Cardioplegic Solution Research Articles

Safety and Efficacy of Single Dose Del Nido Cardioplegia Solution in Left Ventricular Assist Device Implantation- A Propensity Matched Study

Del Nido cardioplegia (DN) has recently become more in common use as a "single" dose cardioplegia in adult cardiac surgery. However, it is not well described in left ventricular assist device (LVAD) surgery. The purpose of this study was to summarize our clinical experience with single dose DN solution in LVAD implantation and to assess the safety and efficacy of our DN protocol by comparing with conventional cold whole blood cardioplegia (CWB). A total of 524 consecutive patients underwent LVAD implantation between July 2008 and August 2019. Among them, 137 patients who required aortic cross-clamp for concomitant cardiac procedures were included in this study. The DN protocol was to administer the initial dose as a single dose. CWB was given every 20 minutes. Propensity matching identified 40 matched pairs for analysis. Cross-clamp time was significantly shorter in the DN group compared with the CWB group (58± 20 min vs. 70± 33 min, p=0.0497). The retrograde cardioplegia technique was used in 6 (15.0%) patients in the DN group and 36 (90.0%) patients in the CWB group (p<0.0001). There were no significant differences in the rates of postoperative prolonged use of inotropes (>14 days) (DN: 3/40, 7.5% vs. CWB: 3/40, 7.5%, p=1), requiring postoperative right VAD (DN: 2/40, 5.0% vs. CWB: 2/40, 5.0%, p=1), and requiring blood transfusion (Table). Freedom from re-admission at 1 year was similar between two groups (DN: 69.6±7.7% vs. CWB: 74.3±7.5%, Log-Rank p=0.5522). Mid-term clinical outcomes in the patients undergoing LVAD implantation with the DN protocol was acceptable. This study showed the DN protocol was associated with shortened cross-clamp time and less frequent usage of the retrograde cannula technique.

Hypophosphataemia after cardiopulmonary bypass – incidence and clinical significance, a South African perspective

Background: Hypophosphataemia is well-known in the intensive care units (ICU), for example, in refeeding syndrome. There is limited research available for hypophosphataemia in the ‘post-cardiac surgery’ population. Objectives: Defining the incidence of hypophosphataemia after cardiopulmonary bypass, in a South African population. Secondary objectives include the clinical implication of hypophosphataemia on duration of mechanical ventilation, ICU stay, and cardioactive drug support; and possible associations between demographic variables, intraoperative variables (including cardioplegic solution), and the postoperative phosphate levels. Methods: This was a single-centre, non-blinded, prospective cohort analytical study at an academic hospital, in patients presenting for open cardiac surgery. Over a one-year period, 101 patients were included. Preoperative variables included all the factors of the EuroSCORE II risk evaluation score. Intraoperative variables recorded were drug and blood product administration, cardioplegic solution and cardiopulmonary bypass-related variables. Postoperatively, serum phosphate levels were taken daily and postoperative care measures, such as duration of cardioactive drug support, mechanical ventilation, and ICU stay, were recorded. Results: The incidence of hypophosphataemia, immediately postoperative, was 12.6% (95% confidence interval [CI] 6.7–21.0%) and peaked on Day 3 at 29.0% (95% CI 20.1–39.4%). New onset hypophosphataemia at any stage during the ICU stay was 52.6% (95% CI 42.1–63.0%). No significant associations between hypophosphataemia and secondary objectives were found. Conclusion: Hypophosphataemia was common with an incidence higher than expected. This did not translate into a clinical effect, as the degree was usually mild (0.66–0.79 mmol/L).G

Early Outcomes of Custodiol versus Blood Cardioplegia in Coronary Artery Bypass Graft Surgery at Ain Shams University Hospitals

Abstract Background Inadequate myocardial protection in long ischemic periods followed by reperfusion is an issue of concern in cardiac surgery. Cardioplegic solutions improve the tolerance to ischemia and reperfusion by preserving myocardial energy reserves, preventing osmotic and electrolyte imbalances and buffering acidosis. The aim of the study was to compare early outcomes of Histidine–tryptophan–ketoglutarate (HTK) solution versus blood cardioplegia in coronary artery bypass graft surgery at Ain Shams University Hospitals. Methodology This was a retrospective study conducted on patients who underwent isolated elective CABG at the department of cardiothoracic surgery at Ain Shams University Hospitals from the 1stof January, 2017 to the 1st of August, 2018. Results the analysis between these two groups divided as the following: first group who received Histidine–tryptophan–ketoglutarate (HTK) and the second who received conventional blood cardioplegia , There was no statistically significant difference between the two groups of myocardial protection in terms of morbidity and mortality with a p-value &amp;gt;0.05. With a stastically significant increase in Total bypass time with a p value &amp;lt;0.05 and a highly significant difference in terms of post operative Ventilation time and ICU stay which was higher in HTK group with a p-value of &amp;lt; 0.01 between the two groups. Conclusion Conventional blood cardioplegia showed superiority in terms of metabolic recovery based on the incidence of spontaneous defibrillation, ventilation time and ICU stay on the other hand Histidine–tryptophan–ketoglutarate (HTK) cardioplegia is a much more easily administered cardiolplegia technique without the need of preparation or repeated administration. Both Solutions showed efficacy in different areas that could be owed to the small sample size we used which cannot asses the ultimum superiority of one solution over the other .

Del Nido cardioplegia versus blood cardioplegia in adult aortic root surgery

ObjectiveDel Nido cardioplegia solution offers prolonged cardiac protection with single-dose administration; this is particularly interesting for aortic root surgery. However, there is a scarcity of data supporting its safety in adults undergoing complex cardiac surgery, such as aortic root repair. We hypothesized that del Nido cardioplegia solution and blood cardioplegia solution provide equivalent safety during aortic root surgery. MethodsBetween January 2015 and June 2018, 283 consecutive patients undergoing the Ross procedure (204) and valve-sparing operation (79) with del Nido cardioplegia solution or blood cardioplegia solution were 1:1 propensity matched (110 aortic root surgery), and outcomes were compared. Clinical patient characteristics and data were extracted from our local database for valve-sparing operations and for Ross procedures. ResultsPreoperative characteristics were similar between del Nido cardioplegia solution and blood cardioplegia solution after propensity matching (mean age, 48.6 ± 1.5 years). Median postoperative creatine kinase MB isotype did not differ between del Nido cardioplegia solution and blood cardioplegia solution (48.9 [14.9-300] μg/L vs 51.2 [12.4-116] μg/L for blood cardioplegia solution [P = .1]), but there was a trend toward higher troponin T levels with del Nido cardioplegia solution (748 [221-5834] ng/L vs 710 [212-3332] ng/L for blood cardioplegia solution [P = .07]). In patients with myocardial ischemia longer than 180 minutes, median creatine kinase MB isotype was higher in del Nido cardioplegia solution (75.1 [59.3-300] μg/L than in blood cardioplegia solution 60.5 [16.5-116] μg/L [P = .01]). Aortic crossclamp and cardiopulmonary bypass times were shorter with del Nido cardioplegia solution (163 ± 5 vs 181 ± 5 minutes, P = .01 and 145 ± 4 vs 161 ± 4 minutes, respectively, P = .006). Return to spontaneous rhythm was more frequent in the del Nido cardioplegia solution group (52% [29/55] vs 27% [15/55], P = .006). There was no difference in inotropic or vasoactive agent use (P = .8). Postoperative left ventricle ejection fraction was similar (0.54 ± 0.09 vs 0.55 ± 0.08 for del Nido cardioplegia solution and blood cardioplegia solution, respectively; P = .4). There was no difference between groups for perioperative mortality and postoperative complications. ConclusionsDel Nido cardioplegia solution can be used as an alternative to blood cardioplegia solution in adults undergoing complex aortic root surgery, providing comparable clinical outcomes and improved surgical workflow. However, del Nido cardioplegia solution seems to be associated with increased myocardial injury, especially with extended myocardial ischemic times, but this finding did not translate into adverse clinical events. Caution is warranted in adopting this cardioplegic solution in aortic interventions requiring long ischemic times, and further study is required to establish its exact role in complex cardiac surgery.

Impact of Custodiol-N cardioplegia on acute kidney injury after cardiopulmonary bypass.

Myocardial protection during cardiopulmonary bypass (CPB) can be achieved using cardioplegic solutions. Although, acute kidney injury (AKI) is a common complication following CPB, the effects of cardioplegic solutions on AKI have rarely been investigated. Within this study, the effects of the cardioplegic solutions histidine-tryptophan-ketoglutarate (HTK; Custodiol) and HTK-N (Custodiol-N) on AKI in a large animal model were compared. Therefore, Landrace pigs underwent median sternotomy, CPB at 34°C, 90minutes of cardiac arrest and 120minutes of reperfusion. Animals were randomized for single-shot cardioplegia with either HTK (n=10) or HTK-N (n=10). Renal biopsies and sera were analyzed to determine AKI biomarkers and apoptosis. Compared to HTK, HTK-N induced a decreased extent of proximal tubule swelling (48.3±1.6µm vs 52.3±1.1µm, P=.05) and decreased cytochrome c release (0.26±0.04 vs 0.46±0.08, P=.04) without reaching statistical significance due to Bonferroni correction. Comparing baseline and postreperfusion levels, the hemoglobin (Hb) and blood calcium levels were lower in HTK-N (Hbbaseline : 6.0±0.6mmol/L, Hbreperfusion : 6.2±0.7mmol/L, P=.12; Ca2+baseline : 1.36±0.05mmol/L, Ca2+reperfusion : 1.28±0.05mmol/L, P=.16) compared to the HTK group (Hbbaseline : 5.9±0.4mmol/L, Hbreperfusion : 4.7±0.8mmol/L, P<.01; Ca2+baseline : 1.34±0.07mmol/L, Ca2+reperfusion : 1.24±0.06mmol/L, P<.01). The present study showed that HTK-N could positively affect the kidney during CPB. Hb and calcium levels were stabilized. A statistical trend was found showing that AKI-related proximal tubule swelling and cytochrome c release were diminished.

Safety of Custodiol cardioplegia: a cohort study in patients undergoing cardiac surgery with elongated aortic cross-clamp time.

The increasing complexity of patients undergoing cardiac surgery requires extended myocardial ischaemic periods. Cardiac surgeons demand a cardioplegic solution with prolonged myocardial protection. Therefore, we introduced Custodiol in our centre in 2011. The aim of this study was to investigate the safety and efficacy of Custodiol compared with the standard method of cardioplegia. Between 2011 and 2016, 188 adult patients who underwent mitral valve surgery combined with coronary artery bypass grafting were included in this retrospective study. In 113 patients, Custodiol cardioplegia was used to achieve cardiac arrest, while St. Thomas Hospital solution was used in 75 patients. The primary endpoint of the study was the degree myocardial damage which was estimated by the measurement of creatine kinase-myocardial band on the first postoperative day. A linear regression analysis was performed to compare the aortic cross-clamp time with the postoperative myocardial damage in both groups. The extracorporeal circulation time and aortic cross-clamp were significantly longer in the Custodiol group than in the St. Thomas group: 125.6 ± 32.5 minutes versus 93.1 ± 27.7 minutes (p < 0.001), respectively. However, there was no significant difference between the two groups regarding the postoperative levels of creatine kinase-myocardial band (96 (70-140) U/L vs. 86 (69-120) U/L, respectively; p = 0.321). There was no significant differences between the two groups regarding the 30-day mortality (6.1% vs. 5.5%, respectively; p = 1.000) or 120-day mortality (9.6% vs. 11.0%, respectively; p = 0.806). Our findings demonstrate that Custodiol is a safe method of myocardial protection for patients who underwent mitral valve surgery with coronary artery bypass grafting in our hospital. Further investigations extended to more cardiac surgery populations are needed to confirm clinical benefits of Custodiol cardioplegia.

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.

Comparison of Custodiol® and modified St. Thomas cardioplegia for myocardial protection in coronary artery bypass grafting

Background/Aim. Custodiol? is a hyperpolarizing cardioplegic solution which has been used in our national cardiac surgical practice exclusively for the heart transplant surgery. Owing to its numerous advantages over the standard depolarizing solutions, Custodiol? became cardioplegic solution of choice for all other cardiac surgical procedures in many cardio-surgical centers. This study evaluated myocardial protection by Custodiol? compared to modified St. Thomas cardioplegic solution in coronary artery bypass surgery. Methods. In a prospective four-month study, 110 consecutive adult patients who underwent primary isolated elective on-pump coronary artery bypass grafting (CABG) were randomized into the Custodiol? group (n = 54) and the St. Thomas groupa (n = 50), based on the type of administered cardioplegia; six patients were excluded. Cardiac protection was achieved as antegrade cold crystalloid cardioplegia by one of the solutions. Myocardial preservation was assessed through following outcomes: spontaneous rhythm restoration post cross-clamp, and postpoperative cardiac specific enzymes level, ejection fraction (EF) change, inotropic support, myocardial infarction (MI), atrial fibrillation (AF), and death. Results. Preoperative and intraoperative characteristics of patients in both groups were similar except for a considerably longer cross-clamp time in the Custodiol? group (49.1 ? 19.0 vs. 41.0 ? 12.9 minutes; p = 0.022). The Custodiol? group exhibited a higher rate of return to spontaneous rhythm compared to the St. Thomas group (31.5% vs. 20.0%, respectively; p = 0.267), lower rates of AF (20.4% vs. 28%, respectively; p = 0.496), MI (1.8% vs. 10.0%, respectively; p = 0.075) and inotropic support (9.0% vs. 12.0%, respectively; p = 0.651), albeit not statistically significant. There was an insignificant difference in peak value of troponin I between the Custodiol? and Thee St. Thomas group (5.0 ? 3.92 ?g/L vs. 4.5 ? 3.39 ?g/L, respectively; p = 0.755) and creatine kinase-MB (26.9 ? 15.4 ?g/L vs. 28.5 ? 24.2 ?g/L, respectively; p = 0.646) 6 hours post-surgery. EF reduction was comparable (0.81% vs. 1.26%; p = 0.891). There were no deaths in both groups. Conclusions. Custodiol? and modified St.Thomas cardioplegic solution have comparable cardioprotective effects in CABG surgery. The trends of less frequent MI, AF and ino-tropic support, despite the longer cross-clamp time in the Custodiol? group may suggest that its benefits could be ascertained in a larger study.

Comparison of Post Operative Outcomes Following Del Nido Cardioplegia Versus Howards Cardioplegia in Adult Cardiac Surgery at Pakistan Institute of Medical Sciences

This study compares post-operative outcomes for ionotropic support, defibrillator need and duration of hospital stay in adult patients of cardiac surgery following Del Nido cardioplegia versus Howard’s cardioplegia and also compare pre and post operative Cardiac enzymes and serum potassium levels, assessment of pre and post operative Arrthymias. It was an Observational study conducted at Pakistan Institute of Medical Sciences Islamabad Pakistan. Patients were divided into 2 groups. Group (A) patients were Del Nido cardioplegia and Group (B) patients were Howard’s cardioplegia. Data was collected by using non-probability Consecutive Sampling technique. 100 patients were enrolled in this study randomly allocating 50 to each study group. Results of the study show that Post-op CKMB level after 24 hours for Howard group was (127.5200±103.59069) and for DN group (67.3540±23.21292). Similarly post op Potassium level for Howard group was (4.9742±.77010) and for DN group was (4.5590±.65033), Duration of hospital stay for Howard’s group was (9.60±.857) and for DN group was (8.58±1.486). High ionotropic support was required in Howard’s group as compared to DN where it was mild to moderate. 40% patients required defibrillation in Howards as compared to DN with only 20%. It is concluded that Cardioplegia is intended for brief cardiac arrest, which is an important function during cardiopulmonary Bypass surgery. After comparing two cardioplegic solutions namely Del Nido and Howard’s cardioplegia. Our study concludes that Del-Nido cardioplegia provide better myocardial protection and less cross clamp and bypass time. Cardiac enzymes, serum potassium level and post-op arrthymias show better profile in Del-Nido as compared to Howard’s cardiolpegia. Our data clearly advocate the efficacy and safety of Del-Nido over Howard’s cardioplegia. It is very safe and effective as compared to Howards.

Effect of single-dose crystalloid cardioplegic agent compared to bloody cardioplegic agent in cardiac surgery in children with Tetralogy of Fallot.

BACKGROUNDCardioplegia is one of the main post-operative cardiac protective factors widely used in recent decades in the form of crystalloid (St. Thomas) and bloody solutions [del Nido (DN)]. The purpose of this study was to compare the effect of a crystalloid cardioplegic agent (St. Thomas) with that of a bloody cardioplegic agent (DN) in pediatric cardiac surgery among children with Tetralogy of Fallot (TOF).METHODSThis study was performed on 60 children with TOF, who were candidates for heart repair surgery. The participants were randomly divided into two groups of crystalloid cardioplegic agent and bloody cardioplegic agent. Operative outcomes such as required time for onset of heart arrest, duration of returning to normal heart rhythm, and cardiopulmonary bypass (CPB) time, and operative complications were compared between the two groups.RESULTSThe duration of returning to normal heart rhythm (50.43 ± 10.93 seconds vs. 43.03 ± 16.35 seconds; P = 0.044) and duration of inotropy (80.40 ± 27.14 hours vs. 63.20 ± 26.91 hours; P = 0.017) were significantly higher in the DN group compared to the St. Thomas group. However, there were no significant differences between the two groups in terms of heart arrest time, cross-clamp time, CPB time, supplementary lasix time, duration of intubation, and intensive care unit (ICU) and hospital length of stay (LOS) (P > 0.050).CONCLUSIONThe use of St. Thomas cardioplegic solution was more effective in reducing the duration of returning to normal heart rhythm and inotropy compared with DN cardioplegic agent, and a single dose of these two cardioplegic agents can keep the mean cardiac arrest duration within the range of 50-70 minutes. It seems that the use of St. Thomas cardioplegic solution can be suggested in pediatric heart surgery.

Comparison of the operative and postoperative effects of del Nido and blood cardioplegia solutions in cardiopulmonary bypass surgery.

ObjectiveOur goal was to compare the operative and postoperative effects of del Nido cardioplegia (DN group) and blood cardioplegia (BC group) performed in cardiac surgery.MethodsA total of 83 patients were included, separated into DN group and BC group. The operative and postoperative effects of the two groups were compared for the first 24 hours until extubation. The operative and postoperative complete blood count (CBC), biochemical values and clinical parameters were compared.ResultsThe first control activated clotting time (ACT) levels in DN group patients were lower (P=0.003) during the operation. The amount of cardioplegia in DN group were lower than that in BC group (P=0.001). The pump outflow and postoperative lactate level of DN group were lower than those of BC group (P=0.005, P=0.018, respectively), as well as the amounts of NaHCO3 (P=0.006) and KCl (P=0.001) used during the operation. The same occurred with the first monocytes (Mo) and mean corpuscular volume (MCV) levels in the postoperative intensive care unit (P=0.006, P=0.002). However, the first glucose level and the eosinophil (Eo) level were higher in DN group (P=0.011, P=0.047, respectively).ConclusionIn the operative evaluation, the amount of cardioplegia, the first ACT levels, the pump outflow lactate level and the amounts of NaHCO3 and KCl in DN group were lower. In postoperative evaluation, measured level of lactate, Mo and MCV in DN group were all lower; their glucose and Eo levels were higher.

The Effects of Cold Blood Cardioplegia with and without Adenosine on Hemodynamic Status of Patients Undergoing Mitral Valve Surgery

Background: Minimizing ischemic-reperfusion injury following valvular heart surgeries is very important with the goal of providing appropriate cardiac systolic function, preventing arrhythmic events as well as inhibiting ischemic related processes. Due to the protective effects of adenosine, this chemical has been used as an additive to a cardioplegic solution for achieving this purpose. Objectives: The present study aimed to assess the effects of cold blood cardioplegia with adenosine on hemodynamic status of patients undergoing mitral valve surgery. Methods: This randomized single-blinded clinical trial was performed on 40 consecutive patients who were candidates for mitral valve surgery. The patients were randomly assigned to receive cold blood cardioplegia in combination with or without adenosine or hyperkalemic cardioplegia as the control. Primary endpoints were returning sinus rhythm, requiring inotropes after cardiopulmonary bypass and secondary endpoints were the change in hemodynamic parameters and postoperative complications. Results: Except for mean time required for induction of cardiac arrest that was significantly shorter in intervention group, no differences were found between the two groups regarding cardiopulmonary bypass time, cross clamp duration, and rhythm return time. In assessment of postoperative consequences, there were no differences in post-procedural events with respect to returning sinus rhythm, requiring inotropes, requiring DC shock, mean intubation time, length of ICU stay and also left ventricular systolic function. Conclusions: Except for reducing the time for inducing cardiac arrest within mitral valve surgery, adding adenosine to cold blood cardioplegia may not be beneficial regarding the improvement of postoperative outcome.

Myocardial protection technique structured on cardiac mass.

Myocardial protection is crucial in cardiac surgery: quantification is often difficult as there is a significant mismatch between body weight and heart weight as per geometric remodeling. This study has the objective to compare two groups of patients on the administration of myocardial protection in valvular pathologies: the first group has indexed the administration with left ventricular mass index; the second has indexed it on the body weight or on the body surface area. The primary endpoint of double-blind case-control study is to detect the difference in incidence in terms of post-operative low cardiac output syndrome. A single-center double-blind case-control study in a specialized regional tertiary cardiac surgery center in Italy. Between March 2017 and September 2018, 200 adults (100 per Group A vs. Group B) were scheduled for elective procedures: Group A (50 aortic valve replacement-50 mitral valve repair in minimally invasive cardiac surgery) used blood cardioplegic solution with Saint Thomas I solution, with calculation of left ventricular mass index with echocardiographic measures (Formula Group A); Group B (50 aortic valve replacement-50 mitral valve repair in minimally invasive cardiac surgery) used blood cardioplegic solution with Saint Thomas I solution, with calculation indexed on the body surface area, Du Bois Method (Formula Group B). A statistically significant difference was found for Student's t-test in patients who used myocardial indexed protection on left ventricular mass index versus control: aortic valve replacement procedures in aortic valve stenosis-ejection fraction (24 hours, p-value = 0.046), TnT (24 hours, p-value = 0.047), stroke volume shift (24 hours, p-value = 0.043), and infusion of epinephrine after cardiopulmonary bypass (p-value = 0.033); aortic valve replacement procedures in aortic valve insufficiency-ejection fraction (24 hours, p-value = 0.044), TnT (24 hours, p-value = 0.047), stroke volume shift (24 hours, p-value = 0.046), and infusion of Epinephrine after cardiopulmonary bypass (p-value = 0.029). No statistically significant differences in patients undergoing mitral valve repair surgery. The study group in the aortic valve surgery that administered myocardial protection indexed for the left ventricular mass index and showed a statistically significant lower incidence for post-operative low cardiac output syndrome compared to the control group.

Intact coronary and myocardial functions after 24 hours of non-ischemic heart preservation

Objectives. The aim of this study was to investigate endothelium dependent relaxation (EDR) in coronary artery and the myocardial contractility after 24 h of non-ischemic heart preservation (NIHP). Design. Explanted cardioplegic hearts from six pigs were preserved by NIHP for 24 h. The perfusion medium consisted of an albumin containing hyperoncotic cardioplegic nutrition-hormone solution with erythrocytes to a hematocrit of 10%. Coronary artery ring segments were then studied in organ baths. Thromboxane A2 was used for vasocontraction and Substance P to elicit endothelium dependent relaxation. A heart trabecula from the right ventricle was mounted in an organ bath and a special stimulation protocol was used to characterize myocardial contractility. Fresh cardioplegic hearts from 11 pigs were used as controls. The water content of the hearts was calculated. Results. There was no significant difference between NIHP and fresh controls regarding EDR (91.2 ± 1.2% vs 93.1 ± 1.8%). The contraction force, potentiation and calcium recirculation fraction did not differ between the groups. The water content of the myocardium was 79.3 ± 0.2% for NIHP and 79.5 ± 0.2% for controls. Conclusions. NIHP for 24 h keeps coronary artery EDR and myocardial contractility intact and causes no edema.

Effects of histidine load on ammonia, amino acid, and adenine nucleotide concentrations in rats.

The unique capability of proton buffering is the rationale for using histidine (HIS) as a component of solutions for induction of cardiac arrest and myocardial protection in cardiac surgery. In humans, infusion of cardioplegic solution may increase blood plasma HIS from ~ 70 to ~ 21,000µM. We examined the effects of a large intravenous dose of HIS on ammonia and amino acid concentrations and energy status of the body. Rats received 198mM HIS intravenously (20ml/kg) or vehicle. Samples of blood plasma, urine, liver, and soleus (SOL) and extensor digitorum longus (EDL) muscles were analysed at 2 or 24h after treatment. At 2h after HIS load, we found higher HIS concentration in all examined tissues, higher urea and ammonia concentrations in blood and urine, lower ATP content and higher AMP/ATP ratio in the liver and muscles, higher concentrations of almost all examined amino acids in urine, and lower glycine concentration in blood plasma, liver, and muscles when compared with controls. Changes in other amino acids were tissue dependent, markedly increased alanine and glutamate in the blood and the liver. At 24h, the main findings were lower ATP concentrations in muscles, lower concentrations of branched-chain amino acids (BCAA; valine, leucine, and isoleucine) in blood plasma and muscles, and higher carnosine content in SOL when compared with controls. It is concluded that a load of large HIS dose results in increased ammonia levels and marked alterations in amino acid and energy metabolism. Pathogenesis is discussed in the article.

Effect of Selenium Added to the Cardioplegic Solution on Cardiac Protection in Coronary Artery Bypass Grafting Surgeries: A Randomized, Double-Blinded, Clinical Trial Study

Background: Coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass (CPB) triggers an inflammatory reaction, leading to the development of myocardial damage and dysfunction. Selenium is the main cofactor for many antioxidant enzymes. Selenium level is decreased during heart surgeries affecting the cardiopulmonary pump, which in turn can aggravate the organ and heart dysfunction and mortality. Objectives: The aim of this study was to evaluate the cardiac protective effects of adding selenium to cardioplegia solution in these surgeries. Methods: In this randomized, double-blind, clinical trial study that was conducted in the department of cardiac surgery of Shiraz University of Medical Sciences (SUMS) in Shiraz, Iran, 67 elected CABG patients were allocated to the two control or selenium groups. In the intervention group, 1000 μg sodium selenite was added to cardioplegia solution. The same amount of normal saline was added to the cardioplegia solution in the control group. Arterial blood samples were withdrawn before anesthesia induction (T1), immediately after the surgery (T2), as well as, 6 and 24 hours after the surgery (T3 and T4 respectively), to determine the CK-MB and Troponin I levels. Results: According to our findings, the CK-MB and Troponin I cardiac enzyme levels were significantly different, considering different time points (P 0.05). There were also no significant differences between the two groups regarding systolic and diastolic blood pressures. Conclusions: The administration of 1000 µg sodium selenite via cardioplegia solution had no significant cardioprotective effect during coronary bypass surgery in CABG patients.

The method of heterotopic rat heart transplantation for investigation the cardioprotective efficacy of cardioplegic solutions

This article describes in detail the modified method of heterotopic heart transplantation in rats. The methods of animal anesthesia, surgical features of the removal of a donor heart and its implantation to a recipient rat are described in detail. The advantages and disadvantages of donor heart preservation methods are described, as well as methods for evaluating a donor heart preparation, the quality of preservation and the effectiveness of cardioprotection. Experimental approaches to the study of the effectiveness of cardioplegic and preservative solutions using this technique are proposed. The data of our own pilot study on a comparative analysis of the effectiveness of cardioprotection using preservative solutions using this experimental model are presented.

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.

Enhanced Activity by NKCC1 and Slc26a6 Mediates Acidic pH and Cl- Movement after Cardioplegia-Induced Arrest of db/db Diabetic Heart.

Diabetic heart dysfunctions during cardiac surgeries have revealed several clinical problems associated with ion imbalance. However, the mechanism of ion imbalance mediated by cardioplegia and a diabetic heart is largely unclear. We hypothesized that ion transporters might be regulated differently in the diabetic heart and that the differentially regulated ion transporters may involve in ion imbalance of the diabetic heart after cardioplegic arrest. In this study, we modified the Langendorff-free cardioplegia method and identified the involved ion transporters after cardioplegia-induced arrest between wild type and db/db heart. Enhanced expression of Na+-K+-2Cl− cotransporter 1 (NKCC1) was observed in the db/db heart compared to the wild type heart. Enhanced NKCC1 activity was observed in the left ventricle of db/db mice compared to that of wild type after cardioplegia-induced arrest. The expression and activity of Slc26a6, a dominant Cl−/HCO3− exchanger in cardiac tissues, were enhanced in left ventricle strips of db/db mice compared to that of wild type. The Cl− transporting activity in left ventricle strips of db/db mice was dramatically increased as compared to that of wild type. Interestingly, expression of Slc26a6, as well as carbonic anhydrase IV as a supportive enzyme of Slc26a6, was increased in db/db cardiac strips compared to wild type cardiac strips. Thus, the enhanced Cl− transporting activity and expression by NKCC1 and Slc26a6 in db/db cardiac tissues after cardioplegia-induced arrest provide greater insight into enhanced acidosis and Cl− movement-mediated db/db heart dysfunction. Thus, we suggested that enhanced Cl− influx and HCO3− efflux through NKCC1 and Slc26a6 offer more acidic circumstances in the diabetic heart after cardioplegic arrest. These transporters should be considered as potential therapeutic targets to develop the next generation of cardioplegia solution for protection against ischemia-reperfusion injury in diabetic hearts.

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.