Crystalloid Cardioplegic Solution Research Articles

Optimizing Cardioplegic Solutions: A Focus on Pharmaco-Cold Strategies

This study investigates the impact of crystalloid cardioplegic solutions (CCS) on electrophysiological mechanisms and the contractile system during the diastolic phase. Extracellular solutions, categorized by ion concentration, demonstrate efficacy in inducing cardiac arrest through moderately elevated potassium or potassium-magnesium combinations, aligning with normal or slightly reduced sodium and calcium levels. Notably, the ease of equilibration with myocardial tissue enhances the protective effect, correlating with infusion volume and duration of action. However, drawbacks such as low buffering capacity and the need for reinfusion after 15-20 minutes are identified. This research sheds light on the dynamic relationship between solution composition, duration of action, and protective efficacy, providing valuable insights for refining cardioplegic protocols in cardiac surgeries. Highlights: Intracellular vs. Extracellular Impact: Explore ion concentration's influence on crystalloid cardioplegic solutions, emphasizing the choice between intracellular and extracellular formulations. Equilibration Dynamics: Investigate the direct correlation between infusion volume, duration of action, and the protective effect, emphasizing equilibration with myocardial tissue. Refining Cardioplegic Protocols: Identify limitations like low buffering capacity, necessitating reinfusion, and offer insights into strategies for enhancing cardioplegic protocols in cardiac surgeries. Keywords: Cardioplegia, Intracellular Solutions, Calcium paradox, Protective Efficacy, Cellular Metabolism

Comparative study between conventional crystalloid cardioplegic solution with modified del nido cardioplegia in mitral valve regurgitation surgery

Background: Cardioplegia is crucial for protecting the heart. Long-term cardiac protection is offered by the Del Nido Cardioplegia solution (dNCS). Aim: To compare conventional crystalloid cardioplegia with modified del Nido cardioplegia in mitral valve regurgitation replacement surgery. Objectives and Methods: This randomized clinical study included 80 patients undergoing to elective mitral regurgitation replacement surgery of both sex and age from 21 to 60 years with ASA (III and IV). All 80 patients were randomly assigned to receive conventional cardioplegia (St. Thomas’ cardioplegic solutions) or to obtain a modified del Nido cardioplegia (using normal saline) (groups A and B, respectively). The laboratory data for assessment of myocardial protection were obtained through measurements of preoperative serum levels of cardiac enzymes as, CK-MB, troponin, and lactate, immediately after operation, 12 and 24 hours postoperatively. Results: There was a significant increase in CK-MB only after 1 h (p < .001) in group (A) and after 12 h. CK-MB and lactate levels were significantly increased (p < 0.05). Also, after 24 h. CK-MB and Troponin T levels were significantly increased (p < .001). Regarding complications, one patient had atrial fibrillation and one case had permanent stroke in group (A), and two patients died in group (A), while one patient died in group (B) without a significant difference between the groups. Conclusions: We report that Modified Del Nido Cardioplegia has better postoperative chemical parameters as CK-MB, Troponin T and Lactate in mitral valve surgery in adults. DNC is a safe alternative to conventional cardioplegia and has achieved at least the same results.

Minimal Extracorporeal Circulation and Microplegia in the Setting of Urgent Coronary Artery Bypass Grafting.

We aimed to analyse the performance of minimal invasive extracorporeal circulation (MiECC) concomitantly with Microplegia, in patients with recent myocardial infarction (MI) undergoing urgent coronary artery bypass grafting (CABG) surgery. We included patients with a recent MI (≤7 days) undergoing isolated CABG surgery using MiECC. The primary endpoint was a major cardiovascular or cerebrovascular event (MACCE). In a secondary analysis, we compared our institutional Microplegia concept with the use of a crystalloid single-shot cardioplegic solution. In total, 139 patients (mean ± standard deviation (SD) age 66 ± 10 years) underwent urgent CABG surgery using Microplegia; 55% (n = 77) of the patients had an acute MI within 1-7 days preoperatively; 20% (n = 28) had an acute MI within 6-24 h; and 24% (n = 34) had an acute MI within <6 h preoperatively. The number of distal anastomoses was a geometric mean of 4 (95% confidence interval 3-4). The MACCE and in-hospital mortality were 7% (n = 10) and 1% (n = 2), respectively. The results were confirmed in a secondary analysis comparing Microplegia with crystalloid cardioplegic solution (n = 271). The use of MiECC with Microplegia in urgent CABG surgery is feasible and safe and provides a straight-forward intraoperative setting. Therefore, it can also be considered to retain the benefits of MiECC in urgent CABG surgery.

The Use of Blood and Crystalloid Cardioplegia in Adult Open-Heart Surgery on Postsurgical Outcomes

Abstract Background: Myocardial ischemia can occur due to hypotension, shock, coronary heart disease, and aortic cross-clamping during open-heart surgery using a cardiopulmonary bypass machine. As the cardioprotective method, cardioplegia is classified into blood or crystalloid base. This systematic review is aimed to describe the effectiveness of blood and crystalloid cardioplegic solutions in adult open-heart surgery procedures by focusing on their effects on cardiac enzymes. Materials and Methods: This study investigated the effect of blood and crystalloid cardioplegia on troponin (cTn) and creatinine kinase myocardial bound. The literature search was carried out on several Cochrane, PubMed, PMC, and Google Scholar databases from January 2014 to August 2020 using the MeSH keywords and Boolean operator. Results: We obtained 346 articles and identified six prospective randomized studies from four countries. The majority discussed the comparison of blood cardioplegia and crystalloids in coronary revascularization cardiac surgery (coronary artery bypass grafting). Overall, the articles used have a low risk of bias despite their high level of homogenicity. Conclusions: The current literatures on cardioplegia in adults do not provide adequate advanced-phase trials. Both types of cardioplegia provide a reasonable protection for myocardium. However, several studies reveal that crystalloid cardioplegia increases cardiac enzymes more significantly than blood cardioplegia. This research has been registered with PROSPERO with the number CRD42022312548.

Custodiol-HTK Solution Vs. Conventional Cardioplegia for Myocardial Protection During Coronary Artery Bypass Grafting Following Recent ST-Elevation Myocardial Infarction

Abstract Background: Histidine-tryptophan-ketoglutarate (HTK), Bretschneider's, or Custodiol is an intracellular crystalloid cardioplegic solution which is claimed to offer single shot cardioplegia for myocardial protection during complex cardiac procedures for up to 3 h. We aimed to compare the clinical outcome of early coronary artery bypass grafting (CABG) using blood cardioplegia vs. Custodiol solution for myocardial protection in patients with recent ST-elevation myocardial infarction (STEMI). Materials and Methods: This prospective comparative study included 100 patients with recent STEMI who underwent early CABG at our institution between January 2019 and December 2020. The patients were divided into two groups: group A (n = 50) received blood cardioplegia and group B (n = 50) received Custodiol-HTK crystalloid cardioplegia. Results: There were non-significant differences in postoperative mortality and complication rates between both the groups except for significantly higher proportion of post-operative arrythmias after Custodiol cardioplegia (26% vs. 8%, P = 0.01). Custodiol was associated with significantly lower levels of blood troponin and higher levels of blood lactate for 6 h after CABG. Custodiol results in significantly shorter durations of mechanical ventilation (11.98 ± 4.03 vs. 18.28 ± 8.84 h, P < 0.001) and intensive care unit (ICU) stay (70.04 ± 14.80 vs. 80.20 ± 19.91 h, P = 0.01), with non-significantly shorter duration of post-operative hospital stay (7.98 ± 2.76 vs. 9.24 ± 3.41 days, P = 0.06). Conclusion: Custodiol as a single shot without interruption of the operative technique offers shorter durations of mechanical ventilation and ICU stay than blood cardioplegia, with more acceptable levels of post-operative troponin in high-risk patients who underwent early CABG for recent STEMI.

Efficacy of Whole-Blood Del Nido Cardioplegia Compared with Diluted Del Nido Cardioplegia in Coronary Artery Bypass Grafting: A Retrospective Monocentric Analysis of Pakistan.

Background and Objectives: Cardioplegia is one of the most significant components used to protect the myocardium during cardiac surgery. There is a paucity of evidence regarding the utilization of whole-blood Del Nido cardioplegia (WB-DNC) on clinical outcomes in coronary artery bypass grafting (CABG). The purpose of this retrospective cross-sectional study is to compare the effectiveness of diluted (blood to crystalloid; 1:4) Del Nido cardioplegia (DNC) with WB-DNC in patients who underwent elective CABG in a tertiary care hospital in Lahore-Pakistan. Materials and Methods: This was a retrospective descriptive study conducted at the Department of Cardiovascular Surgery, King Edward Medical University, Lahore. The medical database of all consecutive patients admitted from January 2018 to March 2020 and who fulfilled the inclusion criteria were reviewed. Results: Out of 471 patients admitted during the study period, 450 underwent various elective cardiac surgeries. Out of 450, 321 patients (71.33%) were operated on for CABG. Only 234/321 (72.89%) CABG patients fulfilled our inclusion criteria; 120 (51.28%) patients received WB-DNC, while 114 (48.71%) patients were administered with DNC. The former group presented with better clinical outcomes compared with the latter in terms of lesser requirements of inotropic support, low degree of hemodilution, shorter in-hospital stay, improved renal function, and cost-effectiveness. Peak values of serum Troponin-T (Trop-T), creatine kinase-myocardial band (CK-MB) release, and activated clotting time (ACT) were also lower in the WB-DNC group compared with the DNC group. Conclusions: The WB-DNC conferred better myocardial protection, improved early clinical outcomes, and also proved to be economical for patients undergoing elective CABG compared with classical crystalloid cardioplegia solution.

Celsior® crystalloid cardioplegia versus standard hyperkalemic normothermic blood cardioplegia: Analysis of myocardial protection in elective mitral valve repair.

With the increase and refinement of video assisted mitral valve surgery, cristalloïd cardioplegia started regaining popularity. The aim of our study was to evaluate the effectiveness of Celsior®, a crystalloid cardioplegic solution, on myocardial protection in elective surgical mitral valve repair in comparison to blood based hyperkalemic cardioplegia. In this observational retrospective study, all consecutive elective isolated surgical mitral valve repair where Celsior® or normothermic hyperkalemic blood cardioplegia were used were included. Primary endpoint was any sign of myocardial protection failure (troponin levels, need for inotropic or mechanical support, rhythm disturbances, mortality). Secondary endpoint was Celsior® safety (allergic reactions, bleeding, organ toxicities). From January 2009 to August 2016, 382 patients underwent elective isolated mitral valve repair in whom normothermic hyperkalemic blood cardioplegia (n = 181) or Celsior® (n = 201) were used. There were no statistically significant differences in baseline characteristics including Euroscore 2. Peak troponin (pg/ml) release and 30-days mortality were not statistically different. Need for cardioversion was significantly more frequent in the Celsior® group (47% vs 13%, p < 0.001). There was no statistical difference in post-operative atrial fibrillation, permanent pacemaker implantation, reoperation for bleeding, transfusion, acute kidney injury, haemoglobin at discharge or length of stay. No allergic reaction to Celsior® occurred. Effective myocardial protection was achieved with the Celsior® cardioplegic solution with no unexpected toxicity. Celsior® may be an efficacious and safe cardioprotective strategy in mitral valve repair.

Cardiac surgery in acute myocardial infarction: crystalloid versus blood cardioplegia \u2013 an experimental study

BackgroundBecause hearts in acute myocardial infarction are often prone to ischemia-reperfusion damage during cardiac surgery, we investigated the influence of intracellular crystalloid cardioplegia solution (CCP) and extracellular blood cardioplegia solution (BCP) on cardiac function, metabolism, and infarct size in a rat heart model of myocardial infarction.MethodsFollowing euthanasia, the hearts of 50 rats were quickly excised, cannulated, and inserted into a blood-perfused isolated heart apparatus. A regional myocardial infarction was created in the infarction group (18 hearts) for 120 min; the control group (32 hearts) was not subjected to infarction. In each group, either Buckberg BCP or Bretschneider CCP was administered for an aortic clamping time of 90 min. Functional parameters were recorded during reperfusion: coronary blood flow, left ventricular developed pressure (LVDP) and contractility (dp/dt max). Infarct size was determined by planimetry. The results were compared between the groups using analysis of variance or parametric tests, as appropriate.ResultsCardiac function after acute myocardial infarction, 90 min of cardioplegic arrest, and 90 min of reperfusion was better preserved with Buckberg BCP than with Bretschneider CCP relative to baseline (BL) values (LVDP 54 ± 11% vs. 9 ± 2.9% [p = 0.0062]; dp/dt max. 73 ± 11% vs. 23 ± 2.7% [p = 0.0001]), whereas coronary flow was similarly impaired (BCP 55 ± 15%, CCP 63 ± 17% [p = 0.99]). The infarct in BCP-treated hearts was smaller (25% of myocardium) and limited to the area of coronary artery ligation, whereas in CCP hearts the infarct was larger (48% of myocardium; p = 0.029) and myocardial necrosis was distributed unevenly to the left ventricular wall.ConclusionsIn a rat model of acute myocardial infarction followed by cardioplegic arrest, application of BCP leads to better myocardial recovery than CCP.

Custodiol cardioplegia solution compared to cold blood cardioplegia in pediatric cardiac surgery: a single-institution experience.

Custodiol is an intracellular, crystalloid cardioplegia solution that is a single-dose alternative to multi-dose cold blood cardioplegia; however, there is scarce data regarding its use in infants and children. The objective of this study was to compare its impact on myocardial function in infants. Single-center retrospective review including 132 patients <12 months old undergoing biventricular repair. There were 106 patients who received single-dose Custodiol and 27 patients who received multi-dose blood cardioplegia. Demographic and echocardiographic data were compared between the two groups. Patients receiving Custodiol were slightly younger (100 ± 62 days) and lower weight (4.7 ± 1.3 kg) compared to 152 ± 86 days and 5.2 ± 1.3 kg for blood cardioplegia (p < 0.05). The Society of Thoracic Surgeons/European Association for Cardio-Thoracic Surgery Congenital Heart Surgery score was similar between both groups. Average cardiopulmonary bypass time was similar between both groups (Custodiol 93 ± 54 minutes vs. blood 81 ± 44 minutes, p = 0.46) as was aortic cross-clamp time (Custodiol 58 ± 33 minutes vs. cold blood 53 ± 33 minutes, p = 0.62). Pre-operative left ventricular ejection fraction was similar for blood 73 ± 8% versus Custodiol 70 ± 9%, p = 0.21. There was also no intergroup difference in left ventricular ejection fraction 24 hours post op (blood 64 ± 9% vs. Custodiol 65 ± 12%, p = 0.53) or at discharge (blood 66 ± 10% vs. Custodiol 66 ± 11%, p = 0.95). The pre-operative right ventricle function by fractional area change was also similar in blood cardioplegia (46 ± 13%) versus Custodiol (48 ± 9%, p = 0.38) and showed similar drops in parameters in the two groups 24 hours after surgery and at discharge. Single-dose Custodiol is as safe as blood cardioplegia for myocardial protection in congenital cardiac surgery for the cross-clamp times evaluated in this study. Evaluation at longer cross-clamp times would be helpful to determine if there is a greater benefit to single-dose Custodiol versus more repeated doses of blood cardioplegia for longer cross-clamp times.

The protective effects of L-carnitine on myocardial ischaemia-reperfusion injury in patients with rheumatic valvular heart disease undergoing CPB surgery are associated with the suppression of NF-κB pathway and the activation of Nrf2 pathway.

Myocardial ischaemia-reperfusion injury (MIRI) is a main pathophysiologic change following CPB surgery. L-carnitine, a natural amino acid, is able to transport fatty acids for generating energy and has a protective effect on MIRI. We aim to investigate the protective effect of L-carnitine on MIRI in patients with rheumatic valvular heart disease (RVHD) performed CPB surgical operation and the underlying mechanism. In this study, patients were randomized to three groups. L-carnitine was added to the crystalloid cardioplegic solution for experimental group 1 (6g/L) and experimental group 2 (12g/L), whereas no L-carnitine was used in the control group. Our results showed that L-carnitine significantly attenuated myocardial injury after surgery in these patients. L-carnitine decreased serum markers of myocardial injury including CK-MB, cTnI, hs-cTnT and IMA. L-carnitine increased left ventricular ejection fraction (LVEF) but reduced wall motion score index (WMSI) after operation. L-carnitine also inhibited myeloperoxidase (MPO) activity and inflammatory cytokines in the myocardium of patients after unclamping the aorta. Additionally, L-carnitine increased levels of superoxide dismutase (SOD) and catalase (CAT) while decreased levels of malondialdehyde (MDA) and protein carbonyl content in the myocardium of patients after unclamping the aorta. Moreover, L-carnitine suppressed the activation of nuclear factor kappa B (NF-κB) and activated nuclear factor erythroid 2-related factor 2 (Nrf2). There was also no significant difference in these indices between two experimental groups after unclamping the aorta. Taken together, L-carnitine had a protective effect against CPB-induced MIRI in patients with RVHD, which might be related to its modulation of NF-κB and Nrf2 activities.

The Use of del Nido Cardioplegia for Myocardial Protection in Isolated Coronary Artery Bypass Surgery

The del Nido (DN) cardioplegia solution has been widely used in paediatric open-heart surgery for years; however, its application in adult open-heart surgery has not yet gained sufficient popularity. We investigated the safety and efficiency of the DN cardioplegia solution versus the traditional crystalloid cardioplegia solution [St. Thomas' Hospital (STH) cardioplegia solution] in adult patients undergoing coronary artery bypass grafting (CABG). A retrospective comparative analysis of 200 consecutive patients undergoing isolated on-pump CABG between April 2016 and September 2017 was performed. Patients were divided into two groups: DN group (n = 100) and STH group (n = 100). Groups were compared with regard to perioperative clinical outcomes, and the safety and efficiency of the DN cardioplegia solution in CABG surgery were evaluated. In the DN group, mean aortic cross-clamp, cardiopulmonary bypass, and total operation times were significantly shorter than in the STH group. After the release of the aortic cross-clamp, the requirement for intraoperative defibrillation was significantly less in the DN group. There were no significant differences between the groups in terms of the levels of perioperative cardiac biomarkers (including creatine kinase-myocardial band and troponin I), major postoperative adverse events, and in-hospital mortality. This study revealed that the use of the DN cardioplegia solution in adult patients undergoing isolated CABG provides significantly shorter aortic cross-clamp, cardiopulmonary bypass, and total operation times compared with the traditional cardioplegias solution. The DN solution could be used as a safe and efficient alternative to the traditional cardioplegia solutions in CABG surgery.

Comparative Analysis of Myocardial Protection with HTK Solution and Hypothermic Hyperkalemic Blood Solution in the Correction of Acyanogenic Congenital Cardiopathies - A Randomized Study.

ObjectiveThe goal of the present study was to compare the myocardial protection obtained with histidine-tryptophan-ketoglutarate (HTK) cardioplegic solution (Custodiol®) and with intermittent hypothermic blood solution.MethodsTwo homogenous groups of 25 children with acyanotic congenital heart disease who underwent total correction with mean aortic clamping time of 60 minutes were evaluated in this randomized study. Troponin and creatine kinase-MB curves, vasoactive-inotropic score, and left ventricular function were obtained by echocardiogram in each group. The values were correlated and presented through graphs and tables after adequate statistical treatment.ResultsIt was observed that values of all the studied variables varied over time, but there was no difference between the groups.ConclusionWe conclude that in patients with acyanotic congenital cardiopathies submitted to total surgical correction, mean aortic clamping time around one hour, and cardiopulmonary bypass with moderate hypothermia, the HTK crystalloid cardioplegic solution offers the same myocardial protection as the cold-blood hyperkalemic cardioplegic solution analyzed, according to the variables considered in our study model.

Comment on “Lidocaine and pinacidil added to blood versus crystalloid cardioplegic solutions: study in isolated hearts”

Comment on “Lidocaine and pinacidil added to blood versus crystalloid cardioplegic solutions: study in isolated hearts”

Type of cardioplegic solution as a factor influencing the clinical outcome of open-heart congenital procedures.

IntroductionCardioplegia is one of the most important modalities of myocardial protection during heart surgery.AimTo assess the impact of blood cardioplegia on postoperative variables, in comparison with two types of crystalloid cardioplegic solutions during pediatric heart surgery.Material and methodsOne thousand one hundred and twenty-nine patients underwent surgical correction of congenital heart disease with cardioplegia administration between 2006 and 2012. Nonlinear regression models of postoperative low cardiac output syndrome (LCOS) incidence, catecholamine index and total complication count were developed using a genetic algorithm. The Akaike information criterion was applied for selection of the best model. The following explanatory variables were evaluated: cardioplegia type (ST – Saint Thomas, n = 440; FR – Fresenius, n = 432; BL – Calafiore, n = 257), congenital heart diseases (CHD) type, age, sex, genetic disorder presence, body surface area (BSA), cardiopulmonary bypass (CBP) time, aortic cross-clamp time, operation urgency, redo surgery, surgeon.ResultsLow cardiac output syndrome presence and higher than average catecholamine indexes were negatively influenced by use of crystalloid cardioplegia (ST or FR), presence of specific CHDs, redo surgery and prolonged CBP time. Increased complication count was related to: crystalloid cardioplegia, presence of specific CHDs, redo surgery, urgency of operation, operation time and CBP time. Higher BSA had a protective effect against higher catecholamine index and increased complication count. Older age was protective against LCOS.ConclusionsCardioplegic solutions type influences postoperative variables in children after heart surgery by the negative impact of crystalloid cardioplegia. Blood cardioplegia presents potential advantages for patients – its application may reduce the incidence of low cardiac output syndrome and related complications.

Danshen-Enhanced Cardioprotective Effect of Cardioplegia on Ischemia Reperfusion Injury in a Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Model.

Myocardial ischemia-reperfusion (I/R) injury is unavoidable during cardioplegic arrest and open-heart surgery. Danshen is one of the most popular traditional herbal medicines in China, which has entered the Food and Drug Administration-approved phase III clinical trial. This study was aimed to develop a human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) model to mimic I/R injury and evaluate the cardioprotective effect of regular cardioplegic solution with Danshen. hiPSC-CMs were cultured with the crystalloid cardioplegic solution (Thomas group) and Thomas solution with 2 or 10 µg/mL Danshen (Thomas plus Danshen groups). The cells under normoxic culture condition served as baseline group. Then, the cells were placed in a modular incubator chamber. After 45 min hypoxia and 3 h reoxygenation, hiPSC-CMs subjected to hypoxia/reoxygenation resulted in a sharp increase of reactive oxygen species (ROS) content in Thomas group versus baseline group. Compared with the Thomas group, ROS accumulation was significant suppressed in Thomas plus Danshen groups, which might result from elevating the content of glutathione and enhanced activities of superoxide dismutase and glutathione peroxidase. The enhanced L-type Ca2+ current in hiPSC-CMs after I/R injury was also significantly decreased by Danshen, and meanwhile intracellular Ca2+ level was reduced and calcium overload was suppressed. Thomas plus Danshen groups also presented less irregular transients and lower apoptosis rates. As a result, Danshen could improve antioxidant and calcium handling in cardiomyocytes during I/R and lead to reduced arrhythmia events and apoptosis rates. hiPSC-CMs model offered a platform for the future translational study of the cardioplegia.

Celsior Versus Microplegia: Analysis of Myocardial Protection in Elective Aortic Valve Replacement

Previous studies have analyzed the efficacy of crystalloid cardioplegic solutions, but the use of Celsior (Genzyme Corp, Boston, MA) as a crystalloid cardioplegic solution has not been evaluated. In this observational retrospective study, Celsior crystalloid solution was compared with an all-blood continuous myocardial protection (microplegia). The study included all patients who underwent elective aortic valve replacement operations in whom the myocardial protection was Celsior or microplegia. The primary end points were surrogates of myocardial protection and death at 30 days. The secondary end point was the safety analysis of the use of Celsior. The study included 631 patients, divided in two groups: 219 (34.7%) with microplegia and 412 (65.3%) with Celsior. Troponin T release accurately predicted postoperative death (area under the receiver operating characteristic curve= 0.85). Troponin T increased with the duration of clamp time, and the adjusted time-related increase was lower in the Celsior group. There were no statistically significant differences in the postoperative use of inotropic medication or intraaortic balloon pump. Adjusted postoperative death was lower in Celsior group (odds ratio, 0.33; 95% confidence interval, 0.15 to 0.76). There were no allergic reactions attributed to Celsior and no unexpected toxicity with the use of Celsior (coagulopathy, renal dysfunction, liver dysfunction, or encephalopathy). Isolated crystalloid Celsior may be an optimal and safe myocardial protection strategy in aortic valve replacement operations.

Myocardial Protective Effects of L-Carnitine on Ischemia-Reperfusion Injury in Patients With Rheumatic Valvular Heart Disease Undergoing Cardiac Surgery.

The authors used L-carnitine as an ingredient in cardioplegic solution during valve replacement surgery to investigate the protective effect of L-carnitine on myocardial ischemia-reperfusion injury (MIRI) and its possible mechanism. Prospective, randomized study. A tertiary-care hospital. The study comprised 90 patients undergoing valve replacement under cardiopulmonary bypass. Patients were divided randomly into 3 groups. L-carnitine was added to the crystalloid cardioplegic solution for experimental group 1 (3 g/L) and experimental group 2 (6 g/L), whereas no L-carnitine was used in the control group. The remainder of the treatment was identical for all 3 groups. Serum was collected from each patient 1 hour before the surgery and at 2, 6, 24, and 72 hours after unclamping the aorta, and tissue samples were obtained before cardiac arrest and after unclamping the aorta. The postoperative levels of serum aspartate aminotransferase, creatine kinase, creatine kinase-MB isozyme, and lactic acid dehydrogenase and the apoptotic index were all lower in the 2 experimental groups than those in the control group. In addition, each of the aforementioned serum enzyme levels and the apoptotic index in all 3 groups significantly increased after unclamping the aorta compared with baseline levels taken before surgery. Bcl-2 expression was higher and Bax was lower in the 2 experimental groups compared with those of the control group after unclamping the aorta. However, there was no significant difference in all the postoperative indices between the 2 experimental groups. L-carnitine may reduce cardiopulmonary bypass-induced myocardial apoptosis through modulating the expressions of Bcl-2 and Bax, resulting in a protective effect from MIRI.

Supplemental Cardioplegia Immediately before Graft Implantation may Improve Early Post-Transplantation Outcome.

Background: Preservation of cardiac grafts for transplantation is not standardized and most centers use a single administration of crystalloid solution at the time of harvesting. We investigated possible benefits of an additional dose of cardioplegia dispensed immediately before implantation.Methods: Consecutive adult cardiac transplantations (2005–2012) were reviewed. Hearts were harvested following a standard protocol (Celsior 2L, 4–8°C). In 2008, 100 ml crystalloid cardioplegic solution was added and administered immediately before implantation. Univariate and logistic regression analyses were used to investigate risk factors for post-operative graft failure and mid-term outcome.Results: A total of 81 patients, 44 standard (“Cardio−”) vs. 37 with additional cardioplegia (“Cardio+”) were analyzed. Recipients and donors were comparable in both groups. Cardio+ patients demonstrated a reduced need for defibrillation (24 vs. 48%, p = 0.03), post-operative ratio of CK-MB/CK (10.1 ± 3.9 vs. 13.3 ± 4.2%, p = 0.001), intubation time (2.0 ± 1.6 vs. 7.2 ± 11.5 days, p = 0.05), and ICU stay (3.9 ± 2.1 vs. 8.5 ± 7.8 days, p = 0.001). Actuarial survival was reduced when graft ischemic time was >180 min in Cardio− but not in Cardio+ patients (p = 0.033). Organ ischemic time >180 min (OR: 5.48, CI: 1.08–27.75), donor female gender (OR: 5.84, CI: 1.13–33.01), and recipient/donor age >60 (OR: 6.33, CI: 0.86–46.75), but not the additional cardioplegia or the observation period appeared independent predictors of post-operative acute graft failure.Conclusion: An additional dose of cardioplegia administered immediately before implantation may be a simple way to improve early and late outcome of cardiac transplantation, especially in situations of prolonged graft ischemia. A large, ideally multicentric, randomized study is desirable to verify this preliminary observation.

Myocardial protection against global ischemia with Krebs-Henseleit buffer-based cardioplegic solution

BackgroundThe Krebs-Henseleit buffer is the best perfusion solution for isolated mammalian hearts. We hypothesized that a Krebs-Henseleit buffer-based cardioplegic solution might provide better myocardial protection than well-known crystalloid cardioplegic solutions because of its optimal electrolyte and glucose levels, presence of buffer systems, and mild hyperosmolarity.MethodsIsolated Langendorff-perfused rat hearts were subjected to either global ischemia without cardioplegia (controls) or cardioplegic arrest for either 60 or 180 min, followed by 120 min of reperfusion. The modified Krebs-Henseleit buffer-based cardioplegic solution (mKHB) and St. Thomas’ Hospital solution No. 2 (STH2) were studied. During global ischemia, the temperatures of the heart and the cardioplegic solutions were maintained at either 37°C (60 min of ischemia) or 22°C (moderate hypothermia, 180 min of ischemia). Hemodynamic parameters were registered throughout the experiments. The infarct size was determined through histochemical examination.ResultsCardioplegia with the mKHB solution at moderate hypothermia resulted in a minimal infarct size (5 ± 3%) compared to that in the controls and STH2 solution (35 ± 7% and 19 ± 9%, respectively; P < 0.001, for both groups vs. the mKHB group). In contrast to the control and STH2-treated hearts, no ischemic contracture was registered in the mKHB group during the 180-min global ischemia. At normothermia, the infarct sizes were 4 ± 3%, 72 ± 6%, and 70 ± 12% in the mKHB, controls, and STH2 groups, respectively (P < 0.0001). In addition, cardioplegia with mKHB at normothermia prevented ischemic contracture and improved the postischemic functional recovery of the left ventricle (P < 0.001, vs. STH2).ConclusionsThe data suggest that the Krebs-Henseleit buffer-based cardioplegic might be superior to the standard crystalloid solution (STH2).

MicroRNA-27a Regulates Cardiomyocytic Apoptosis During Cardioplegia-Induced Cardiac Arrest by Targeting Interleukin 10–Related Pathways

In this study, experiments were designed to determine whether microRNAs (miRNAs) play a role in the regulation or modulation of cardiomyocytic reactions under cardioplegia-induced cardiac arrest during cardiopulmonary bypass. MicroRNAs play powerful and unexpected roles in numerous cardiovascular diseases. MicroRNA-based therapeutics may provide a unique opportunity to translate this knowledge into the clinical setting. Sprague-Dawley rats (10 per group) were randomly divided into three groups: control, perfusion, and arrest groups. In the perfusion group, isolated hearts were perfused with oxygenated physiologic buffered solution for 3 h using a Langendorff apparatus. In the arrest group, cold crystalloid cardioplegia solution was used to induce and maintain cardiac arrest for 1 h; hearts were reperfused for 2 h with warm oxygenated phosphate-buffered saline solution. Cardiac miRNAs and protein expression patterns were detected using miRNA arrays and two-dimensional fluorescence difference gel electrophoresis followed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Of 103 different miRNAs and 222 different proteins expressed in the three groups, miRNA-27a was the one considered to be related to the regulation of cardiomyocyte apoptosis by targeting the interleukin 10 pathway. Transfection of H9c2 cardiomyocytes with pre-miRNA-27a, which significantly decreased the mRNA and protein levels of interleukin 10 and increased expression of nuclear factor κB and its downstream cytokines during hypoxia/reperfusion injury, could activate caspase 3 and apoptosis. Our study demonstrated the altered expression of miRNAs in cardiomyocytes during cardioplegia-induced cardiac arrest. The involvement of miRNAs in cardiomyocytic apoptosis adds another level of complexity to gene regulation, which could open up novel avenues for cardiac protection strategies during cardiac surgery.