Intermittent Cold Blood Cardioplegia Research Articles

Efficacy and Safety of Multidose del Nido Cardioplegia for Optimal Myocardial Protection in Isolated Coronary Artery Bypass Grafting Surgery: A Comparative Retrospective Cohort Study

Background: The perioperative outcomes of del Nido cardioplegia (DNC) as a single-dose solution have been investigated in cardiac surgical procedures. However, the optimal redosing interval for multiple doses of DNC remains an area of ongoing debate. The purpose of this study is to evaluate the safety and efficacy of multidose DNC administered according to our protocol in comparison to intermittent cold blood cardioplegia (BC) in isolated coronary artery bypass grafting (CABG) patients. Methods: A retrospective analysis was conducted on 79 consecutive isolated CABG patients between January 2022 and March 2023. The Patients were divided into two groups: the DNC group (n = 35), and the BC group (n = 44). Perioperative clinical characteristics, cardiac enzyme levels, and postoperative complications were compared between the groups. DNC was applied in a 1:4 (crystalloid:blood) ratio, with an initial dose of 20 mL/kg. Maintenance doses of 10 mL/kg were given every 45 to 50 minutes. A half dose was given if the aortic cross-clamp was expected to last less than 60 minutes. Warm blood was applied before releasing the aortic cross-clamp. Results: Both groups demonstrated comparable mean aortic cross-clamp and cardiopulmonary bypass times. At 24 hours postoperatively, troponin T levels were significantly lower in the DNC group (p ˂ 0.001), while creatine kinase-myocardial band (CK-MB) levels were higher (p ˂ 0.001). The DNC group required lower defibrillation rates than the BC group (p = 0.008). Multivariate logistic regression analysis revealed that the requirement for defibrillation (odds ratio (OR) = 10.9, 95% confidence interval (CI): 2.9–41.8, p < 0.001), cross-clamp time (OR = 1.04, 95% CI: 1.02–1.1, p = 0.002) and body mass index (BMI) (OR = 0.8, 95% CI: 0.7–0.9, p = 0.030) were independent risk factors for low cardiac output syndrome. DNC and left ventricle ejection fraction >40% were associated with a return to sinus rhythm (OR = 3.6, 95% CI: 1.3–10.1, p = 0.013 and OR = 3.1, 95% CI: 1.1–8.7, p = 0.035, respectively). No significant differences were found in terms of postoperative adverse events, and in-hospital mortality. Conclusion: Multidose DNC in CABG patients provides equivalent clinical outcomes and myocardial protection compared to BC. In addition, the findings suggest that the redosing interval strategy employed in the DNC protocol is acceptable.

Warm versus cold-blood cardioplegia in paediatric congenital heart surgery: a randomized trial.

Intermittent cold blood cardioplegia is commonly used in children whereas intermittent warm blood cardioplegia is widely used in adults. We aimed to compare clinical and biochemical outcomes with these two methods. A single centre, randomized controlled trial was conducted to compare the effectiveness of warm (≥34°C) versus cold (4-6°C) antegrade cardioplegia in children. The primary outcome was cardiac troponin T over the first 48 postoperative hours. Intensive care teams were blinded to group allocation. Outcomes were compared by intention-to-treat using linear mixed-effects, logistic, or Cox regression. 97 participants with median age of 1.2 years were randomized (49 to warm, 48 to cold cardioplegia); 59 participants (61%) had a risk-adjusted congenital heart surgery score of 3 or above. There were no deaths and 92 participants were followed to 3-months. Troponin release was similar in both groups (geometric mean ratio 1.07; 95% confidence interval [CI], 0.79-1.44; P = 0.66), as were other cardiac function measures (echocardiography, arterial and venous blood gases, vasoactive-inotrope score, arrhythmias). Intensive care stay was on average 14.6 hours longer in the warm group (hazard ratio 0.52; 95% CI, 0.34-0.79; P = 0.003), with a trend towards longer overall hospital stays (hazard ratio 0.66; 95% CI, 0.43-1.02; P = 0.060) compared with the cold group. This could be related to more unplanned reoperations on bypass in the warm group compared to cold group (3 vs 1). Warm blood cardioplegia is a safe and reproducible technique but does not provide superior myocardial protection in paediatric heart surgery. ISRCTN13467772.

COMPARISON STUDY: INTERMITTENT ANTIGRADE WARM CARDIOPLEGIA VERSUS ANTIGRADE COLD INTERMITTENT BLOOD CARDIOPLEGIA FOR MYOCARDIAL PROTECTION DURING ELECTIVE ON PUMP CORONARY ARTERY BYPASS GRAFTING IN EARLY POST-OPERATIVE PERIOD

Background: Defending the heart against potential damage during cross-clamping is the most important and vital step to ensuring a successful surgical outcome(1). The creation of cardioplegia solutions was one of the major advances in cardiac surgery that allowed surgeons to conduct complicated surgical procedures to avoid myocardial injury (14). Treating cardioplegia at a cool temperature would be a significant factor in lowering myocardial metabolism. However, the reduction in myocardial metabolism due to hypothermia, compared with that achieved by diastolic arrest, is usually very negligible. Since Normothermias enzymatic and cellular processes work better (7). Owing to the propensity of the heart to resume electrical operation during normothermia, however, this must be administered consistently or only with short interruptions (4). Terminal warm blood cardioplegia (hot shot) is normally done just before the elimination of the aortic cross-clamp since it has been demonstrated that myocardial metabolism is increasing (23). Methods: A prospective controlled randomised study (200 hundred patients aged 40 to 65 years of both sexes underwent elective CABG pump surgery) will be included. They will be divided into three groups of patients: Group I:includes 100 Patients who received intermittent cold blood cardioplegia. Group II:includes 100 Patients who received intermittent warm blood cardioplegia with controlled reperfusion for 3 minutes before aortic unclamping. Study made from January, 2019 to August, 2020, at National Heart Institute.All patients were thoroughly evaluated preoperatively, intraoperatively, and postoperatively. Results: We hypothesized that in our patient cohort, warm blood cardioplegia could be as successful as or even better than the conventional antegrade cold blood cardioplegia. Patients were randomised into two similar blocks, each of which consisted of 100 patients, each of whom obtained one of the two cardioplegic solutions. Our analysis did not indicate a statistically important difference in the post-operative release of myocardial biomarkers (Troponin I) & CK in both classes. This finding did not significantly reflect the clinical outcome of our patient, which may indicate similar myocardial protection in primary low-risk CABG patients for both cold and warm blood cardioplegia. Conclusion: During the time of cardiac arrest, both methods tend to enable an equal and adequate approach for myocardial defence. To attain improved myocardial defence, warm blood cardioplegia needs a shorter administration interval. Therefore, the choice between one type of cardioplegia and the other remains at the discretion of the surgeon. The statistically minor variation found in the release of myocardial enzymes did not translate into distinct clinical results.

Transitioning to Del Nido cardioplegia for all-comers: the next switching gear?

BackgroundExclusive use of Del Nido cardioplegia administration in all adult patients undergoing cardiac surgery has been studied for operative, postoperative and myocardial protection outcomes.MethodsFrom November 2016 to October 2017, Del Nido cardioplegia was used in 131 consecutive patients (DN group). Using a propensity score, DN group was compared to 251 patients having received intermittent cold blood cardioplegia (CB group).ResultsPreoperative characteristics were similar in DN and CB groups. Operative outcomes were statistically different (p < 0.0001): cardiopulmonary bypass (CPB) time (DN 105.9 ± 46.5, CB 131.2 ± 38.8); aortic cross-clamp time (DN 80.8 ± 35.5, CB 102.2 ± 31.3); operative time (DN 203.1 ± 65.0, CB 241.5 ± 54.7); total cardioplegia volume (DN 1328 ± 879, CB 3773 ± 1226); and peak glycemia on CPB (DN 8.2 ± 2.3, CB 9.0 ± 1.8). No statistical differences were noted in intensive care unit stay, hospital stay and hospital death. Myocardial protection outcomes were similar: discharge left ventricular ejection fraction (DN 52 ± 11, CB 51 ± 10); Troponin levels at the end of the surgery (DN 871 ± 1623, CB 1958 ± 854), day 1 (DN 853 ± 1139, CB 993 ± 8234) and day 4 (DN 442 ± 540, CB 463 ± 317).ConclusionDel Nido cardioplegia use in all adult cardiac surgeries is associated with improved surgical efficiency. The design of larger trials including adults combined cardiac procedures and emergencies is needed.

Custodiol versus cold Calafiore for elective cardiac arrest in isolated aortic valve replacement: a propensity-matched analysis of 7263 patients.

This study was designed to assess the impact of crystalloid cardioplegia (CCP) and blood cardioplegia (BCP) on short- and long-term outcome after isolated aortic valve replacement (AVR). A total of 7263 patients undergoing AVR at our institution between November 1994 and June 2015 were identified. CCP (Custodiol ® ) was used in 83% ( n = 5998) and intermittent cold BCP in 1007 patients (14%). For 4790 patients, propensity scores were calculated from baseline data, risk factors, comorbidities and characteristics of the disease, resulting in 825 pairs. The primary outcome was operative mortality (OM). There was no significant difference in OM between CCP and BCP cohorts [33 of 825 (4.0%) vs 35 of 825 (4.2%), P = 0.90]. The incidence of postoperative complications was comparable between both groups. Long-term survival was also not different between CCP and BCP (log-rank test: P = 0.9). Multiple Cox regression analysis demonstrated that mortality was significantly affected by renal function ( P < 0.001), logistic EuroSCORE ( P < 0.001), male sex ( P = 0.005) and diabetes ( P = 0.037). Patients with reduced left ventricular ejection fraction ≤30% showed improved survival when receiving BCP intraoperatively [odds ratio: 2.28 (1.12-4.63); P = 0.03]. CCP and BCP provide equivalent outcome after isolated AVR. However, BCP seems to be beneficial for patients with reduced left ventricular ejection fraction.

Systemic Dosing of Thymosin Beta 4 before and after Ischemia Does Not Attenuate Global Myocardial Ischemia-Reperfusion Injury in Pigs.

The use of cardiopulmonary bypass (CPB) and aortic cross-clamping causes myocardial ischemia-reperfusion injury (I-RI) and can lead to reduced postoperative cardiac function. We investigated whether this injury could be attenuated by thymosin beta 4 (TB4), a peptide which has showed cardioprotective effects. Pigs received either TB4 or vehicle and underwent CPB and aortic cross-clamping for 60 min with cold intermittent blood-cardioplegia and were then followed for 30 h. Myocardial function and blood flow was studied by cardiac magnetic resonance and PET imaging. Tissue and plasma samples were analyzed to determine the amount of cardiomyocyte necrosis and apoptosis as well as pharmacokinetics of the peptide. In vitro studies were performed to assess its influence on blood coagulation and vasomotor tone. Serum levels of the peptide were increased after administration compared to control samples. TB4 did not decrease the amount of cell death. Cardiac function and global myocardial blood flow was similar between the study groups. At high doses a vasoconstrictor effect on mesentery arteries and a vasodilator effect on coronary arteries was observed and blood clot firmness was reduced when tested in the presence of an antiplatelet agent. Despite promising results in previous trials the cardioprotective effect of TB4 was not demonstrated in this model for global myocardial I-RI.

Abstract 18424: Elective Cardiac Arrest in Isolated Aortic Valve Surgery: Comparison of Blood-cardioplegia versus HTK-Bretschneider Solution in 7005 Consecutive Patients

Introduction: Assessing the impact of HTK-Bretschneider solution versus blood-cardioplegia on short- and long-term outcome after isolated aortic valve replacement (AVR). Hypothesis: HTK-Bretschneider is not inferior to Blood-cardioplegia for isolated aortic valve replacement. Methods: Screening of our institutional database revealed 7290 consecutive patients who underwent AVR between 11/1994 and 06/2015. In the majority of patients (n=5998; 83%) antegrade infusion of htk-bretschneider solution (custodiol®) was used for elective cardiac arrest (Group A). Intermittent cold blood-cardioplegia was chosen in 1007 patients (14%; Group B). All preoperative risk-factors were considered for risk-factor analysis influencing outcome. Results: Early mortality was equal between the subgroups (p=0.22). Postoperative complications like pacemaker implantation (p=0.01) or low cardiac output were more likely to occur in group B (p=0.02). Overall long term survival was inferior for patients receiving elective cardiac arrest with cold blood cardioplegia (p&lt;0.001). Cox-regression identified age (HR: 1.063 ; p&lt;0.001), end stage renal disease (ESDR; HR:4.8; p&lt;0.001), history of PCI (HR: 1.3; p=0.03), active infective endocarditis (AIE; HR: 2.1; p&lt;0.001), neurological dysfunction (HR: 1.4; p=0.02), low ejection fraction (EF&lt;30%; HR: 2.5; p&lt;0.001), prior cardiac surgery (HR:1,5; p=0.02) and emergent surgical intervention (HR: 2.5; p&lt;0.001) being highly associated with long term survival and occurring more frequently in group B. Artificial low-risk and high-risk groups showed no differences in longevity depending on cardioplegic solutions (p=0.35). Conclusions: Blood-cardioplegia for elective cardiac arrest seems to be preferred when complex aortic valve surgery is expected. However, HTK-Bretschneider solution yields equivalent longevity to blood-cardioplegia, even after surgery demanding extended cross-clamp times.

Endothelial Injury Associated with Cold or Warm Blood Cardioplegia during Coronary Artery Bypass Graft Surgery.

The aim of this investigation was to analyze the impact of intermittent cold blood cardioplegia (ICC) and intermittent warm blood cardioplegia (IWC) on endothelial injury in patients referred to elective on-pump coronary artery bypass graft (CABG) surgery. Patients undergoing CABG procedures were randomized to either ICC or IWC. Myocardial injury was assessed by CK-MB and cardiac troponin T (cTnT). Endothelial injury was quantified by circulating endothelial cells (CECs), von Willebrand factor (vWF), and soluble thrombomodulin (sTM). Perioperative myocardial injury (PMI) and major adverse cardiac events (MACE) were recorded. Demographic data and preoperative risk profile of included patients (ICC: n = 32, IWC: n = 36) were comparable. No deaths, PMI, or MACE were observed. Levels of CK-MB and cTnT did not show intergroup differences. Concentrations of CECs peaked at 6 h postoperatively with significantly higher values for IWC-patients at 1 h (ICC: 10.1 ± 3.9/mL; IWC: 18.4 ± 4.1/mL; P = 0.012) and 6 h (ICC: 19.3 ± 6.2/mL; IWC: 29.2 ± 6.7/mL; P < 0.001). Concentrations of vWF (ICC: 178.4 ± 73.2 U/dL; IWC: 258.2 ± 89.7 U/dL; P < 0.001) and sTM (ICC: 3.2 ± 2.1 ng/mL; IWC: 5.2 ± 2.4 ng/mL; P = 0.011) were significantly elevated in IWC-group at 1 h postoperatively. This study shows that the use of IWC is associated with a higher extent of endothelial injury compared to ICC without differences in clinical endpoints.

Intermittent cold-blood vs. warm-blood cardioplegia – a comparative study on myocardial acidosis during coronary bypass surgery

The aim of the study was to assess the impact of the intermittent cold-blood cardioplegia (ICBC) on myocardial acidosis in comparison to the warm-blood cardioplegic administration (IWBC) in patients undergoing coronary bypass surgery. In 15 patients undergoing elective bypass surgery with ICBC for myocardial protection, metabolic changes of global ischemia indicators with lactate and pH values, measured simultaneously in the arterial and coronary sinus blood, were analyzed and compared with those observed when warm-blood method was used. For comparison, the analysis of variance with repeated measurements including tests for a cross-over effect of group and time was used. In patients with ICBC compared to IWBC, the lactate production as well as degree of acidosis were generally lower with a significant group effect for both, lactate and pH values measured at the end of reperfusions. Our results suggest that ICBC has an inhibiting effect on potentially progressive myocardial acidosis during cross clamp period.

Myocardial Protection Era: From Valve Surgery to Heart Transplantation

Myocardial Protection Era: From Valve Surgery to Heart Transplantation

Circulating endothelial cells – a super-sensitive marker of myocardial injury indicating superior myocardial protection for intermittent cold versus warm blood cardioplegia in patients undergoing CABG surgery

Objectives: To investigate the impact of intermittent cold (ICC) and intermittent warm blood cardioplegia (IWC) on clinical outcomes, markers of myocardial and endothelial injury in patients referred to elective on-pump coronary artery bypass graft (CABG) surgery.

Myocardial protection with warm versus cold blood cardioplegia in patients with prolonged aortic cross-clamp times during isolated cardiac surgery

Objectives: To evaluate the cardioprotective effects of intermittent warm (IWC) versus intermittent cold blood cardioplegia (ICC) in patients referred to isolated cardiac coronary bypass grafting (CABG), aortic (AVR) or mitral valve procedures (MVR) that required prolonged periods of aortic clamping.

Cold blood vs. warm blood cardioplegia in patients with acute coronary syndrome undergoing coronary artery bypass grafting

Objective: Patients with acute coronary syndrome (ACS) undergoing urgent on-pump coronary artery bypass grafting (CABG) are at increased risk for myocardial ischemia/reperfusion injury, but the optimal cardioplegic strategy remains uncertain. This study compared the cardioprotective effects of intermittent warm (IWC) versus cold blood cardioplegia (ICC) in this high-risk cohort. Methods: All patients with acute coronary syndrome (ACS) and urgent indication for on-pump coronary artery bypass grafting (CABG) were prospectively enrolled into the study. Applied cardioplegic strategy (ICC/IWC) was left at the discretion of the surgeon. Groups were compared with regard to the release of markers for myocardial injury (CK-MB, cTnT) and clinical outcomes, including in-hospital mortality and major adverse cardiac events (MACE). Results: From April to September 2010 a total of 65 patients with ACS underwent urgent CABG in our institution. Mean patients age was 67.6±9.8 years. IWC was used in 20 patients (30.8%) while ICC was applied in 45 patients (69.2%). Demographics, intraoperative data (CPB time, cross-clamp time, number of grafts) did not differ between groups. Pre- and postoperative levels of myocardial injury markers (CK-MB, cTnT) were similar in both groups (p=ns). Overall in-hospital mortality was 12.3% (8/65) with a MACE rate of 21.5% (14/65) without intergroup differences. Conclusion: Urgent CABG for ACS is associated to an increased postoperative mortality and morbidity. Our preliminary analysis in this small patients cohort fails to reveal relevant benefits of either cold or warm blood cardioplegia for myocardial protection in this high-risk patients cohort.

Effect of Partial Oxygen Supply on Mitochondrial Electron Transport System During Complete Cardiac Ischemia

During complete ischemia we assessed myocardial utilization of the small amount of oxygen available. We also determined whether blood cardioplegia has any advantage over crystalloid cardioplegia in this setting. Patients with preserved left ventricular myocardial function and without anterolateral wall infarct or aneurysm were included to the study. Intermittent cold blood and crystalloid cardioplegia were used in 10 patients (group BC) and 9 patients (group CC), respectively. From myocardial biopsies, obtained before and after ischemia, complete electron transport system (ETS) enzyme activities (NDH, SDH, NCCR, SCCR, and COX) and lactate content were analyzed. Biochemical and hemodynamic analyses also were done. Myocardial and blood temperatures were monitored. Ischemic time was longer in group CC (p < 0.05). There were no important differences in biochemical and hemodynamic variables between the two groups. In addition, there was no difference in NDH and SDH activities as well as COX/SCCR and COX/RS-NCCR ratios between the two groups before and after ischemia. After Ischemia, RS-NCCR in group CC and SCCR and COX activities in both groups were lower than the control. For all enzymes, activity change ratios were not different between groups. Myocardial lactate content was increased in both groups after ischemia. However, the increase in group BC was less (p < 0.01). Based on our findings, we believe that the superiority of blood cardioplegia over crystalloid cardioplegia does not depend on oxygen content, but on other factors such as buffering and free oxygen radical scavenger effects among others. However, with the warm and continuous blood cardioplegia technique, oxygen content might be more important.

Surgery for Cardiac Valves and Aortic Root Without Cardioplegic Arrest ("Beating Heart"): Experience with a New Method of Myocardial Perfusion

Simultaneous antegrade/retrograde warm blood perfusion with a beating heart has not been previously reported as a mean of protecting hypertrophied hearts in cardiac valve and aortic root surgeries. Similarly, beating heart mitral valve surgery via the trans-septal approach with the aorta unclamped, is a novel technique. We, herein, report a series of 346 patients with a variety of cardiac pathologies who were operated upon utilizing a new modality of myocardial perfusion. Among this group of patients, there were 55 patients who were diagnosed with endocarditis of one or more valves. These patients were excluded from this series of patients. Mean age was 59 +/- 12, and there were 196 (67.3%) males and 95 (32.7%) females. There were six aortic root procedures, 90 mitral valve replacements (MVR), 46 mitral valve repairs, 20 MVR+ coronary artery bypass grafting (CABG), 28 tricuspid valve repairs, 106 aortic valve replacements (AVR), 17 AVR+CABG, and 8 AVR/MVR. Crude mortality for the group was 20 of 291 (6.8%). Intra-aortic balloon pump utilization at time of weaning from cardiopulmonary bypass was 6/291 (2.06%), and re-operation for bleeding was needed in 12 of 291 (4.1%) patients. Postoperative stroke occurred in 4 of 291 (1.3%) patients. In these patients, the clinical diagnosis of stroke was made prior to surgery. This initial experience with this new method of myocardial perfusion indicates that results are at least comparable, if not superior, to conventional techniques utilizing intermittent cold blood cardioplegia.

Evaluation by Cardiac Troponin I: The Effect of Ischemic Preconditioning as an Adjunct to Intermittent Blood Cardioplegia on Coronary Artery Bypass Grafting

Ischemic preconditioning (IPC) is commonly regarded as having a powerful internal protective effect on the organs. The mechanism of IPC is not clear yet, and the controversy over the benefits and protocol of IPC still continues. In this study, we used the sensitive and specific biochemical marker: cardiac troponin-I (CTnI) to evaluate whether IPC as an adjunct to intermittent cold blood cardioplegia (CBC) could reduce myocardial injury, as opposed to simple CBC during coronary artery bypass grafting (CABG). From May 2003 to December 2003, 40 patients with three vessel coronary artery disease (CAD) and stable angina, receiving first-time elective CABG, were randomly divided into two equal groups: IPC plus CBC (IPC + CBC group, n = 20); and CBC (CBC group, n = 20). The patients in IPC + CBC group received two cycles of ischemia (two min) and reperfusion (three min) before myocardial arrest induced by CBC. The patients in CBC group received 10-minute normothermic cardiopulmonary bypass (CPB) before CBC arrest. Clinical outcomes were observed during and after the operation. Serial venous blood samples were obtained before induction, after CPB, and postoperatively 6, 12, 24, and 72 hours. Hemodynamic indexes were obtained before and after the bypass by the radial catheter and Swan-Ganz catheter. In both groups, there were no differences regarding operative parameters. Compared to the baseline, the level of CTnI increased after CPB, peaked 6-12 hours (p < 0.01). Compared to IPC + CBC group, plasma concentrations of CTnI in CBC group were significantly higher at 6 and 12 hours (p < 0.05). CI recovery in IPC + CBC group was more significant than CBC group at 12 and 24 hours (p < 0.05). IPC + CBC also shortened the time of postoperative mechanical ventilation (p < 0.05) after surgery. Compared to the simple CBC in lower-risk CABG patients, IPC as an adjunct to CBC reduced CTnI release, improved heart function after surgery, and shortened the time of recovery in CAD patients.

Mitral valve surgery and acute renal failure

Mitral valve surgery and acute renal failure

Continuous Tepid Blood Cardioplegia Can Preserve Coronary Endothelium and Ameliorate the Occurrence of Cardiomyocyte Apoptosis

In modern cardiac surgery, crystalloid or blood cardioplegic solutions have been used widely for myocardial protection; however, ischemia does occur during protection with intermittent infusion of cold crystalloid or blood cardioplegic solutions. The present study was designed to evaluate the effect of different cardioplegic methods on myocardial apoptosis and coronary endothelial injury after global ischemia, cardiopulmonary bypass (CPB), and reperfusion in anesthetized open-chest dogs. The dogs were classified into five groups to identify the injury of myocardium and coronary endothelium: group 1, normothermic CPB without cardiac arrest; group 2, hypothermic CPB with continuous tepid blood cardioplegia, and with cardiac arrest; group 3, hypothermic CPB with intermittent cold blood cardioplegia, and with cardiac arrest; group 4, hypothermic CPB with intermittent cold crystalloid cardioplegia, and with cardiac arrest; and group 5, sham-operated control group. During CPB, cardiac arrest was achieved with different cardioplegia solutions for 60 min, followed by reperfusion for 4 h before the myocardium and coronary arteries were harvested. Coronary arteries were harvested immediately and analyzed by scanning electron microscopy. Cardiomyocytic apoptosis was detected using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling, Western blot, and DNA ladder methods. Regardless of the detection method used, significantly higher percentages of apoptotic cardiomyocytes were found in group 3 and group 4 than in other groups. Expression of caspase-3 correlated with increased apoptosis. Scanning electron microscopy revealed severe endothelial injury of coronary arteries in group 3 and group 4. These results point to an important explanation for the difference in cardiac recovery after hypothermic ischemia and arrest with various cardioplegic solutions.

Nitrotyrosine and 8-isoprostane formation indicate free radical-mediated injury in hearts of patients subjected to cardioplegia

Objective: Myocardial ischemia and reperfusion induced by cardioplegic arrest subjects the heart to free radical-mediated stress. The purpose of our study was to investigate the effect of cardioplegia-induced ischemia and reperfusion on myocardial formation and distribution of (1) nitrotyrosine as an indicator for peroxynitrite-mediated tissue injury resulting from increased nitric oxide release and (2) 8-isoprostane as an indicator for oxygen-derived free radical-mediated lipid peroxidation. Methods: In 10 patients undergoing coronary artery operations (64 ± 6 [mean ± SD] years, 3 women and 7 men) subjected to cardiopulmonary bypass and intermittent cold blood cardioplegia, we collected transmural left ventricular biopsy specimens before and at the end of cardiopulmonary bypass. Specimens were cut at 10 μm and subjected to immunocytochemical staining against the nitric oxide-producing enzyme constitutive nitric oxide synthase, cyclic guanosine monophosphate (intracellular second messenger of nitric oxide), nitrotyrosine, and 8-isoprostane by using polyclonal antibodies. For global left ventricular function determination, we measured the fractional area of contraction using transesophageal echocardiography. Results: Nitric oxide synthase activity in cardiac myocytes increased from 34 ± 10 gray units before cardiopulmonary bypass to 47 ± 12 gray units at the end of bypass (P =.015), and all hearts showed increased cyclic guanosine monophosphate content in both myocytes and endothelial cells at the end of bypass. The number of nitrotyrosine-positive capillaries increased from 36 ± 29/mm2 before bypass to 82 ± 47/mm2 at the end of bypass (P =.012), and 8-isoprostane-positive capillaries increased from 92 ± 72/mm2 before bypass to 209 ± 108/mm2 at the end of bypass (P =.005). The fractional area of contraction was 53% ± 12% before bypass and 56% ± 12% after bypass (P =.47) but was slightly decreased to 45% ± 14% at 4 hours after bypass (P =.121). Conclusions: Our data show that cardioplegia-induced myocardial ischemia and reperfusion is associated with nitrotyrosine and 8-isoprostane formation mainly in the coronary endothelium, indicating injury mediated by both peroxynitrite and oxygen-derived free radicals. Because nitric oxide synthase activation was accompanied with increased cyclic guanosine monophosphate, these data suggest that direct effects of nitric oxide on cardiac myocytes, as well as nitric oxide-mediated coronary endothelial injury, might contribute to injury associated with cardioplegia and cardiopulmonary bypass.J Thorac Cardiovasc Surg 2003;125:178-83

Aortic root reimplantation for successful repair of an insufficient pulmonary autograft valve after the Ross procedure

J Thorac Cardiovasc Surg 2002;124:1048-9