneous rhythm occurred at the cardiopulmonary by pass (CPB) weaning stage in most of the patients in Group 2 (95.3%). Although the need for temporary pacing was less in Group 2, it was not significant.(p = 0.282) No patient required permanent pacing. CPB duration, cross clamp times and intraoperative glucose levels, intensive care follow-up times and hospitalization times were found to be shorter in Group 2. Although the postoperative atrial fibrillation frequency was similar (p = 0.261), the time to return to sinus was lower in Group 2.(p = 0.001). CONCLUSION: The use of DN cardioplegia solution provides significant positive contributions to avoid arrhythmias compared to crystalloid blood cardioplegia. DN solution applied with this method may contribute to reducing the anxieties associated with its use in isolated coronary artery bypass surgery.

A novel versatile concept of cardioplegia delivery in cardiac surgery: The ReverseTWO cardioplegia circuit system.

Nowadays, the necessity of having a cardioplegia circuit capable of being adapted in order to administer different types of cardioplegia is strategically fundamental, both for the perfusionist and for the cardiac surgeon. This allows to avoid cutting tubes, guarantees sterility and, most of all, limits the number of cardioplegia circuits for the different strategies of cardiac arrest. The novel "ReverseTWO cardioplegia circuit system" is the development of the precedent "Reverse system" where mainly the 4:1 and crystalloid cardioplegia were used, It has the advantage of allowing immediate change of cardioplegia set-up versus four types of cardioplegia technique, when the strategy is unexpectedly changed before the beginning of cardiopulmonary bypass (CPB), is safe and enables the perfusionist to use one single custom pack of cardioplegia. Two pediatric roller pumps are usually used in our centre for cardioplegia administration; they have a standardized calibration (the leading with » inch and the follower with 1/8 inch) and the circuit consequently has two different tube diameters for the two different pumps. The presence in the circuit of two different shunts coupled with two different coloured clamps allows the immediate set-up for different cardioplegia administration techniques utilizing a colour-coding mechanism The aim of this manuscript is to present the new ReverseTWO Circuit. This novel system allows to administer four different cardioplegic solutions (4:1, 1:4, crystalloid, ematic) based on multiple tubes, which can be selectively clamped, identified through a color-coding method. The specificity of this circuit is the great versatility, which leads to numerous advantages, such as reduced risk of perfusion accident and reduced costs related not only to the purchase of different cardioplegia kits but also to the storage. https://youtu.be/ovJBE4ok2Ds.

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.

Comparison of Cardioplegic Solutions in Coronary Bypass Surgery Over Autophagy and Apoptosis Mechanisms. / Comparação de Soluções Cardioplégicas em Cirurgia de Revascularização Miocárdica sobre Mecanismos de Autofagia e Apoptose.

BACKGROUND: Coronary artery disease (CAD) due to myocardial ischemia causes permanent loss of heart tissue. OBJECTIVES: We aimed to demonstrate the possible damage to the myocardium at the molecular level through the mechanisms of autophagy and apoptosis in coronary bypass surgery patients. METHODS: One group was administered a Custodiol cardioplegia solution, and the other group was administered a Blood cardioplegia solution. Two myocardial samples were collected from each patient during the operation, just before cardiac arrest and after the aortic cross-clamp was released. The expressions of autophagy and apoptosis markers were evaluated. The level of statistical significance adopted was 5%. RESULTS: The expression of the BECLIN gene was significant in the myocardial tissues in the BC group (p=0.0078). CASPASE 3, 8, and 9 gene expression levels were significantly lower in the CC group. Postoperative TnT levels were significantly different between the groups (p=0.0072). CASPASE 8 and CASPASE 9 gene expressions were similar before and after aortic cross-clamping (p=0.8552, p=0.8891). In the CC group, CASPASE 3, CASPASE 8, and CASPASE 9 gene expression levels were not found to be significantly different in tissue samples taken after aortic cross-clamping (p=0.7354, p=0.0758, p=0.4128, respectively). CONCLUSIONS: With our findings, we believe that CC and BC solutions do not have a significant difference in terms of myocardial protection during bypass operations.

FUNDAMENTO: A doença arterial coronariana (DAC) devido à isquemia miocárdica causa perda permanente de tecido cardíaco. OBJETIVOS: Nosso objetivo foi demonstrar o possível dano ao miocárdio em nível molecular através dos mecanismos de autofagia e apoptose em pacientes submetidos à cirurgia de revascularização miocárdica. MÉTODOS: Um grupo recebeu uma solução de cardioplegia Custodiol e o outro grupo uma solução de cardioplegia sanguínea. Duas amostras miocárdicas foram coletadas de cada paciente durante a operação, imediatamente antes da parada cardíaca e após a liberação do pinçamento aórtico. Foram avaliadas as expressões de marcadores de autofagia e apoptose. O nível de significância estatística adotado foi de 5%. RESULTADOS: A expressão do gene BECLIN foi significativa nos tecidos miocárdicos do grupo CS (p=0,0078). Os níveis de expressão dos genes CASPASE 3, 8 e 9 foram significativamente menores no grupo CC. Os níveis pós-operatórios de TnT foram significativamente diferentes entre os grupos (p=0,0072). As expressões dos genes CASPASE 8 e CASPASE 9 foram semelhantes antes e depois do pinçamento aórtico (p=0,8552, p=0,8891). No grupo CC, os níveis de expressão gênica de CASPASE 3, CASPASE 8 e CASPASE 9 não foram significativamente diferentes em amostras de tecido coletadas após pinçamento aórtico (p=0,7354, p=0,0758, p=0,4128, respectivamente). CONCLUSÕES: Com nossos achados, acreditamos que as soluções CC e CS não apresentam diferença significativa em termos de proteção miocárdica durante as operações de by-pass.

Oxygen Nanocarriers for Improving Cardioplegic Solution Performance: Physico-Chemical Characterization.

Nanocarriers for oxygen delivery have been the focus of extensive research to ameliorate the therapeutic effects of current anti-cancer treatments and in the organ transplant field. In the latter application, the use of oxygenated cardioplegic solution (CS) during cardiac arrest is certainly beneficial, and fully oxygenated crystalloid solutions may be excellent means of myocardial protection, albeit for a limited time. Therefore, to overcome this drawback, oxygenated nanosponges (NSs) that can store and slowly release oxygen over a controlled period have been chosen as nanocarriers to enhance the functionality of cardioplegic solutions. Different components can be used to prepare nanocarrier formulations for saturated oxygen delivery, and these include native α-cyclodextrin (αCD), αcyclodextrin-based nanosponges (αCD-NSs), native cyclic nigerosyl-nigerose (CNN), and cyclic nigerosyl-nigerose-based nanosponges (CNN-NSs). Oxygen release kinetics varied depending on the nanocarrier used, demonstrating higher oxygen release after 24 h for NSs than the native αCD and CNN. CNN-NSs presented the highest oxygen concentration (8.57 mg/L) in the National Institutes of Health (NIH) CS recorded at 37 °C for 12 h. The NSs retained more oxygen at 1.30 g/L than 0.13 g/L. These nanocarriers have considerable versatility and the ability to store oxygen and prolong the amount of time that the heart remains in hypothermic CS. The physicochemical characterization presents a promising oxygen-carrier formulation that can prolong the release of oxygen at low temperatures. This can make the nanocarriers suitable for the storage of hearts during the explant and transport procedure.

The impact of del Nido cardioplegia solution on blood morphology parameters.

BACKGROUND: Crystalloid cardioplegic solutions are believed to reduce hemoglobin significantly and increase the transfusion rate. However, recent reports indicate that the del Nido cardioplegia may preserve blood morphology parameters. METHODS: In "The del Nido versus cold blood cardioplegia in aortic valve Replacement" trial patients undergoing aortic valve replacement were randomized into the del Nido (DN) or cold blood cardioplegia (CB) group. For the subanalysis, patients who underwent blood transfusions were excluded from the study. Red blood cell (RBC) count, hemoglobin, white blood cell (WBC) count and platelet (PLT) count were measured before the surgery, 24-, 48-, and 96 hours postoperatively. Furthermore, percental variation in first-last measure was compared in groups. In addition, indexed normalized ratio (INR) and activated partial thromboplastin time (aPTT) were compared preoperatively and 24 hours after the surgery. RESULTS: Eighteen (24%) patients from the del Nido group and 22 (29.3%) patients from the CB group received blood product transfusions (p = 0.560) and were excluded from further analysis. As such, 57 patients remained in DN group and 53 patients remained in CB group. No difference was found in RBC, hemoglobin, WBC, and platelet count in time intervals. Percental variation in first-last measure revealed higher fall in RBC (p = 0.0024) and hemoglobin (p = 0.0028) in the CB group. No difference was shown in preoperative and 24-hour postoperative INR and aPTT. CONCLUSIONS: The del Nido cardioplegia does not decrease blood morphology parameters when compared to cold blood cardioplegia and may be used alternatively regardless of bleeding and coagulopathy risk.

Histidine-tryptophan-ketoglutarate solution versus multidose cardioplegia for myocardial protection in cardiac surgeries: a systematic review and meta-analysis.

BACKGROUND: Surgical procedures in the heart requires protection of the heart from ischemia-reperfusion injury. Cardioplegia is the primary myocardial protective method in use. Histidine-tryptophan-ketoglutarate (HTK) solution is an intracellular cardioplegic solution that was initially used to preserve organs for transplantation. METHODS: A systematic electronic search was conducted in July 2021, in four databases; PubMed, Scopus, Web of Science, and Cochrane Library for eligible randomized controlled trials. The results were screened and the eligible trials were identified. Thereafter, the relevant data were extracted and pooled as mean difference or risk ratio, and 95% confidence interval in an inverse variance method using RevMan software. RESULTS: This review included 12 trials (n = 1327). HTK solution has resulted significantly in shorter intensive care unit stay (MD = - 0.09; 95% CI [- 0.15, - 0.03], p = 0.006), and shorter hospital stay (MD = - 0.51; 95% CI [- 0.71, - 0.31], p < 0.00001). Moreover, the patients who received the HTK solution had significantly lower levels of creatine kinase (after 4-7 h (MD = - 157.52; 95% CI [- 272.31, - 42.19], p = 0.007), and 24 h (MD = - 136.62; 95% CI [- 267.20, - 6.05], p = 0.04)), as well as creatine kinase muscle brain band (after 44-48 h (MD = - 3.35; 95% CI [- 5.69, - 1.02], p = 0.005)). CONCLUSION: HTK solution had the same efficacy and safety as other cardioplegic solutions in most of the clinical parameters. Furthermore, the solution showed superiority in fastening the recovery and protecting the myocardium at the biochemical level. HTK solution provides longer myocardial protection; therefore, it limits surgical interruption. HTK solution can be used as an alternative to the currently used cardioplegic solutions.

Normothermic blood polarizing versus depolarizing cardioplegia in a porcine model of cardiopulmonary bypass.

OBJECTIVES: We have previously demonstrated beneficial cardiac protection with hypothermic polarizing cardioplegia compared to a hyperkalemic depolarizing cardioplegia. In this study, a porcine model of cardiopulmonary bypass was used to compare the protective effects of normothermic blood-based polarizing and depolarizing cardioplegia during cardiac arrest. METHODS: Thirteen pigs were randomized to receive either normothermic polarizing (n = 8) or depolarizing (n = 5) blood-based cardioplegia. After initiation of cardiopulmonary bypass, normothermic arrest (34°C, 60 min) was followed by 60 min of on-pump and 90 min of off-pump reperfusion. Primary outcome was myocardial injury measured as arterial myocardial creatine kinase concentration. Secondary outcome was haemodynamic function and the energy state of the hearts. RESULTS: During reperfusion, release of myocardial creatine kinase was comparable between groups (P = 0.36). In addition, most haemodynamic parameters showed comparable results between groups, but stroke volume (P = 0.03) was significantly lower in the polarizing group. Adenosine triphosphate levels were significantly (18.41 ± 3.86 vs 22.97 ± 2.73 nmol/mg; P = 0.03) lower in polarizing hearts, and the requirement for noradrenaline administration (P = 0.002) and temporary pacing (6 vs 0; P = 0.02) during reperfusion were significantly higher in polarizing hearts. CONCLUSIONS: Under normothermic conditions, polarizing blood cardioplegia was associated with similar myocardial injury to depolarizing blood cardioplegia. Reduced haemodynamic and metabolic outcome and a higher need for temporary pacing with polarized arrest may be associated with the blood-based dilution of this solution.

Oral application of levosimendan before ischaemia/reperfusion with or without cardioplegic arrest in rats.

OBJECTIVES: Clinical studies have indicated minor beneficial effects of the calcium sensitizer levosimendan on clinical outcomes in patients undergoing cardiac surgery. Here, the influence of levosimendan administered 24 h before cardiac arrest on myocardial function was examined in rat hearts perfused in a Langendorff model. METHODS: Levosimendan (Levo group) or NaCl (control group) was administered to 53 rats via drinking water 24 h prior to mounting excised hearts on a Langendorff apparatus. Cardiac arrest with or without cardioplegia was induced in both groups; another set of hearts was perfused continuously. During 90-min reperfusion at 36°C, functional parameters were measured and normalized to baseline values. Troponin I was quantified in coronary sinus effluent, and the functionality of isolated cardiomyocytes was studied. RESULTS: Oral application of levosimendan showed therapeutic efficacy. Baseline values were similar in the Levo and NaCl groups except for coronary flow. After ischaemia and reperfusion, Levo hearts did not recover better than NaCl hearts {left ventricular derived pressure: 63 [standard deviation (SD): 36.2] vs 46 (SD: 41.8)% baseline; P = 0.386}, In hearts exposed to cardioplegia, functional recovery only slightly differed in the Levo and NaCl groups [left ventricular derived pressure: 69.96 (SD: 12.7) vs 51.89 (SD: 28.1)% baseline; P = 0.09]. Cell shortening of cardiomyocytes isolated from hearts exposed to ischaemia or perfusion was better in Levo groups [cell shortening: 7.65 (SD: 1.95) %; 7.8 (SD: 1.79)% vs 6.28 (SD: 1.67)%; 6.5 (SD: 1.87)%, P < 0.001]; this benefit was absent in cardioplegia-treated hearts. CONCLUSIONS: Levosimendan applied orally before ischaemia/reperfusion improves functional recovery, but this effect is only moderate when cardioplegia is included. Differences between hearts exposed to cardioplegia or to global ischaemia may indicate why levosimendan-related beneficial effects do not directly translate into better clinical outcome.

Custodiol versus Blood Cardioplegia: Comparison of Myocardial Immunohistochemical Analysis and Clinical Outcomes.

INTRODUCTION: Custodiol (histidine-tryptophan-ketoglutarate) and repetitive blood cardioplegia are the solutions for myocardial protection and cardiac arrest. In this study, we aimed to compare immunohistochemical analysis, clinical outcomes, and cardiac enzyme values of Custodiol and blood cardioplegia groups. METHODS: This was a randomized prospective study consisting of 2 groups and 20 patients, 10 patients for each group, who underwent mitral and mitral/tricuspid valve surgery. Group 1 was formed for Custodiol cardioplegia and group 2 for blood cardioplegia. Perioperative and postoperative cardiac events were recorded, cardiac enzymes were analyzed with intervals, and myocardial samples were taken for immunohistochemical analysis. Recorded data were statistically evaluated. RESULTS: There was no significant difference for the Custodiol and blood cardioplegia groups in perioperative and postoperative cardiac performance and adverse events. Cardiac enzyme analysis showed no significant difference between groups. However, two parameters (eNOS, Bcl-2) were in favor of the Custodiol group in immunohistochemical studies. Custodiol performed better in cellular oxidative stress resistance and cellular viability. CONCLUSION: Clinical outcomes and cardiac enzyme analysis results were similar regarding myocardial protection. However, Custodiol performed better in the immunohistochemical analysis.

St. Thomas Modified Cardioplegia Effects on Myoblasts' Viability and Morphology.

Background and Objectives: The cardioplegic arrest of the heart during cardiosurgical procedures is the crucial element of a cardioprotection strategy. Numerous clinical trials compare different cardioplegic solutions and cardioprotective protocols, but a relatively small number of papers apply to in vitro conditions using cultured cells. This work aimed to analyze whether it is possible to use the rat heart myocardium cells as an in vitro model to study the protective properties of St. Thomas cardioplegia (ST2C). Methods: The rat heart myocardium cells-H9C2 were incubated with cold cardioplegia for up to 24 h. After incubation, we determined: viability, confluency, and cell size, the thiol groups' level by modifying Ellman's method, Ki67, and Proliferating Cell Nuclear Antigen expression (PCNA). The impact on cells' morphology was visualized by the ultrastructural (TEM) study and holotomograpic 3D imaging. Results: The viability and confluency analysis demonstrated that the safest exposure to ST2C, should not exceed 4h. An increased expression of Ki67 antigen and PCNA was observed. TEM and 3D imaging studies revealed vacuolization after the longest period of exposure (24). Conclusions: According to obtained results, we conclude that STC can play a protective role in cardiac surgery during heart arrest.

del Nido cardioplegia better preserves cardiac diastolic function but histidine-tryptophan-ketoglutarate is better for endothelial function.

OBJECTIVES: The effectiveness of myocardial protection of cardioplegia has been a matter of debate for decades. This study was designed to compare cardiac and endothelial protection of 3 clinically used cardioplegias: del Nido cardioplegia (DNC), histidine-tryptophan-ketoglutarate (HTK) and blood cardioplegia (BC) followed by HTK (BC + HTK) in a rat model of ischaemia/reperfusion (I/R). METHODS: Sixty male Wistar rats were subjected to either 120 min of global ischaemia at 4°C followed by 90 min of reperfusion (I/R) at 37°C or no I/R (control) in a Langendorff apparatus and were randomly allocated to 5 groups: control, I/R, DNC, HTK and BC + HTK. Cold cardioplegia solutions were administered at doses of 20 ml/kg for DNC and HTK or 10 ml/kg for BC followed by HTK. Haemodynamic parameters were continuously recorded using an intraventricular balloon. The endothelium-dependent relaxation to acetylcholine was measured in the left anterior descending artery using a myograph. Protein expression of cardiac troponin T (cTnT) and creatine kinase MB was determined by western blot. RESULTS: During reperfusion, HTK had higher left ventricular systolic pressure whereas DNC had lower left ventricular end-diastolic pressure, better left ventricular developed pressure and best +dp/dtmax and -dp/dtmax than the other 2 groups but the differences disappeared at the end of the reperfusion. HTK or BC + HTK preserves the acetylcholine-induced endothelium-dependent relaxation better than DNC (Emax = 48.2 ± 8.0% in DNC vs 75.0 ± 8.0% in HTK, P < 0.05; vs 96.9 ± 3.5% in BC + HTK, P < 0.001). The protein levels of cTnT and creatine kinase MB were downregulated in the 3 groups. CONCLUSIONS: All 3 cardioplegias prevented myocardial damage against I/R injury at the end of reperfusion. DNC demonstrated better preserved diastolic function of the left ventricle whereas HTK or BC + HTK showed better preserved coronary endothelial function. These findings may suggest that currently no 'perfect' cardioplegia exists and that exploration for the 'perfect' cardioplegia is needed.

Diazoxide preserves myocardial function in a swine model of hypothermic cardioplegic arrest and prolonged global ischemia.

OBJECTIVE: Adenosine triphosphate potassium sensitive channels provide endogenous myocardial protection via coupling of cell membrane potential to myocardial metabolism. Adenosine triphosphate potassium sensitive channel openers, such as diazoxide, mimic ischemic preconditioning, prevent cardiomyocyte swelling, preserve myocyte contractility after stress, and provide diastolic protection. We hypothesize that diazoxide combined with hyperkalemic cardioplegia provides superior myocardial protection compared with cardioplegia alone during prolonged global ischemia in a large animal model. METHODS: Twelve pigs were randomized to global ischemia for 2 hours with a single dose of cold blood (4:1) hyperkalemic cardioplegia alone (n = 6) or with diazoxide (500 µmol/L) (n = 6) and reperfused for 1 hour. Cardiac output, myocardial oxygen consumption, left ventricular developed pressure, left ventricular ejection fraction, diastolic function, myocardial troponin, myoglobin, markers of apoptosis, and left ventricular infarct size were compared. RESULTS: Four pigs in the cardioplegia alone group could not be weaned from cardiopulmonary bypass. There were no differences in myoglobin, troponin, or apoptosis between groups. Diazoxide preserved cardiac output versus control (74.5 vs 18.4 mL/kg/min, P = .01). Linear mixed regression modeling demonstrated that the addition of diazoxide to cardioplegia preserved left ventricular developed pressure by 36% (95% confidence interval, 9.9-61.5; P < .01), dP/dt max by 41% (95% confidence interval, 14.5-67.5; P < .01), and dP/dt min by 33% (95% confidence interval, 8.9-57.5; P = .01). It was also associated with higher (but not significant) myocardial oxygen consumption (3.7 vs 1.4 mL O2/min, P = .12). CONCLUSIONS: Diazoxide preserves systolic and diastolic ventricular function in a large animal model of prolonged global myocardial ischemia. Diazoxide as an adjunct to hyperkalemic cardioplegia may allow safer prolonged ischemic times during increasingly complicated cardiac procedures.

Re-dosing of del Nido cardioplegia in adult cardiac surgery requiring prolonged aortic cross-clamp.

OBJECTIVES: Few data exist on the use of del Nido cardioplegia in adults, specifically during operations requiring prolonged aortic cross-clamp. In this pilot study, we evaluate outcomes of patients undergoing surgery with cross-clamp time >3 h based on re-dosing strategy, using either full dose (FD; 1:4 blood to crystalloid ratio) or dilute (4:1 blood to crystalloid ratio) solution. METHODS: Consecutive adult patients (>18 years) undergoing cardiac surgery from 2012 to 2018 with cross-clamp time >3 h were reviewed. Patients were excluded if del Nido cardioplegia was not used. Patients were categorized into FD or dilute groups based on re-dosing solution. Propensity score matching was used to control for baseline differences between groups. The primary endpoint was in-hospital mortality. Other outcomes examined included: postoperative mechanical support, arrhythmia, stroke, dialysis and cardiac function. RESULTS: Included for analysis were 173 patients (115 male) with median age of 63.8 (interquartile range 53.9-73.1). Major comorbidities included diabetes (45), cerebrovascular disease (34), hypertension (131), atrial fibrillation (52) and previous cardiac surgery (83). There were 108 patients (62%) who received FD re-dosing, while 65 (38%) received dilute. A greater proportion of patients in the dilute group received retrograde delivery, for both induction (32/108 vs 39/65, P < 0.001) and re-dose (50/108 vs 53/65, P < 0.001). After propensity score matching, in-hospital mortality was not different between groups (6/48 vs 1/48, P = 0.131). There were no differences in rates of postoperative mechanical circulatory support, stroke, left ventricular ejection fraction or right ventricle dysfunction. CONCLUSIONS: Del Nido cardioplegia has been used in complex cardiac surgery requiring prolonged cross-clamp. Re-dosing can be performed with either FD or dilute del Nido solution with no statistical difference in outcomes.

Prompt Graft Cooling Enhances Cardioprotection during Heart Transplantation Procedures through the Regulation of Mitophagy.

A complete and prompt cardiac arrest using a cold cardioplegic solution is routinely used in heart transplantation to protect the graft function. However, warm ischemic time is still inevitable during the procedure to isolate donor hearts in the clinical setting. Our knowledge of the mechanism changes prevented by cold storage, and how warm ischemia damages donor hearts, is extremely poor. The potential consequences of this inevitable warm ischemic time to grafts, and the underlying potential protective mechanism of prompt graft cooling, have been studied in order to explore an advanced graft protection strategy. To this end, a surgical procedure, including 10-15 min warm ischemic time during procurement, was performed in mouse models to mimic the clinical situation (Group I), and compared to a group of mice that had the procurement performed with prompt cooling procedures (Group II). The myocardial morphologic changes (including ultrastructure) were then assessed by electron and optical microscopy after 6 h of cold preservation. Furthermore, syngeneic heart transplantation was performed after 6 h of cold preservation to measure the graft heart function. An electron microscopy showed extensive damage, including hypercontracted myofibers with contraction bands, and damaged mitochondria that released mitochondrial contents in Group I mice, while similar patterns of damage were not observed in the mice from Group II. The results from both the electron microscopy and immunoblotting verified that cardiac mitophagy (protective mitochondrial autophagy) was present in the mice from Group II, but was absent in the mice from Group I. Moreover, the mice from Group II demonstrated faster rebeating times and higher beating scores, as compared to the mice from Group I. The pressure catheter system results indicated that the graft heart function was significantly more improved in the mice from Group II than in those from Group I, as demonstrated by the left ventricle systolic pressure (31.96 ± 6.54 vs. 26.12 ± 8.87 mmHg), the +dp/dt (815.6 ± 215.4 vs. 693.9 ± 153.8 mmHg/s), and the -dp/dt: (492.4 ± 92.98 vs. 418.5 ± 118.9 mmHg/s). In conclusion, the warm ischemic time during the procedure impaired the graft function and destroyed the activation of mitophagy. Thus, appropriate mitophagy activation has emerged as a promising therapeutic target that may be essential for graft protection and functional improvement during heart transplantation.

Effects of Del Nido and Terminal Warm Blood Cardioplegia on Myocardial Protection and Rhythm in Isolated CABG Patients.

OBJECTIVE: To investigate the effect of using del Nido cardioplegia+terminal hot-shot blood cardioplegia on myocardial protection and rhythm in isolated coronary bypass patients. MATERIAL AND METHODS: A total of 122 patients were given cold (+4-8C') del Nido cardioplegia antegrade and evaluated. Del Nido+terminal warm blood cardioplegia (TWBCP) was applied to 63 patients out of 122 patients, while del Nido cardioplegia alone was applied to the other 59 patients. The preoperative and postoperative data of the patients were recorded and compared. RESULTS: There was a significant statistical difference between the groups, in terms of volume with more cardioplegia in the del Nido+terminal warm blood cardioplegia group. Although there was no significant difference between cardiac arrest times in both groups, a statistically significant difference was found in the del Nido+terminal warm blood cardioplegia group in the starting to work time of the heart. No difference found between the groups regarding myocardial preservation. CONCLUSIONS: We can add a return to spontaneous sinus rhythm to the advantages of terminal warm blood cardioplegia and del Nido cardioplegia in literature. We think it would be a good strategy to extend the safe ischemic time limit of del Nido to 120 minutes with a terminal warm blood cardioplegia. It seems that cardioplegia techniques that will be developed by adding the successful and superior results of crystalloid cardioplegia applications, such as single dose del Nido in various open heart surgery operations and the superior myocardial return effects of terminal warm blood cardioplegia, will be used routinely in the future.

Validation of using cardioplegic solutions for preserving cardiac function in isolated rabbit heart assays.

INTRODUCTION: Cardioplegic solutions were first developed to preserve heart function during cardiac surgeries and heart transplants but have application in the nonclinical setting. Due to lack of lab space in the vivarium, cardioplegic solution was used to conserve cardiac function for ex-vivo studies performed in a separate building. All studies in this report were conducted with isolated female rabbit hearts (IRHs) via retrograde perfusion using the Langendorff apparatus to investigate if cardioplegia usage affects cardiac function. METHODS: Cardioplegia was achieved with a hyperkalemia (27 mM KCL) solution kept at 4 °C. Cardiac function was assessed by measuring ECG parameters, left ventricular contractility, and coronary flow under constant perfusion pressure. IRHs were cannulated with Krebs Henseleit buffer (KH) either fresh or after cardioplegic solution storage (C-IRH). Three comparisons were performed with and without cardioplegia; (i) direct side-by side studies of cardiac function; (ii) pharmacological responses to typical ion channels blockers, dofetilide, flecainide, and diltiazem; (iii) retrospective evaluation of cardiac functions in a large sample of hearts. RESULTS: In the side-by-side comparisons, cardioplegia-stored IRHs (C-IRH; storage time 90 min) had similar electrocardiographic (ECG) and hemodynamic parameters to fresh-cannulated hearts with KH buffer (KH-IRH). In addition, responses to dofetilide, flecainide, and diltiazem, were similar for C-IRH and KH-IRH hearts. Over the years (2006-2011), baseline data was collected from 79 hearts without cardioplegia and 100 hearts with cardioplegia (C-IRH; storage time 15 min), which showed no meaningful differences in a retrospective analysis. DISCUSSION: Cardiac function was preserved after cardioplegic treatment, however, coronary flow rates were decreased (-19.3%) in C-IRH hearts which indicated an altered coronary vascular tone. In conclusion, storage in cardioplegic solution preserves rabbit cardiac function, a practice that enables heart tissues to be collected at one site (e.g., vivarium) and transported to a laboratory in a separate location.

Comparison of Del Nido and Blood Cardioplegia in Pediatric Patients Undergoing Surgical Repair for Congenital Heart Disease.

The aim of the study is to investigate the impact of two different cardioplegia solutions, the del Nido (dN) and blood cardioplegia (BC), on postoperative troponin concentrations, vasoactive-inotrope score, and length of hospital stay in pediatric patients undergoing cardiovascular surgery for CHD. 80 subjects aged between 1 and 120 months who were scheduled for surgical repair for a CHD were prospectively enrolled in this study. Study subjects were allocated to one of the study groups using simple randomization technique as follows: The del Nido cardioplegia group (n = 40, median age 8.5 [5.5-14] months) and conventional blood cardioplegia group (n = 40, median age 11 [5-36] months). Aortic cross-clamp time and cardiopulmonary bypass time were recorded in all subjects. Troponin I and vasoactive-inotropic score, which indicates the amount of cardiovascular support by various inotropes or vasopressors, were recorded following the repair. The difference in troponin I, vasoactive-inotropic score (VIS), length of ICU stay, and length of hospital stay between the two groups was the primary outcome measure of this study. The volume of cardioplegia was significantly lower in dN group than that of the BC group (p < 0.001). Cardiopulmonary bypass time and aortic cross-clamp time were significantly shorter in subjects receiving dN cardioplegia than those receiving BC (p = 0.006, and p = 0.001, respectively). Subjects assigned to BC had higher Troponin I concentrations at postoperative 24th hour compared to subjects receiving dN cardioplegia [1.60 (0.92-2.49) ng/mL vs. 1.03 (0.55-1.83) ng/mL, p = 0.045]. VIS was also significantly higher in BC group at 24th [10 (10-13) vs. 10 (5-10), p = 0.032] and 48th hours [10 (1.5-10) vs. 0 (0-10), p = 0.005] compared to that of the dN cardioplegia group. The median extubation time was 7.5 (3.5-20.5) hours in dN cardioplegia group and 5 (4-10) hours in the BC group (p = 0.384). There were no significant differences between the groups with respect to the length of ICU stay and length of hospital stay. No mortality and no significant arrhythmias requiring medical or electrical cardioversion were noted in any of the groups. In conclusion, dN cardioplegia provides shorter aortic cross-clamp time and cardiopulmonary bypass time, and lower postoperative troponin I concentration and vasoactive-inotrope scores compared to BC in pediatric subjects undergoing surgical repair for CHD. However, lengths of ICU and hospital stay are similar in dN cardioplegia and BC groups.