Cardioplegic Solution Research Articles

Evaluating the need for magnesium administration following cardioplegic arrest with del Nido cardioplegia solution

Background: del Nido cardioplegia (dNC) solution is widely used in pediatric and congenital cardiac surgery. In 2014, Cincinnati Children’s Hospital Medical Center (CCHMC) changed from Mee cardioplegic solution to dNC. Since Mee solution does not contain magnesium, magnesium was administrated post cross-clamp removal, at a dose of 25mg/kg up to 1g, to abate hypomagnesemia. This practice remained in place with the use of dNC. We postulated that patients may experience hypermagnesemia under this protocol, possibly resulting in deleterious effects such as dysrhythmias and/or hypotension. Methods: To determine if exogenous magnesium is necessary post-clamp removal in our practice, a study examining magnesium levels during cardiopulmonary bypass (CPB) was completed from January 2022 through October 2023 (IRB #2021-0816). One hundred patients undergoing CPB with cross-clamp, ranging from infants to adults, were consented. Two magnesium samples were collected. Draw 1 (D1) was collected post cardioplegia administration and 30 minutes prior to cross-clamp removal. Draw 2 (D2) was collected post cross-clamp removal and 10 +/- 2 minutes following magnesium administration. Results: Both samples demonstrated magnesium levels >1.6mg/dl or higher (normal magnesium range at CCHMC, 1.6-2.6mg/dl). A Wilcoxon rank sum test demonstrated statistical significance for D1, comparing the number of samples which fell above 2.6 mg/dl vs. those that fell within the normal range (p<0.001). D2 demonstrated values above normal range for all but one sample, which does not satisfy the criteria of the Wilcoxon rank sum test for demonstrating significance (p=0.089); however, ninety-nine samples displayed hypermagnesemia. Conclusion: This study demonstrates that exogenous magnesium administration may not be necessary in the setting of our practice at CCHMC and dNC cardioplegic arrest.

Mitochondrial respiratory pathways in immature rat heart tissue using different cardioplegic solutions.

Minor defects in the mitochondrial ATP-generating system and post-cardioplegia oxidative phosphorylation can negatively impact cardiac function in immature hearts. This study aimed to examine the mitochondrial respiratory pathway using three different cardioplegic solutions (Custodiol HTK, St. Thomas, and Del Nido) during moderate (1h) and long (3h) ischemic periods. A total of 41 male Wistar albino rats were utilized in this study. Five experiments were conducted without the use of any cardioplegic solution (CP0 group). To assess both moderate and prolonged ischemic periods, six experiments were carried out in each of the following groups: CP1 group (St. Thomas solution), CP2 group (Custodiol HTK solution), and CP3 group (Del Nido solution). After 1h, the highest mitochondrial respiration rate was observed in the CP3 group and the lowest in the CP1 group (p = 0.006). After adding ADP substrate, the highest mitochondrial ATP-production-coupled respiration was recorded in the CP3 group, which was similar to the control group CP0. After 3h, while evaluating the ratio between mitochondrial respiration ATP-production coupled and basal respiration, significant differences were found between CP1 group and CP3 group (p = 0.035), as well as between the CP1 and CP0 groups (p = 0.045). Additionally, by assessing the condition of the outer mitochondrial membrane using the Cyt C effect (Cyt/Phos [ADP]), significant differences were observed between the CP1 and CP3 group (p = 0.004), as well as between CP1 and CP0 groups (p = 0.003). Del Nido cardioplegic solution provided optimal mitochondrial protection under moderate and long myocardial ischemia conditions.

Procurement and Preservation of Neonatal Porcine Cardiac Tissue.

The porcine and human heart are remarkably similar in cardiac physiology and biochemistry. Translational research involving the porcine biomedical model is becoming increasingly applicable for the study of human cardiac function in health and disease. Presently, few protocols exist for collecting experimentally viable cardiac tissue from large animal models, particularly during neonatal maturation. To address this deficiency, we have developed a technique to procure and preserve ventricular tissue from neonatal piglets at day 3 (n=4) and day 30 (n=6) post-partum. Piglets were subjected to a strict sedation, anesthesia, and analgesia regimen. During surgery, cardiopulmonary indices of electrocardiogram, heart rate, systolic and diastolic blood pressure, respiration rate, peripheral O2 saturation, and end-tidal CO2 were monitored continuously to ensure normal cardiac function. Prior to cardiectomy, each heart was perfused with an intravenous administration of heparin (10 ml/kg) and ice-cold Custodiol HTK cardioplegia solution (10 ml/kg). After cardiac explantation, myocardial samples (dimensions: 1 x 1 x 1 cm) were dissected from the left and right ventricles and snap-frozen in liquid nitrogen. Analysis via SDS-PAGE and densitometry demonstrated that myofibrillar proteins are stable and undegraded. Western Blots showed full expression of protein. These results suggest that the detailed cardiac tissue procurement technique preserves the experimental viability of the cardiac tissue and prevents the degradation of myofibrillar proteins.

Risk of Postoperative Hypermagnesemia in Cardiopulmonary Bypass Assisted Cardiovascular Surgery.

Magnesium administration is a common practice in cardiovascular surgeries utilizing cardiopulmonary bypass (CPB). However, concerns persist regarding the risk of hypermagnesemia, particularly in patients with kidney dysfunction. This study aims to determine the incidence of postoperative hypermagnesemia in CPB-assisted cardiovascular surgeries and identify the associated risk factors. This was a retrospective cohort study conducted at a tertiary medical center. Data from adult patients undergoing open-heart surgery utilizing CPB between 2018 and 2020 were analyzed. Sociodemographic, perioperative, and clinical variables were collected from electronic medical records. Logistic regression was utilized to identify independent risk factors for hypermagnesemia. Of 278 patients analyzed, 53.2% developed postoperative hypermagnesemia (Mg ≥2.5 mg/dL). Mild hypermagnesemia (Mg 2.5-3.9 mg/dL) was most common, with no significant impact on clinical outcomes observed. Patients with hypermagnesemia were older, with higher comorbidity burdens and lower baseline estimated glomerular filtration rate (eGFR). Cardioplegic solutions with higher magnesium content and lower baseline eGFR were independently associated with hypermagnesemia (OR 64.3; 95% CI 12.9-501.1 and OR 1.3; 95% CI, 1.1-1.5 respectively). Notably, ultrafiltration on CPB was associated with low risk of hypermagnesemia (OR 0.4, 95% CI 0.1-1.0, P value 0.048). This study highlights the importance of mindful magnesium supplementation strategies in those with advanced kidney disease. Future large-scale prospective multicenter studies should validate these findings and explore the extended effects of hypermagnesemia on clinical outcomes in patients with advanced CKD undergoing CPB surgeries.

Comparison of De Ritis Rate for Del Nido Versus Blood Cardioplegia in Patients Who Underwent Coronary Artery Bypass Graft Under Cardiopulmonary Bypass

Aim: Within the scope of this research, we aimed to compare the liver function tests, liver enzymes and De Ritis ratio (AST/ALT) of patients given Del Nido cardioplegia and blood cardioplegia in coronary heart surgery. Methods: This retrospective study included a total of 80 patients who underwent CPB-guided coronary heart surgery (CABG) with 40 Del Nido cardioplegia solutions and 40 blood cardioplegia solutions. CPB-guided coronary heart surgery patients given Del Nido cardioplegia solution were determined as the first group (Group 1), and patients given blood cardioplegia were determined as the second group (Group 2). Results: Preoperative and postoperative aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, direct bilirubin, and gamma-glutamyl transferase (GGT) levels of the groups were similar (p

Recent advances in Del Nido cardioplegia: A comprehensive analysis of randomized clinical trials in adult cardiac surgery.

Del Nido cardioplegia (DNC) has extensively been used for pediatric population undergoing cardiac surgery. However, its use in adult cardiac surgeries have been limited thus, its benefits are not yet fully known. This analysis was performed to evaluate the impact of DNC versus any other type of cardioplegia in adult patients who are undergoing cardiac surgery. We systematically searched PubMed, Cochrane Library, and Scopus from database inception till March 2023, and moderate to high-quality randomized controlled trials were included which compared DNC to other cardioplegia. The primary outcome was postoperative stroke and/or transient ischemic attack (TIA). Secondary outcomes included spontaneous rhythm return, postoperative myocardial infarction, all-cause mortality, postoperative atrial fibrillation, defibrillation after coronary reperfusion, postoperative intra-aortic balloon pump, postoperative kidney injury, postoperative low cardiac output syndrome, inotropic support, cardiopulmonary bypass time, cross-clamp time, blood transfusion, cardioplegia volume, hospital stay, intensive care unit stay, mechanical ventilation stay, postoperative left ventricular ejection fraction, and cardiac markers. In this meta-analysis, 13 studies were included with a patient population of 2207. Stroke and/or TIA studies (risk ratio [RR]: 0.54, 95% CI [0.29, 1.00]) and all-cause mortality studies (RR: 1.30, 95% CI [0.66, 2.56]) were insignificant. From the secondary outcomes, spontaneous rhythm return (RR: 1.58, 95% CI [1.02, 2.45]), defibrillation after coronary reperfusion (RR: 0.49, 95% CI [0.30, 0.79]), inotropic support (RR: 0.70, 95% CI [0.57, 0.85]), composite risk of stroke and/or TIA and/or acute kidney injury and mortality (RR: 0.72, 95% CI [0.53, 0.99]), cross-clamp time (mean difference [MD]: -6.01, 95% CI [-11.14, -0.89]), blood transfusion (RR: 0.73, 95% CI [0.60, 0.90]), cardioplegia volume (MD: -537.17, 95% CI [-758.89, -315.45]), troponin T (MD: -1.71, 95% CI [-2.11, -1.32]), creatine phosphokinase-MB (MD: -2.96, 95% CI [-5.84, -0.07]) were significant. Whereas all other secondary outcomes were found to be insignificant. No significant difference was observed between patients undergoing Del Nido administration in comparison to other cardioplegia solutions for the primary outcome, stroke or/and TIA.

Abstract Tu113: Metabolomic Profile of Human End-Stage Ischemic Cardiomyopathy Reveals Few Differences from Non-Ischemic Cardiomyopathy

Background: The heart is highly metabolic, relying on a range of fuels to sustain its high generation of ATP. The primary source of energy in the human heart is fatty acids, but fatty acid oxidation is reduced in failing hearts, contributing to a decrease in ATP production. Previously, we provided a comprehensive metabolic profile of human non-ischemic cardiomyopathy (NICM) hearts, including maintained ATP levels despite decreased energy charge (EC), lower acylcarnitines, acyl CoAs, and free fatty acids, suggesting a defect in fatty acid import. Research Questions: The pathogenesis of ischemic cardiomyopathy (ICM) is dramatically different from that of NICM, raising the question of whether metabolic defects differ between these two conditions. Aims: Our current study was therefore aimed at elucidating the metabolomic profile of end-stage ICM compared to that of NICM. Methods: Whole human hearts were obtained either from patients with end-stage heart failure (NICM or ICM) undergoing cardiac transplantation or from brain-dead organ donors. Hearts were arrested in situ and kept in ice-cold cardioplegia solution at all times. Transmural tissue samples were obtained from left ventricular free wall, snap frozen, and extracted metabolites were quantified by liquid chromatography coupled with mass spectrometer. Results: The comparison of metabolomics data from non-failing (NF) control heart samples and NICM samples were consistent with our previous study, with marked decrease in acylcarnitines and increase in lysophosphatidylcholine. On the other hand, the metabolomics profiles of ICM and NICM samples were remarkably similar. Phenylacetylglutamine and trimethylamine N-oxide, both related to atherosclerotic disease risk, were statistically significantly higher in ICM samples compared to NICM samples. Conclusion(s): The human cardiac metabolome of end-stage ICM is nearly identical to that of NICM, despite dramatically different pathogeneses, suggesting that end-stage heart failure constitutes a final common pathway. It would be of great interest to evaluate metabolomic profiles of the diseases differ at earlier timepoints.

Celsior® vs. St Thomas® cardioplegia: analysis of myocardial protection and clinical safety in neonates.

To compare the effectiveness and safety of Celsior® crystalloid solution to St Thomas® solution as cardioplegia in pediatric arterial switch surgery. A retrospective study was conducted on 180 patients who underwent arterial switch operation (ASO) between 2005 and 2019. The patients were divided into two groups: the St Thomas group receiving St Thomas solution and the Celsior® group receiving Celsior® solution. The study aimed to assess myocardial protection while evaluating clinical outcomes of patients between groups. Baseline characteristics not different between groups. The postoperative troponin release trends and blood lactate levels were not different between groups. However, the Celsior® group had a significant lower incidence of delayed sternal closure (9.7% vs. 19.5%; p = 0.09) and mechanical circulatory support (ECMO) (4.9% vs. 24.7%; p < 0.001) compared to the St Thomas group. The length of stay in the intensive care unit (ICU) was significantly shorter in the Celsior® group (4.6 ± 3.36 days vs. 8.72 ± 5.08 days, respectively; p < 0.001). There was no significant difference in 30-day mortality between the two groups (2.9% vs. 2.6%; p = 0.147). The study suggests that Celsior® solution is effective and safe for myocardial protection in pediatric arterial switch surgery. It may offer potential benefits such as reduced need for delayed sternal closure and ECMO support, as well as shorter ICU stay. However, the study has limitations including its retrospective design and the use of different cardioplegic solutions during different time periods. Further prospective randomized trials are needed for confirmation. ClinicalTrials.gov, ID: NCT04616222.

Gas-loaded nanocarriers to improve cardioprotection by cardioplegic solution

Gas-loaded nanocarriers to improve cardioprotection by cardioplegic solution

Comparison of a coronary bypass surgery using a combination of both on-pump beating heart and cardioplegic arrest with conventional coronary bypass surgery using cardioplegic arrest on-pump.

Antegrade cardioplegia may cause maldistribution in patients with multivessel coronary artery disease. Surgically bypassing large epicardial vessels before the cross-clamp and then administering cardioplegia from both the aortic root and the anastomosed grafts significantly prevent maldistribution and provide better cardiac protection. This study included 80 patients, all older than 70years with an ejection fraction between 25 and 35%. Patients were equally divided into two groups. Distal anastomoses to some of large epicardial coronary arteries were performed before the cross-clamp was placed. Grafted veins were attached to multi-perfusion set ports. Then, cross-clamping was performed, and the multi-perfusion set was disconnected from the aortic cannula and attached to the cardioplegia route. Antegrade cardioplegia was administered to both the aortic root and saphenous vein grafts. After all distal anastomoses were completed, the cross-clamp was removed, and the multi-perfusion set was connected to the aortic cannula again. Conventional coronary bypass techniques were used in group 2 patients. Inotropic agents were administered in 12 patients in group 1 and 29 patients in group 2 (p < 0.001). The average troponin I value in coronary sinus blood was 1.05 ± 0.8ng/mL in group 1 and 3.12 ± 0.7ng/mL in group 2 (p < 0.001). The average lactate value in coronary sinus blood was 1.15 ± 0.55mmol/L in group 1 and 3.7 ± 2.4mmol/L in group 2 (p < 0.001). Six patients died in the early postoperative period in group 2 (p = 0.028). The current technique considerably reduces cross-clamping time and allows better distribution of the cardioplegic solution, preserving myocardium. Reduced coronary sinus lactate and troponin I levels also indicate better myocardial protection.

Enhancing Heart Transplantation: Utilizing Gas-Loaded Nanocarriers to Mitigate Cold/Hypoxia Stress.

Gas-loaded nanocarriers (G-LN) show promise in improving heart transplantation (HTx) outcomes. Given their success in reducing cell death during normothermic hypoxia/reoxygenation (H/R) in vitro, we tested their integration into cardioplegic solutions and static cold storage (SCS) during simulated HTx. Wistar rat hearts underwent four hours of SCS with four G-LN variants: O2- or N2-cyclic-nigerosyl-nigerose-nanomonomers (CNN), and O2- or N2-cyclic-nigerosyl-nigerose-nanosponges (CNN-NS). We monitored physiological-hemodynamic parameters and molecular markers during reperfusion to assess cell damage/protection. Hearts treated with nanomonomers (N2-CNN or O2-CNN) showed improvements in left ventricular developed pressure (LVDP) and a trend towards faster recovery of the rate pressure product (RPP) compared to controls. However, nanosponges (N2-CNN-NS or O2-CNN-NS) did not show similar improvements. None of the groups exhibited an increase in diastolic left ventricular pressure (contracture index) during reperfusion. Redox markers and apoptosis/autophagy pathways indicated an increase in Beclin 1 for O2-CNN and in p22phox for N2-CNN, suggesting alterations in autophagy and the redox environment during late reperfusion, which might explain the gradual decline in heart performance. The study highlights the potential of nanomonomers to improve early cardiac performance and mitigate cold/H/R-induced stunning in HTx. These early improvements suggest a promising avenue for increasing HTx success. Nevertheless, further research and optimization are needed before clinical application.

Traditional vs. modified Ringer lactate-based del Nido cardioplegia impacts on clinical outcomes in patients undergoing coronary artery bypass grafting: results from a clinical trial

Introduction: myocardial protection with cardioplegia solution is one of the precautions during coronary bypass grafting surgery (CABG) with cardiopulmonary bypass (CPB) to reduce myocardial damage and ischemia/reperfusion injuries. Unfortunately, the major component of the del Nido cardioplegia solution, Plasma-Lyte A, is unreachable in Iran due to high cost. Therefore, we have utilized lactate Ringer's solution as the base solution for our modified del Nido solution (LR DN). Study design and methods: the present clinical trial was performed on 18-75 year old patients (EF&gt;35%) undergoing CABG with CPB in Imam Hossein hospital Tehran-Iran in 2021. Patients were randomly allocated to LR DN (modified del Nido cardioplegia) and PL DN (standard del Nido cardioplegia solution) groups. Serum level of cardiac troponin I (cTnI) at baseline, declamp, ICU admission, and 24 hours after admission, the type and dosage of inotrope agents, EF, rate of arrhythmia after clamp removal and lactate level were measured and compared between groups. Results: 109 patients were recruited. There were no statistically significant differences between the PL DN cardioplegia and LR DN groups for cardiopulmonary bypass times, cardiac enzymes, transfusion requirements, and arterial blood gases. However, postoperative serum levels of cTnI among patients in the LR DN group was significantly higher than patients of the PL DN group after ICU admission and 24 hours postoperatively. Also, more patients needed epinephrine administration in the operating room in the LR DN group (29.8% vs. 11.5%; p: 0.019 vs. PL DN group). Conclusion: we concluded that standard del Nido cardioplegia solution offers better myocardial protection compared with Ringer's lactate-based del Nido cardioplegia in adult patients undergoing CABG with CPB. We recommend using standard del Nido cardioplegia with a base of Plasma-Lyte A for patients presenting for CABG surgery.

Association between Aquaporin 7 Expression and Myocardial Protection with Nicorandil or Del Nido Cardioplegia: An Experimental Study

Background: Aquaporin 7 (AQP7), a member the aquaglyceroporin subgroup of the AQP family, is a water channel that controls transport of glycerol and water in heart tissues. It facilitates the uptake of glycerol, a substrate for cardiac energy production, in cardiomyocytes. St. Thomas' Hospital cardioplegic solution No. 2 has cardio-protective effect even in AQP7-deficient hearts. Here, we aimed to determine whether nicorandil or del Nido cardioplegia (DNC) solution can protect AQP7-deficient hearts. Methods: The hearts of male AQP7 knockout (KO) and wild-type (WT) C57/B6N mice (age &gt;15 weeks) were aerobically perfused using the Langendorff technique, and cardiac function was measured as left ventricular diastolic pressure (LVDP) throughout the study. Troponin T was measured as an indicator of myocardial damage after reperfusion for 60 min. We compared WT and KO controls subjected to 25 min of global ischemia as well as WT and KO groups infused with nicorandil (100 µM) for 10 min followed by 25 min of global ischemia. We also compared WT-DNC and KO-DNC hearts administered with DNC for 2 min followed by 23 min of global ischemia (Study 2). Results: The final recovery rates of LVDP were 20.8 ± 7.0%, 28.1 ± 7.6%, 40.0 ± 8.4%, and 38.7 ± 4.7% in the WT control, KO control, WT nicorandil, and KO nicorandil groups, respectively. The LVDP recovered faster in the hearts treated with DNC and reached a significantly higher plateau in the KO than in the WT hearts. Troponin T values were 2144 ± 493 and 1313 ± 717 in the WT and KO groups, respectively (p = 0.041). Conclusion: The Langendorff perfusion model revealed similar myocardial protective effects of nicorandil in AQP7-deficient mice as in WT mice. AQP7 deficiency did not impair the cardioprotective effects of DNC solution.

Del nido cardioplegia in adults: a retrospective observational study in comparison to modified St. Thomas cardioplegia in cardiac surgery

BackgroundSt. Thomas cardioplegia is commonly administered to adults, yet repeated dosing at brief intervals is required. Del Nido’s cardioplegic solution provides a prolonged duration of safe myocardial arrest, yet it was primarily intended for pediatric cardiac surgery. Recently, there has been an increasing interest in using Del Nido’s in adults; this might be due to its ease of administration and extended re-dosing intervals. This study contrasted Del Nido’s to modified St. Thomas cardioplegia in adults.MethodsThis study was conducted on 200 patients. Troponin-T was the primary outcome within the first 24 and 48 h post-surgery. Cardiopulmonary bypass time, cross-clamp time, intraoperative use of inotropic support, defibrillator and/or intra-aortic balloon were the secondary outcomes of the study.ResultsThere was a significant reduction in post-operative Troponin-T levels in the first 24 and 48 h within Del Nido’s group compared to the modified St. Thomas group. The cross-clamp and cardiopulmonary bypass times were also found to be lower within Del Nido’s group.ConclusionThis study has demonstrated a significant reduction in early postoperative Troponin-T levels as well as operative times favoring Del Nido’s in adults.

Blood cardioplegia reduces intraoperative ventricular fibrillation and transfusion requirements compared to crystalloid cardioplegia in canine mitral valve repair.

Cardioplegic solutions are indispensable for open-heart surgeries, including mitral valve repair (MVR), a potentially curative treatment for myxomatous mitral valve disease in dogs. However, procedural methodologies are not fully established, and complications are yet to be comprehensively understood. Cardioplegic solutions contain various substances to protect the myocardium under temporal cardiac arrest. Nevertheless, ventricular fibrillation (VF) occurs as a common complication after releasing the crossclamp. Based on these backgrounds, the search for optimal cardioplegic solutions in dogs undergoing MVR is an urgent issue. This study aims to evaluate the occurrence of VF in dogs treated with blood cardioplegia (BCP) versus crystalloid cardioplegia (CCP) during MVR. A total of 251 client-owned dogs who underwent MVR from November 2015 to November 2017 were included. We retrospectively assessed the relationship between VF and type of cardioplegia (CCP or BCP) based on surgical records, including VF incidence, transfusion use, crossclamp time, and echocardiographic measurements. Logistic regression analysis showed that the CCP group was associated with the occurrence of VF (OR, 2.378; CI, 1.133-4.992; P = .022). In addition, the CCP group was associated with transfusion use (OR, 2.586; CI, 1.232-5.428, P = .022). There was no difference between the groups for the pre- and postoperative echocardiographic measurements. The BCP group had a lower incidence of VF and less transfusion use than the CCP group. This finding indicates that BCP may be a superior cardioplegic technique for MVR in dogs.

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

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. 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. 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). 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.

Cirbp suppression compromises DHODH-mediated ferroptosis defense and attenuates hypothermic cardioprotection in an aged donor transplantation model.

Hypothermia is commonly used to protect donor hearts during transplantation. However, patients transplanted with aged donor hearts still have severe myocardial injury and decreased survival rates, but the underlying mechanism remains unknown. Because aged hearts are not considered suitable for donation, the number of patients awaiting heart transplants is increasing. In this study, we examined whether hypothermic cardioprotection was attenuated in aged donor hearts during transplantation and evaluated potential therapeutic targets. Using a rat heart transplantation model, we found that hypothermic cardioprotection was impaired in aged donor hearts but preserved in young donor hearts. RNA-Seq showed that cold-inducible RNA-binding protein (Cirbp) expression was decreased in aged donor hearts, and these hearts showed severe ferroptosis after transplantation. The young donor hearts from Cirbp-KO rats exhibited attenuated hypothermic cardioprotection, but Cirbp overexpression in aged donor hearts ameliorated hypothermic cardioprotection. Cardiac proteomes revealed that dihydroorotate dehydrogenase (DHODH) expression was significantly decreased in Cirbp-KO donor hearts during transplantation. Consequently, DHODH-mediated ubiquinone reduction was compromised, thereby exacerbating cardiac lipid peroxidation and triggering ferroptosis after transplantation. A cardioplegic solution supplemented with CIRBP agonists improved hypothermic cardioprotection in aged donor hearts, indicating that this method has the potential to broaden the indications for using aged donor hearts in transplantation.

Myocardial protection in pediatric cardiac surgery - deep look to the most often used cardioplegic solutions

Myocardial protection in pediatric cardiac surgery - deep look to the most often used cardioplegic solutions

Efficacy of propofol-supplemented cardioplegia on biomarkers of organ injury in patients having cardiac surgery using cardiopulmonary bypass: a statistical analysis plan for the ProMPT-2 randomised controlled trial

BackgroundThe ProMPT-2 trial (Propofol for Myocardial Protection Trial #2) aims to compare the safety and efficacy of low- and high-dose propofol supplementation of the cardioplegia solution during adult cardiac surgery versus sham supplementation. This update presents the statistical analysis plan, detailing how the trial data will be analysed and presented. Outlined analyses are in line with the Consolidated Standards of Reporting Trials and the statistical analysis plan has been written prior to database lock and the final analysis of trial data to avoid reporting bias (following recommendations from the International Conference on Harmonisation of Good Clinical Practice).Methods/designProMPT-2 is a multi-centre, blinded, parallel three-group randomised controlled trial aiming to recruit 240 participants from UK cardiac surgery centres to either sham cardioplegia supplementation, low dose (6 µg/ml) or high dose (12 µg/ml) propofol cardioplegia supplementation. The primary outcome is cardiac-specific troponin T levels (a biomarker of cardiac injury) measured during the first 48 h following surgery.The statistical analysis plan describes the planned analyses of the trial primary and secondary outcomes in detail, including approaches to deal with missing data, multiple testing, violation of model assumptions, withdrawals from the trial, non-adherence with the treatment and other protocol deviations. It also outlines the planned sensitivity analyses and exploratory analyses to be performed.DiscussionThis manuscript prospectively describes, prior to the completion of data collection and database lock, the analyses to be undertaken for the ProMPT-2 trial to reduce risk of reporting and data-driven analyses.Trial registrationISRCTN ISRCTN15255199. Registered on 26 March 2019.

Modified del Nido cardioplegia is associated with low incidence of low main strong ion difference and hyperchloremia in pediatric patients after cardiac surgery.

The aims of this study were (1) to determine the associations of cardioplegic solutions with postoperative main strong ion difference (mSID), which is the difference between sodium ion concentration and chloride ion concentration([Cl-]) and (2) to determine the associations of cardioplegic solutions with markers of organ dysfunction. In this retrospective cohort study, patients aged <5years who underwent cardiac surgery in a tertiary teaching hospital were included. Patients were classified on the basis of the type of cardioplegic solution: modified del Nido cardioplegia (mDNC) and conventional cardioplegia (CC). The effects of mDNC on postoperative mSID and markers of organ functions were examined using propensity-matched analysis. A total of 500 cases were included. mDNC solution was used in 163 patients (32.6%). After propensity score matching, patients in the mDNC group (n=152) had significantly higher minimum mSID [28 (26, 30) mEq/L vs. 27 (25, 29) mEq/L, p=0.02] and lower maximum [Cl-] [112 (109, 114) mEq/L vs. 113 (111, 117) mEq/L, p<0.001] than patients in the CC group (n=304). The incidences of low mSID and hyperchloremia in the mDNC group were significantly lower than those in the CC group (63.8 vs. 75.7%, p=0.01 and 63.2 vs. 79.3%, p<0.001, respectively). There was no significant difference in the incidence of postoperative acute kidney injury and B-type natriuretic peptide level between the two groups. The use of modified del Nido cardioplegia may reduce the incidence of abnormal mSID and hyperchloremia compared with the use of a chloride-rich cardioplegic solution.