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The present study aimed the functional recovery evaluation after long term of cardiac arrest induced by Custodiol (crystalloid-based) versus del Nido (blood-based) solutions, both added lidocaine and pinacidil as cardioplegic agents. Experiments were performed in isolated rat heart perfusion models. Male rat heart perfusions, according to Langendorff technique, were induced to cause 3 hours of cardiac arrest with a single dose. The hearts were assigned to one of the following three groups: (I) control; (II) Custodiol-LP; and (III) del Nido-LP. They were evaluated after ischemia throughout 90 minutes of reperfusion. Left ventricular contractility function was reported as percentage of recovery, expressed by developed pressure, maximum dP/dt, minimum dP/dt, and rate pressure product variables. In addition, coronary resistance and myocardial injury marker by alpha-fodrin degradation were also evaluated. At 90 minutes of reperfusion, both solutions had superior left ventricular contractile recovery function than the control group. Del Nido-LP was superior to Custodiol-LP in maximum dP/dt (46%±8 vs. 67%±7, P<0.05) and minimum dP/dt (31%±4 vs. 51%±9, P<0.05) variables. Coronary resistance was lower in del Nido-LP group than in Custodiol-LP (395%±50 vs. 307%±13, P<0.05), as well as alpha-fodrin degradation, with lower levels in del Nido-LP group (P<0.05). Del Nido-LP cardioplegia showed higher functional recovery after 3 hours of ischemia. The analysis of alpha-fodrin degradation showed del Nido-LP solution provided greater protection against myocardial ischemia and reperfusion (IR) in this experimental model.

This study aimed to evaluate the safety and efficacy of a modified, bloodless Del Nido (DN) cardioplegia solution in patients undergoing isolated aortic valve replacement (AVR). A total of 370 patients who underwent isolated AVR between 2015 and 2022 were retrospectively analyzed. Patients were categorized into two groups based on the cardioplegia solution used: the bloodless DN group (N = 180) and the histidine-tryptophan-ketoglutarate (HTK) group (N = 190). To reduce selection bias and adjust for baseline differences, inverse probability of treatment weighting analysis was performed. There was no significant difference in in-hospital mortality between the two groups (HTK vs. DN: 1.2% vs. 0.9%, P = 0.554). However, the rate of spontaneous sinus rhythm restoration without the need for defibrillation following aortic cross-clamp release was significantly higher in the DN group (40.0% vs. 75.2%, P < 0.001). Additionally, the initial postoperative lactate level (3.0 ± 2.6 mmol/L vs. 2.2 ± 1.4 mmol/L, P = 0.002), and the incidence of low cardiac output syndrome (9.4% vs. 1.7%, P < 0.001) were significantly lower in the DN group compared to the HTK group. Other postoperative morbidities did not differ significantly between the groups. The modified bloodless Del Nido cardioplegia demonstrated favorable myocardial protection and early clinical outcomes compared to HTK solution in patients undergoing isolated AVR. These findings suggest that the bloodless Del Nido technique may be a viable alternative, although further validation in larger, prospective studies is warranted.

Perioperative cardiac xenograft dysfunction (PCXD) describes a rapidly developing loss of cardiac function after xenotransplantation. PCXD occurs despite genetic modifications to increase compatibility of the heart. We report on the incidence of PCXD using static preservation in ice slush following crystalloid or blood-based cardioplegia versus continuous cold perfusion with XVIVO heart solution (XHS) based cardioplegia. Baboons were weight matched to genetically engineered swine heart donors. Cardioplegia volume was 30 cc/kg by donor weight, with del Nido cardioplegia and the addition of 25% by volume of donor whole blood. Continuous perfusion was performed using an XVIVO Perfusion system with XHS to which baboon RBCs were added. PCXD was observed in 5/8 that were preserved with crystalloid cardioplegia followed by traditional cold, static storage on ice. By comparison, when blood cardioplegia was used followed by cold, static storage, PCXD occurred in 1/3 hearts and only in 1/5 hearts that were induced with XHS blood cardioplegia followed by continuous perfusion. Survival averaged 17 hours in those with traditional preservation and storage, followed by 11.47 days and 15.03 days using blood cardioplegia and XHS+continuous preservation, respectively. Traditional preservation resulted in more inotropic support and higher average peak serum lactate 14.3±1.7 mmol/L compared to blood cardioplegia 3.6±3.0 mmol/L and continuous perfusion 3.5±1.5 mmol/L. Blood cardioplegia induction, alone or followed by XHS perfusion storage, reduced the incidence of PCXD and improved graft function and survival, relative to traditional crystalloid cardioplegia-slush storage alone.

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.

Background and Objectives: The majority of cardiac surgical procedures are performed using cardiopulmonary bypass and cardioplegia-induced cardiac arrest. Cardiac arrest and reperfusion may lead to ischemia-reperfusion injury of the myocardium. The aim of this study was to investigate whether gradual reperfusion with a slow increase in oxygen partial pressure leads to a reduction in reperfusion injury. Materials and Methods: Fifty patients undergoing elective cardiac surgery were included in this prospective randomized study. Patients in the hyperoxemic (control) group received conventional reoxygenation (paO2 250–300 mmHg). Patients in the normoxemic (study) group received gradual reoxygenation (1st-minute venous blood with paO2 30–40 mmHg, 2nd-minute arterial blood with paO2 100–150 mmHg). Periprocedural blood samples were taken serially, and markers of myocardial injury were analyzed. In addition, the influence of gradual reoxygenation on hemodynamics, inflammation, and the overall perioperative course was evaluated. Results: There was a trend toward higher CK levels in the hyperoxemia group without statistical significance; however, CK-MB and troponin T levels did not show any statistical difference between the two groups. Potassium concentrations in the coronary sinus were significantly higher in the hyperoxemia group at 3 and 8 min after opening of the aortic cross-clamp (6.88 ± 0.87 mmol/L vs. 6.30 ± 0.91 mmol/L and 5.87 ± 0.73 mmol/L vs. 5.43 ± 0.42 mmol/L, respectively; p = 0.03 and p = 0.02). All other measurements did not show a statistical difference between the two groups. Conclusions: The use of gradual reperfusion in cardiac surgery with cardiopulmonary bypass and cardiac arrest is safe. However, it does not reduce ischemia-reperfusion injury compared to standard hyperoxemic reperfusion.

Background:Remote ischaemic preconditioning (RIPC) induced by brief ischaemia and reperfusion of the arm reduces myocardial injury in coronary artery bypass (CABG) surgery patients receiving predominantly cross-clamp fibrillation for myocardial protection. However, cold-blood cardioplegia is the more commonly used method world wide.Objective:To assess whether RIPC is cardioprotective in CABG patients receiving cold-blood cardioplegia.Design:Single-centre, single-blinded, randomised controlled trial.Setting:Tertiary referral hospital in London.Patients:Adults patients (18–80 years) undergoing elective CABG surgery with or without concomitant aortic valve surgery with cold-blood cardioplegia. Patients with diabetes, renal failure (serum creatinine >130 mmol/l), hepatic or pulmonary disease, unstable angina or myocardial infarction within the past 4 weeks were excluded.Interventions:Patients were randomised to receive either RIPC (n = 23) or control (n = 22) after anaesthesia. RIPC comprised three 5 min cycles of right forearm ischaemia, induced by inflating a blood pressure cuff on the upper arm to 200 mm Hg, with an intervening 5 min reperfusion. The control group had a deflated cuff placed on the upper arm for 30 min.Main outcome measures:Serum troponin T was measured preoperatively and at 6, 12, 24, 48 and 72 h after surgery and the area under the curve (AUC at 72 h) calculated.Results:RIPC reduced absolute serum troponin T release by 42.4% (mean (SD) AUC at 72 h: 31.53 (24.04) μg/l.72 h in controls vs 18.16 (6.67) μg/l.72 h in RIPC; 95% CI 2.4 to 24.3; p = 0.019).Conclusions:Remote ischaemic preconditioning induced by brief ischaemia and reperfusion of the arm reduces myocardial injury in CABG surgery patients undergoing cold-blood cardioplegia, making this non-invasive cardioprotective technique widely applicable clinically.Trial registration number:NCT00397163.

Acute kidney injury (AKI) is a serious complication following on-pump cardiac surgery. Choosing the cardioplegic solution with the most appropriate myocardial protection and lowest grade of AKI could improve patient outcome. We compared the crystalloid histidine-tryptophan-ketoglutarate (HTK) solution and a Jonosteril -based DelNido blood cardioplegic solution regarding AKI in a porcine model. Therefore, German landrace pigs (50-60kg) underwent median sternotomy, cardiopulmonary bypass at 34 °C and 90 min of cardiac arrest. Animals were randomized to single-shot cardioplegia of HTK (  = 9) or DelNido (  = 9) cardioplegic solution followed by 120 min of reperfusion. This study demonstrated that DelNido cardioplegia induced less hemoglobin (  < 0.01) and electrolyte imbalances of blood sodium, chloride, and calcium levels (all  < 0.01) after aortic cross-clamp than HTK cardioplegia. Renal biopsy analysis after 120 min of reperfusion revealed that histomorphological changes, oxidative and nitrosative stress as well as the cytosolic release of pro-apoptotic molecules in different nephron structures were comparable in HTK and DelNido cardioplegia. The comparability of both cardioplegic solutions was supported by measurements of the urine AKI biomarkers of L-type fatty acid-binding protein 1 (  = 0.38), neutrophil gelatinase-associated lipocalin (  = 0.34), and cystatin C (  = 0.46), which could not detect any differences between the groups. This large animal study demonstrated superiority of the DelNido solution regarding hemoglobin and blood electrolyte concentrations, but comparability of the HTK and DelNido blood cardioplegic solution regarding AKI for surgical interventions requiring cardiac arrest of 90 min. Patients with a higher risk for adverse events, due to either complex, prolonged surgery or a multitude of comorbidities, could especially benefit from the more physiological arrest conditions with DelNido cardioplegia.

ABSTRACT Del Nido cardioplegia (DNC), a blood‐and‐crystalloid solution containing high and low concentrations of potassium and calcium, respectively, is used as a single‐dose antegrade infusion to induce immediate cardiac arrest in the surgery of patients with cardiovascular diseases requiring extracorporeal circulation. Adding cardioprotective molecules may further reduce the damage‐triggered ischemia/reperfusion (I/R) injury. Angiotensin‐(1–9) (Ang‐(1–9)) and angiotensin‐(1–7) (Ang‐(1–7)), members of the counter‐regulatory renin‐angiotensin system, have shown cardioprotective effects in cardiac hypertrophy and I/R models. This study aimed to evaluate the effects of Ang‐(1–9) and Ang‐(1–7), as adjuvants of the DNC, on cardioprotection and ventricular function in isolated rat hearts subjected to I/R and in cultured neonatal rat ventricular myocytes subjected to simulated I/R (sI/R). The addition of DNC and Ang‐(1–9) and Ang‐(1–7) decreased lactic dehydrogenase (LDH) release in cultured cardiomyocytes subjected to sI/R in comparison to those cardiomyocytes subjected to sI/R and incubated with DNC alone. Moreover, hearts treated with Ang‐(1–9) during reperfusion after DNC + I/R exhibited fewer arrhythmias and required less time to reach left ventricular developed pressure stability. Overall, reperfusion with DNC and Ang‐(1–9) improves the recovery of the left ventricular function of the heart.

A variety of cardioplegia techniques with different components are implemented to ensure myocardial protection, in addition to keeping the operationa field immobile and free of blood during cardiac surgery. The implemented cardioplegia has unwanted negative effects on other end organs. In this study, our aim was to compare the effects of Del Nido cardioplegia and blood cardioplegia solutions on postoperative intensive care duration, drainage, and renal functions for patients undergoing cardiopulmonary bypass and bypass graft operations. Selections were made from patients undergoing elective bypass graft operations in our clinic from January 1, 2022 to December 31, 2023. Patients were randomly selected, retrospectively assessed, and divided into two groups - De Nido group (Group 1) and blood cardioplegia group (Group 2). Comparisons were made between these groups in terms of intensive care duration, drainage, and renal functions. The study included 120 patients. The Del Nido cardioplegia group included 60 patients, with 60 patients in the blood cardioplegia group. Comparisons between the groups found that the aortic cross-clamping duration was significantly high in Group 1 (P = 0.014). The noradrenaline dose given to Group 1 was high (P = 0.004). In terms of renal injury, significant degree of elevation was present in Group 1 (P = 0.027). The longer aortic cross-clamping duration in Group 1 may be assessed as a determinant factor for noradrenaline dose and acute kidney injury. This study concluded that it willbe appropriate to choose the cardioplegia method by performing broader meta-analysis studies and minimizing limiting factors.