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1.
Heart Surg Forum ; 24(4): E619-E623, 2021 Jul 26.
Article in English | MEDLINE | ID: mdl-34473027

ABSTRACT

OBJECTIVES: Cardioplegia solutions have a role not only in arresting the heart but also in protecting the myocardium from ischemia. While antegrade cardioplegia is given by the heart-lung machine in many centers, it is given by a hand-squeezed bag in very few centers. The pressure of cardioplegia given antegrade from the heart-lung machine is certain (60-90 mmHg). The pressure applied in the cardioplegia method, which is given antegrade with a hand-squeezed bag, is uncertain and variable. We compared the antegrade cardioplegia method applied with a hand-squeezed bag with the antegrade cardioplegia method applied with a roller pump from the heart-lung machine in terms of protecting the myocardium from ischemia. METHODS: Seventy-six patients who did not have an acute myocardial infarction, had normal preoperative cardiac marker (troponin and CK-MB) values, did not undergo redo open heart surgery, had an ejection fraction of 50% and above, and underwent elective two or three-vessel isolated coronary artery bypass surgery were evaluated. While tepid (30-32°C) blood cardioplegia was administered antegrade to 33 patients (Group A) with a hand-squeezed bag, the other 34 patients (Group B) received tepid (30-32°C) antegrade blood cardioplegia from the heart-lung machine. The perioperative and postoperative data of the patients were recorded and compared. To evaluate myocardial damage, postoperative cardiac markers and echocardiography data were evaluated and compared at the fourth hour after the cross-clamp was removed in both groups. RESULTS: When evaluated in terms of preoperative demographic data, preoperative mean EF values and intraoperative data, there was no statistical difference between both groups. When we evaluated in terms of myocardial protection, the mean TnT level was 4.31 ± 1.95 at the 4th hour in Group A and 3.91 ± 1.69 in Group B. Mean 4th hour CK-MB level was 40.84 ± 9.07 in Group A and 38.56 ± 8.07 in Group B. Mean change in EF (%) was -4.09 ± 4.41 in Group A and 3.53 ± 4.53 in Group B. In line with the current data when we evaluated in terms of myocardial protection, we found that there is no statistical difference between the two groups (P = 0.373; P = 0.158; P = 0.523). There was no statistical difference between both groups, in terms of postoperative arrhythmias. None of the patients died, and no patients required an intra-aortic balloon pump. RESULTS: As a result of our study, cardioplegia administration with a certain constant pressure from the roller pump and hand-squeezed bag with uncertain pressure does not make a difference, in terms of myocardial protection. We think that the content and amount of cardioplegia and the preferred time for repeated cardioplegia applications are more important for the protection of the myocardium. METHODS: 76 patients who did not have an acute myocardial infarction, had normal preoperative cardiac marker (troponin and CK-MB) values, did not undergo redo open heart surgery, had an ejection fraction of 50% and above, and underwent elective two or three-vessel isolated coronary artery bypass surgery were evaluated. While tepid(30-32 ° C) blood cardioplegia was administered antegrade to 33 patients(Group A) with a hand-squeezed bag, the other 34 patients(Group B) received tepid(30-32 °C) antegrade blood cardioplegia from the heart-lung machine. The perioperative and postoperative data of the patients were recorded and compared. To evaluate myocardial damage, postoperative cardiac markers and echocardiography data were evaluated and compared at the fourth hour after the cross-clamp was removed in both groups. RESULTS: When evaluated in terms of preoperative demographic data, preoperative mean EF values and intraoperative data there was no statistical difference between both groups. When we evaluated in terms of myocardial protection, the mean TnT level was 4.31 ± 1.95 at the 4th hour in group A and 3.91 ± 1.69 in group B. Mean 4th hour CK-MB level was 40.84 ± 9.07 in group A and 38.56 ± 8.07 in group B. Mean change in EF (%) was -4.09 ± 4.41 in group A and 3.53 ± 4.53 in group B. In line with the current data when we evaluated in terms of myocardial protection; we found that there is no statistical difference between the two groups (p = 0.373; p = 0.158; p = 0.523). There was no statistical difference between both groups in terms of postoperative arrhythmia's. None of the patients died and none of the patients required an intra-aortic balloon pump.


Subject(s)
Cardioplegic Solutions/administration & dosage , Coronary Artery Bypass/methods , Heart Arrest, Induced/adverse effects , Heart Arrest, Induced/instrumentation , Aged , Arrhythmias, Cardiac/etiology , Coronary Artery Bypass/adverse effects , Coronary Disease/surgery , Female , Heart Arrest, Induced/methods , Humans , Male , Middle Aged , Postoperative Complications , Pressure
2.
J Card Surg ; 35(10): 2737-2746, 2020 Oct.
Article in English | MEDLINE | ID: mdl-33043657

ABSTRACT

BACKGROUND: Consensus on the optimum choice of cardioplegia remains elusive. One possibility that has been suggested to have beneficial properties is microplegia, a cardioplegia of reduced crystalloid volume. The aim of this meta-analysis is to comprehensively investigate microplegia against a range of clinical outcomes. METHODS: To identify potential studies, systematic searches were carried out in four databases (eg, Pubmed, EMBASE). The search strategy included the key concepts of "microplegia" OR "mini-cardioplegia" OR "miniplegia" AND "cardiac surgery." This was followed by a meta-analysis investigating: mortality, crystalloid volume; cardiopulmonary bypass time; cross-clamp time; intra-aortic balloon pump use; spontaneous heartbeat recovery; inotropic support; low cardiac output syndrome; myocardial infarction; acute renal failure; atrial fibrillation, reoperation for bleeding; creatine kinase myocardial band (CK-MB); intensive care unit (ICU) time and hospital stay. RESULTS: Eleven studies comprising 5798 participants were analyzed. Microplegia used a lower volume of crystalloids and led to a higher spontaneous return of heartbeat, odds ratio (OR) 4.271 (95% confidence intervals [CIs]: 1.935, 9.423; I2 = 76.57%; P < .001) and a lower requirement for inotropic support, OR: 0.665 (95% CI: 0.47, 0.941; I2 = 3.53%; P = .021). Microplegia was also associated with a lower CK-MB release, mean difference (MD) -6.448 ng/mL (95% CI: -9.386, -3.511; I2 = 0%; P < .001) and a shorter ICU stay, MD: -0.411 days (95% CI: -0.812, -0.009; I2 = 17.65%; P = .045). All other comparisons were nonsignificant. CONCLUSIONS: Microplegia has similar effects to other types of cardioplegia and is beneficial with regard to spontaneous return of heartbeat, inotropic support, ICU stay, and CK-MB release.


Subject(s)
Cardiac Surgical Procedures , Cardioplegic Solutions/administration & dosage , Heart Arrest, Induced/methods , Acute Kidney Injury , Cardiac Output, Low , Cardiopulmonary Bypass , Creatine Kinase, MB Form/metabolism , Heart Rate , Humans , Length of Stay , Myocardial Infarction , Operative Time , Postoperative Complications , Recovery of Function , Treatment Outcome
3.
BMC Cardiovasc Disord ; 20(1): 215, 2020 05 08.
Article in English | MEDLINE | ID: mdl-32384925

ABSTRACT

BACKGROUND: Exclusive use of Del Nido cardioplegia administration in all adult patients undergoing cardiac surgery has been studied for operative, postoperative and myocardial protection outcomes. METHODS: From 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). RESULTS: Preoperative 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). CONCLUSION: Del 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.


Subject(s)
Cardioplegic Solutions/administration & dosage , Electrolytes/administration & dosage , Heart Arrest, Induced , Lidocaine/administration & dosage , Magnesium Sulfate/administration & dosage , Mannitol/administration & dosage , Potassium Chloride/administration & dosage , Sodium Bicarbonate/administration & dosage , Solutions/administration & dosage , Aged , Cardioplegic Solutions/adverse effects , Electrolytes/adverse effects , Female , Heart Arrest, Induced/adverse effects , Heart Arrest, Induced/mortality , Humans , Length of Stay , Lidocaine/adverse effects , Magnesium Sulfate/adverse effects , Male , Mannitol/adverse effects , Middle Aged , Operative Time , Postoperative Complications/etiology , Potassium Chloride/adverse effects , Retrospective Studies , Sodium Bicarbonate/adverse effects , Solutions/adverse effects , Time Factors , Treatment Outcome
4.
J Am Heart Assoc ; 9(6): e012376, 2020 03 17.
Article in English | MEDLINE | ID: mdl-32151220

ABSTRACT

Background Laboratory studies demonstrate glucose-insulin-potassium (GIK) as a potent cardioprotective intervention, but clinical trials have yielded mixed results, likely because of varying formulas and timing of GIK treatment and different clinical settings. This study sought to evaluate the effects of modified GIK regimen given perioperatively with an insulin-glucose ratio of 1:3 in patients undergoing cardiopulmonary bypass surgery. Methods and Results In this prospective, randomized, double-blinded trial with 930 patients referred for cardiac surgery with cardiopulmonary bypass, GIK (200 g/L glucose, 66.7 U/L insulin, and 80 mmol/L KCl) or placebo treatment was administered intravenously at 1 mL/kg per hour 10 minutes before anesthesia and continuously for 12.5 hours. The primary outcome was the incidence of in-hospital major adverse cardiac events including all-cause death, low cardiac output syndrome, acute myocardial infarction, cardiac arrest with successful resuscitation, congestive heart failure, and arrhythmia. GIK therapy reduced the incidence of major adverse cardiac events and enhanced cardiac function recovery without increasing perioperative blood glucose compared with the control group. Mechanistically, this treatment resulted in increased glucose uptake and less lactate excretion calculated by the differences between arterial and coronary sinus, and increased phosphorylation of insulin receptor substrate-1 and protein kinase B in the hearts of GIK-treated patients. Systemic blood lactate was also reduced in GIK-treated patients during cardiopulmonary bypass surgery. Conclusions A modified GIK regimen administered perioperatively reduces the incidence of in-hospital major adverse cardiac events in patients undergoing cardiopulmonary bypass surgery. These benefits are likely a result of enhanced systemic tissue perfusion and improved myocardial metabolism via activation of insulin signaling by GIK. Clinical Trial Registration URL: clinicaltrials.gov. Identifier: NCT01516138.


Subject(s)
Cardiac Surgical Procedures , Cardioplegic Solutions/administration & dosage , Cardiopulmonary Bypass , Heart Arrest, Induced , Heart Diseases/surgery , Postoperative Complications/prevention & control , Adult , Cardiac Surgical Procedures/adverse effects , Cardioplegic Solutions/adverse effects , Cardiopulmonary Bypass/adverse effects , Cardiopulmonary Bypass/mortality , China , Coronary Circulation/drug effects , Double-Blind Method , Drug Administration Schedule , Energy Metabolism/drug effects , Female , Glucose/administration & dosage , Glucose/adverse effects , Heart Arrest, Induced/adverse effects , Heart Arrest, Induced/mortality , Heart Diseases/mortality , Hemodynamics/drug effects , Hospital Mortality , Humans , Infusions, Intravenous , Insulin/administration & dosage , Insulin/adverse effects , Male , Middle Aged , Myocardium/metabolism , Postoperative Complications/blood , Postoperative Complications/mortality , Postoperative Complications/physiopathology , Potassium/administration & dosage , Potassium/adverse effects , Prospective Studies , Risk Factors , Time Factors , Treatment Outcome
5.
Ann Thorac Surg ; 110(4): 1216-1224, 2020 10.
Article in English | MEDLINE | ID: mdl-32160958

ABSTRACT

BACKGROUND: Microplegia has been studied during isolated coronary artery bypass grafting and valve surgery but not in more complex operations. Objectives of this study were to demonstrate safety and effectiveness of microplegia relative to Buckberg cardioplegia during these operations. METHODS: From January 2012 to January 2017, 242 patients underwent multicomponent operations with simplified microplegia delivered via syringe pump and 10,512 with modified Buckberg cardioplegia. Operations included aortic root, arch, or ascending aorta replacement in 424 (94%) patients, aortic valve surgery in 324 (72%) patients, and concomitant coronary artery bypass grafting in 47 (10%) patients. Outcomes were compared in 226 propensity-matched pairs. RESULTS: There was no difference in median postoperative troponin T between groups after adjusting for aortic clamp time. Microplegia patients received significantly less crystalloid with their cardioplegia (mean 27 ± 8.0 mL/operation vs 735 ± 357 mL/operation; P < .001) and had lower peak intraoperative glucose (196 ± 40 mg/dL vs 248 ± 69 mg/dL; P < .001). Microplegia and Buckberg groups had similar in-hospital mortality (2.7% [n = 6] vs 2.2% [n = 5]; P = .8), stroke (2.2% [n = 5] vs 3.6% [n = 8]; P = .4), renal failure (8% [n = 18] vs 5.8% [n = 13]; P = .4), prolonged ventilation (23% [n = 51] vs 24% [n = 54]; P = .7), median postoperative length of stay (both 8.1 days; P > .9), and median red cell units administered to patients requiring transfusion (4 units vs 3 units; P = .14). The mean cost of cardioplegia per case with microplegia was 1/26th that of Buckberg cardioplegia. CONCLUSIONS: Our simplified microplegia technique offers several advantages over Buckberg cardioplegia without compromising myocardial protection or safety in complex, multicomponent operations with extended aortic clamp times.


Subject(s)
Cardiac Surgical Procedures/economics , Cost Savings , Health Care Costs , Heart Arrest, Induced/methods , Postoperative Complications/epidemiology , Aged , Cardiac Surgical Procedures/adverse effects , Cardioplegic Solutions/administration & dosage , Cardiopulmonary Bypass , Female , Heart Arrest, Induced/economics , Hospital Mortality , Humans , Male , Middle Aged , Postoperative Complications/blood , Propensity Score , Retrospective Studies , Treatment Outcome , Troponin T/blood
6.
Heart Lung Circ ; 29(2): 301-307, 2020 Feb.
Article in English | MEDLINE | ID: mdl-30723044

ABSTRACT

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Subject(s)
Cardioplegic Solutions/administration & dosage , Coronary Artery Bypass , Heart Arrest, Induced , Myocardium , Adult , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies
7.
J Thorac Cardiovasc Surg ; 160(5): 1195-1202.e12, 2020 Nov.
Article in English | MEDLINE | ID: mdl-31590948

ABSTRACT

OBJECTIVE: To compare outcomes of single (intervention group: del Nido [DN], and histamine-tryptophan-ketoglutarate) versus multidose (control group) cardioplegia in the adult cardiac surgery patients. METHODS: Medical search engines were interrogated to identify relevant randomized controlled trials and propensity-score matched cohorts. Meta-analysis was conducted for primary (in-hospital/30-day mortality) and secondary (ischemic and cardiopulmonary bypass [CPB] times, reperfusion fibrillation, peak of cardiac enzymes, myocardial infarction) endpoints. Subgroup analyses were conducted for study design and type of intervention, and meta-regression for primary outcome included type of surgery and left ventricular ejection fraction as moderators. RESULTS: Ten randomized controlled trials and 13 propensity-score matched cohorts were included, reporting on 5516 patients. Estimates are expressed as (parameter value [OR, odds ratio; MD, mean difference; SMD, standardized mean difference]/unit of measure [95% confidence interval], P value). DN reduced ischemic time (MD, -7.18 minutes [-12.52 to -1.84], P < .01), CPB time (MD, -10.44 minutes [-18.99 to -1.88], P .01), reperfusion fibrillation (OR, 0.16 [0.05-0.54], P < .01), and cardiac enzymes (SMD -0.17 [-0.29, 0.05], P < .01) compared with multidose cardioplegia. None of these beneficial effects were reproduced by histamine-tryptophan-ketoglutarate, which instead increased CPB time (MD, 2.04 minutes [0.73-3.37], P < .01) and reperfusion fibrillation (OR, 1.80 [1.20-2.70], P < .01). There was no difference in mortality and myocardial infarction between single and multidose, independently of type of surgery or left ventricular ejection fraction. CONCLUSIONS: DN decreases operative times, reperfusion fibrillation, and surge of cardiac enzymes compared with multidose cardioplegia.


Subject(s)
Cardioplegic Solutions , Heart Arrest, Induced , Aged , Cardiac Surgical Procedures , Cardioplegic Solutions/administration & dosage , Cardioplegic Solutions/therapeutic use , Cardiopulmonary Bypass , Female , Heart Arrest, Induced/methods , Heart Arrest, Induced/mortality , Humans , Male , Middle Aged , Operative Time , Propensity Score , Randomized Controlled Trials as Topic
8.
Thorac Cardiovasc Surg ; 68(3): 223-231, 2020 04.
Article in English | MEDLINE | ID: mdl-31022735

ABSTRACT

BACKGROUND: The aim of this study is to compare the combined use of the Myocardial Protection System and our microplegia (Basel Microplegia Protocol) with Cardioplexol® in coronary artery bypass grafting using the minimal extracorporeal circulation. METHODS: The analysis focused on propensity score matched pairs of patients in whom microplegia or Cardioplexol® was used. Primary efficacy endpoints were high-sensitivity cardiac troponin-T on postoperative day 1 and peak values during hospitalization. Furthermore, we assessed creatine kinase and creatinine kinase-myocardial type, as well as safety endpoints. RESULTS: A total of 56 patients who received microplegia and 155 patients who received Cardioplexol® were included. The use of the microplegia was associated with significantly lower geometric mean (confidence interval) peak values of high-sensitivity cardiac troponin-T (233 ng/L [194-280 ng/L] vs. 362 ng/L [315-416 ng/L]; p = 0.001), creatinine kinase (539 U/L [458-633 U/L] vs. 719 U/L [645-801 U/L]; p = 0.011), and creatinine kinase-myocardial type (13.8 µg/L [9.6-19.9 µg/L] vs. 21.6 µg/L [18.9-24.6 µg/L]; p = 0.026), and a shorter length of stay on the intensive care unit (1.5 days [1.2-1.8 days] vs. 1.9 days [1.7-2.1 days]; p = 0.011). Major adverse cardiac and cerebrovascular events occurred with roughly equal frequency (1.8 vs. 5.2%; p = 0.331). CONCLUSIONS: The use of the Basel Microplegia Protocol was associated with lower peak values of high-sensitivity cardiac troponin-T, creatinine kinase, and creatinine kinase-myocardial type and with a shorter length of stay on the intensive care unit, as compared with the use of Cardioplexol® in isolated coronary artery bypass surgery using minimal extracorporeal circulation.


Subject(s)
Cardioplegic Solutions/administration & dosage , Cardiopulmonary Bypass , Coronary Artery Bypass , Heart Arrest, Induced/methods , Myocardial Reperfusion Injury/prevention & control , Aged , Biomarkers/blood , Cardioplegic Solutions/adverse effects , Cardiopulmonary Bypass/adverse effects , Coronary Artery Bypass/adverse effects , Creatine Kinase, MB Form/blood , Female , Heart Arrest, Induced/adverse effects , Humans , Intensive Care Units , Length of Stay , Male , Middle Aged , Myocardial Reperfusion Injury/blood , Myocardial Reperfusion Injury/diagnosis , Myocardial Reperfusion Injury/etiology , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Troponin T/blood
9.
J Thorac Cardiovasc Surg ; 159(5): 1857-1863.e1, 2020 05.
Article in English | MEDLINE | ID: mdl-31204129

ABSTRACT

OBJECTIVE: The present prospective noninferiority randomized trial was designed to demonstrate the safety and efficacy of a single dose of Custodiol histidine-tryptophan-ketoglutarate compared with repetitive cold-blood cardioplegia. METHODS: From October 2012 to May 2014, 110 patients were randomly assigned to 1 of 2 groups: Group 1 (55 patients) received repetitive cold-blood cardioplegia, and group 2 (55 patients) received single-dose Custodiol histidine-tryptophan-ketoglutarate. Isolated aortic valve replacement, isolated mitral valve replacement, and multivalve procedures represented the most frequent operations, with 39 cases (71%) in group 1 and 49 cases (89%) in group 2. There was no difference in cardiopulmonary bypass time (102 ± 26 minutes vs 99 ± 19 minutes, P = .70) or aortic crossclamp time (77 ± 19 minutes vs 74 ± 17 minutes, P = .33). All patients underwent preoperative electrocardiogram and determination of creatine kinase-MB, troponin I, left ventricular ejection fraction, and regional wall motion. Postoperative cardiac biomarkers were checked at 7, 24, and 48 hours, and an echocardiogram was obtained to check for left ventricular function abnormalities. RESULTS: There was no difference in cardiac biomarkers release between the 2 groups at baseline and 7, 24, and 48 hours postoperatively (creatine kinase, P = .18, troponin P = .23). Left ventricular function was similar between groups preoperatively and at 24 hours after surgery. No death or myocardial infarction was observed in either group. There were no differences in intensive care unit length of stay, incidence of atrial fibrillation, use of inotropes or vasopressors support, time of intubation, or creatinine levels. CONCLUSIONS: A single dose of Custodiol histidine-tryptophan-ketoglutarate cardioplegia is not inferior to repeated cold-blood cardioplegia during elective cardiac surgery.


Subject(s)
Cardioplegic Solutions/administration & dosage , Heart Arrest, Induced/methods , Heart/physiology , Aged , Cardioplegic Solutions/adverse effects , Cardioplegic Solutions/therapeutic use , Creatine Kinase, MB Form/blood , Female , Glucose/administration & dosage , Glucose/adverse effects , Glucose/therapeutic use , Hemodynamics/physiology , Humans , Length of Stay , Male , Mannitol/administration & dosage , Mannitol/adverse effects , Mannitol/therapeutic use , Middle Aged , Postoperative Complications , Potassium Chloride/administration & dosage , Potassium Chloride/adverse effects , Potassium Chloride/therapeutic use , Procaine/administration & dosage , Procaine/adverse effects , Procaine/therapeutic use , Prospective Studies , Troponin I/blood
10.
J Thorac Cardiovasc Surg ; 159(6): 2275-2283.e1, 2020 06.
Article in English | MEDLINE | ID: mdl-31358336

ABSTRACT

OBJECTIVES: To compare the cardioprotective efficacy of a solution that requires only a single infusion at the start of the ischemic duration versus a solution that requires multiple infusions. METHODS: Aortic valve replacement was performed for 150 patients, who were randomized into the del Nido (DN) cardioplegia group or the cold blood (CB) cardioplegia group. The DN cardioplegia was delivered every 90 minutes and the CB cardioplegia was delivered every 20 to 30 minutes, or whenever cardiac activity was observed. The primary endpoints were electrical cardiac activity during crossclamp, ventricular fibrillation during reperfusion, and postoperative troponin and creatine kinase (CK-MB isoenzyme) at 24 and 48 hours. RESULTS: Electrical activity during crossclamp occurred in 29 (39.7%) patients in the DN group versus 34 (45.3%) patients in the CB group (adjusted P = 1.0). The number of procedures with ventricular fibrillation after removing the crossclamp was 41 (54.7%) in the CB group versus 17 (22.7%) in the DN group (adjusted P = .001; relative risk, 2.41). Troponin values appeared to be lower in the DN group (median, 223.10; interquartile range, 168.35-364.77 pg/mL vs 285.5; 196.20-419.45 pg/mL at 24 hours and 159.60; 125.42-217.20 pg/mL vs 201.60; 160.62-268.45 pg/mL at 48 hours) and CK-MB (median, 14.94; interquartile range, 12.16-20.39 ng/mL vs 17.43; 13.66-22.43 ng/mL at 24 hours and 6.19; 4.41-7.63 ng/mL vs 7.38; 4.74-10.20 ng/mL at 48 hours), but no significance was found. CONCLUSIONS: The del Nido cardioplegia protocol is an acceptable alternative for cold blood cardioplegia in patients undergoing aortic valve replacement.


Subject(s)
Aortic Valve/surgery , Cardioplegic Solutions/administration & dosage , Cold Temperature , Heart Arrest, Induced , Heart Valve Prosthesis Implantation , Aged , Aortic Valve/diagnostic imaging , Aortic Valve/physiopathology , Biomarkers/blood , Cardioplegic Solutions/adverse effects , Cold Temperature/adverse effects , Constriction , Creatine Kinase, MB Form/blood , Drug Administration Schedule , Female , Heart Arrest, Induced/adverse effects , Heart Valve Prosthesis Implantation/adverse effects , Humans , Male , Middle Aged , Poland , Time Factors , Treatment Outcome , Troponin/blood , Ventricular Fibrillation/etiology
11.
J Thorac Cardiovasc Surg ; 160(6): 1479-1485.e5, 2020 Dec.
Article in English | MEDLINE | ID: mdl-31706553

ABSTRACT

BACKGROUND: Del Nido cardioplegia (DC) offers prolonged single-dose myocardial protection in pediatric cardiac surgery. We set out to evaluate the efficacy of DC in adult patients undergoing isolated coronary artery bypass grafting (CABG). METHODS: From January 2012 to October 2017, 851 consecutive isolated CABG surgeries were performed by 2 study surgeons at our center with blood cardioplegia (BC, n = 350), used from January 2012 to April 2014, and DC (n = 501), used from May 2014 to October 2017. Propensity matching was used to yield 325 well-matched pairs. Clinical data were extracted from our local Society of Thoracic Surgeons database and mortality data from the Michigan State Social Security Death Index. RESULTS: Single-dose administration was used in 83% (417/501) of patients receiving DC. In propensity-matched groups, postoperative median troponin T levels (0.28 [0.16-0.59] ng/mL vs 0.46 [0.27-0.81] ng/mL; P < .01) were lower for patients receiving DC, and no difference in ejection fraction on postoperative echocardiography was observed (54 ± 12% and 53 ± 13% for BC and DC, respectively; P = .36). Perioperative outcomes were similar except for greater rate of atrial fibrillation (33% vs 23%; P = .01) in the DC group. Subgroup analyses revealed equivalent myocardial protection and clinical outcomes in patients with age ≥75 years, left ventricular ejection fraction ≤35%, left main disease, or Society of Thoracic Surgeons score ≥2.5%. Four-year survival did not differ between patients undergoing BC or DC. CONCLUSIONS: The current study revealed noninferior myocardial protection and clinical outcomes with DC versus BC in both routine and greater-risk patients undergoing isolated CABG. DC demonstrated the feasibility of single-dose administration for isolated CABG surgery. Larger randomized studies are needed to further explore the safety and efficacy of DC in adult cardiac surgery with longer crossclamp times.


Subject(s)
Coronary Artery Bypass/methods , Coronary Artery Disease/surgery , Heart Arrest, Induced/methods , Postoperative Complications/prevention & control , Aged , Cardioplegic Solutions/administration & dosage , Coronary Artery Disease/diagnosis , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Humans , Male , Postoperative Complications/mortality , Retrospective Studies , Survival Rate/trends , Treatment Outcome , United States/epidemiology
12.
Gen Thorac Cardiovasc Surg ; 68(6): 578-584, 2020 Jun.
Article in English | MEDLINE | ID: mdl-31707553

ABSTRACT

BACKGROUND: Hyperkalemic cardioplegia using St. Thomas' Hospital solution No. 2 (STH2) is commonly used to protect the myocardium during surgery. Mice deficient in the myocyte channel aquaporin 7 (AQP7) show significantly reduced glycerol and ATP contents and develop obesity; however, the influence of AQP7 on cardioplegia effectiveness remains unclear. METHODS: After determining the influence of ischemic duration on cardiac function, isolated hearts of male wild-type (WT) and AQP7-knockout (KO) mice (> 13 weeks old) were aerobically Langendorff-perfused with bicarbonate buffer, and randomly allocated to the control group (25 min of global ischemia) and STH2 group (5 min of STH2 infusion before 20 min of global ischemia, followed by 60 min of reperfusion). RESULTS: Final recovery of left ventricular developed pressure (LVDP) of WT and AQP7-KO hearts in the control group was 24.5 ± 12.4% and 20.6 ± 8.4%, respectively, which were significantly lower than those of the STH2 group (96.4 ± 12.7% and 92.9 ± 27.6%). Troponin T levels of WT and AQP-KO hearts significantly decreased in the STH2 groups (142.9 ± 27.2 and 219.9 ± 197.3) compared to those of the control (1725.0 ± 768.6 and 1710 ± 819.9). CONCLUSIONS: AQP7 was not involved in the protective efficacy of STH2 in this mouse model, suggesting its clinical utility even in complications of metabolic disease.


Subject(s)
Aquaporins/genetics , Cardioplegic Solutions/administration & dosage , Heart Arrest, Induced , Myocardial Reperfusion Injury/prevention & control , Animals , Female , Heart Ventricles/physiopathology , Hyperkalemia/chemically induced , Male , Mice , Mice, Knockout , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/physiopathology , Myocardium/metabolism , Random Allocation , Troponin T/metabolism
13.
J Card Surg ; 34(11): 1387-1389, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31449689

ABSTRACT

Myocardial protection during heart transplantation is achieved by a first dose of heart preservation solution during donor heart harvesting, while there is no consensus about the management of complementary doses during implantation in the recipient. We describe a preliminary case series where modified Del Nido Cardioplegia was used as complementary dose at the time of donor heart implantation.


Subject(s)
Cardioplegic Solutions/administration & dosage , Heart Arrest, Induced/methods , Heart Transplantation , Humans
14.
Ann Thorac Cardiovasc Surg ; 25(6): 296-303, 2019 Dec 20.
Article in English | MEDLINE | ID: mdl-31308305

ABSTRACT

PURPOSE: In this study, we aimed to assess myocardial protection and ischemia-reperfusion injury in patients undergoing open heart surgery with isothermic blood cardioplegia (IBC) or hypothermic blood cardioplegia (HBC). MATERIALS AND METHODS: A total of 48 patients who underwent isolated coronary artery bypass grafting or isolated mitral valve surgery between March 2017 and October 2017 were evaluated as randomized prospective study. Study groups (HBC: Group 1, IBC: Group 2) were compared in terms of interleukin 6 (IL-6), IL-8, IL-10, and complement factor 3a (C3a) levels, metabolic parameters, creatine kinase-muscle/brain (CK-MB) and high-sensitivity Troponin I (hsTn-I), and clinical outcomes. RESULTS: Comparison of the markers of ischemia-reperfusion injury showed significantly higher levels of the proinflammatory cytokine IL-6 in the early postoperative period as well as IL-8, in Group 2 (p <0.001), whereas the anti-inflammatory cytokine IL-10 was significantly higher during the X1 time period (p = 0.11) in Group 2, and subsequently it was higher in Group 1. Using myocardial temperature probes, the target myocardial temperatures were measured in the patients undergoing open heart surgery with different routes of cardioplegia, and significant differences were noted (p = 0.000). CONCLUSION: HBC for open heart surgery is associated with less myocardial injury and intraoperative and postoperative morbidity, indicating superior myocardial protection versus IBC.


Subject(s)
Cardiac Surgical Procedures/adverse effects , Cardioplegic Solutions/administration & dosage , Cardiopulmonary Bypass/adverse effects , Cold Temperature , Heart Arrest, Induced/methods , Myocardial Reperfusion Injury/prevention & control , Aged , Biomarkers/blood , Cardiac Surgical Procedures/mortality , Cardioplegic Solutions/adverse effects , Cardiopulmonary Bypass/mortality , Cytokines/blood , Female , Heart Arrest, Induced/adverse effects , Heart Arrest, Induced/mortality , Humans , Inflammation Mediators/blood , Male , Middle Aged , Myocardial Reperfusion Injury/blood , Myocardial Reperfusion Injury/etiology , Myocardial Reperfusion Injury/mortality , Prospective Studies , Risk Factors , Time Factors , Treatment Outcome , Turkey
15.
J Trauma Acute Care Surg ; 87(1): 68-75, 2019 07.
Article in English | MEDLINE | ID: mdl-30985476

ABSTRACT

BACKGROUND: Adenosine, lidocaine, and magnesium (ALM) is a cardioplegic agent shown to improve survival by improving cardiac function, tissue perfusion, and coagulopathy in animal models of shock. We hypothesized prehospital ALM treatment in hemorrhagic shock would improve survival compared to current Tactical Combat Casualty Care (TCCC) resuscitation beyond the golden hour. METHODS: Swine were randomized to: (1) TCCC, (2) 2 mL·kg vehicle control (VC), (3) 2 mL·kg ALM + drip, (4) 4 mL·kg ALM + drip, 5) 4 mL·kg ALM + delayed drip at 0.5 mL·kg·h, 6) 4 mL/kg VC, 7) 4 mL·kg ALM for 15 minutes + delayed drip at 3 mL·kg·h. Animals underwent pressure controlled hemorrhage to mean arterial pressure (MAP) of 30 mm Hg (S = 0). Treatment was administered at T = 0. After 120 minutes of simulated prehospital care (T = 120) blood product resuscitation commenced. Physiologic variables were recorded and laboratories were drawn at specified time points. RESULTS: Tactical Combat Casualty Care demonstrated superior survival to all other agents. The VC and ALM groups had lower MAPs and systolic blood pressures compared with TCCC. Except for the VC groups, lactate levels remained similar with correction of base deficit after prehospital resuscitation in all groups. Kidney function and liver function remained comparable across all groups. Compared with baseline values, TCCC demonstrated significant hypocoagulability. CONCLUSION: Adenosine, lidocaine, and magnesium, as administered in this study, are inferior to current Hextend-based resuscitation for survival from prolonged hemorrhagic shock in this model. In survivors, ALM groups had lower systolic blood pressures and MAPs, but provided a protective effect on coagulopathy as compared to TCCC. Adenosine, lidocaine, and magnesium do not appear to be a suitable low volume replacement to current TCCC resuscitation. The reduced coagulopathy compared to TCCC warrants future studies of ALM, perhaps as a therapeutic adjunct.


Subject(s)
Adenosine/therapeutic use , Cardioplegic Solutions/therapeutic use , Emergency Medical Services/methods , Lidocaine/therapeutic use , Magnesium/therapeutic use , Military Medicine/methods , Resuscitation/methods , Shock, Hemorrhagic/therapy , Wounds and Injuries/therapy , Adenosine/administration & dosage , Animals , Cardioplegic Solutions/administration & dosage , Disease Models, Animal , Lidocaine/administration & dosage , Magnesium/administration & dosage , Male , Resuscitation/mortality , Shock, Hemorrhagic/mortality , Swine , Wounds and Injuries/mortality
16.
Perfusion ; 34(6): 495-502, 2019 09.
Article in English | MEDLINE | ID: mdl-30848697

ABSTRACT

BACKGROUND: Myocardial protection in Tetralogy of Fallot patients undergoing intracardiac repair is suboptimal due to hypertrophied right ventricle. Hypertrophied myocardium is more susceptible to poor myocardial preservation because of inadequate capillary density as compared to the myocytes. There is a capillary to myocyte ratio mismatch. But del Nido Cardioplegia owing to its less viscosity is able to get more evenly distributed under hypothermic cardiopulmonary bypass as opposed to blood Cardioplegia. We hypothesized that the del Nido Cardioplegia technique, would be beneficial in myocardial protection because of its composition and method of delivery, leading into better early and late clinical outcomes in patients undergoing Tetralogy of Fallot repair as compared to blood cardioplegia reconstituted using St Thomas Cardioplegia solution. The objective of the study was to identify a better technique of myocardial preservation in Tetralogy of Fallot patient. METHODS: In total, 56 Tetralogy of Fallot patients undergoing intracardiac repair under mild hypothermic cardiopulmonary bypass were randomly allocated to receive antegrade Cardioplegia with either standard blood Cardioplegia (Group I) or del Nido Cardioplegia (Group II). Preoperative as well as postoperative data including echocardiographic parameters for right ventricle functions, creatine kinase MB level, inotropic requirement, mechanical ventilation duration, intensive care unit stay and hospital mortality were evaluated. RESULTS: Inotropic score in the first 24 hours postoperatively was significantly lower in Group II compared to Group I (13.4 ± 7.2 vs. 21.2 ± 9.6, p = 0.003). Creatine kinase MB level (ng/mL) was comparable between the groups. Echocardiographic parameters for right ventricle functions were also comparable between the groups during early as well as after 3 to 6 months postoperatively. CONCLUSION: Del Nido Cardioplegia is equally efficacious in providing myocardial protection during intracardiac repair under mild hypothermic cardiopulmonary bypass in Tetralogy of Fallot patients as compared to blood Cardioplegia solution with the added benefit of reducing inotropic requirement in first 24 hours postoperative period.


Subject(s)
Cardioplegic Solutions/administration & dosage , Cardiopulmonary Bypass , Heart Arrest, Induced , Tetralogy of Fallot , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Tetralogy of Fallot/blood , Tetralogy of Fallot/physiopathology , Tetralogy of Fallot/surgery
17.
J Cardiothorac Vasc Anesth ; 33(5): 1197-1204, 2019 May.
Article in English | MEDLINE | ID: mdl-30655202

ABSTRACT

OBJECTIVE: To compare myocardial protection with retrograde cardioplegia alone with antegrade and retrograde cardioplegia in minimally invasive mitral valve surgery (MIMS). DESIGN: Retrospective study. SETTING: Tertiary care university hospital. PARTICIPANTS: The authors studied 97 MIMS patients using retrograde cardioplegia alone and 118 MIMS patients using antegrade and retrograde cardioplegia. INTERVENTIONS: The data from patients admitted for MIMS using retrograde cardioplegia (MIMS retro) between 2009 to 2012 were compared with the data from patients undergoing MIMS with antegrade and retrograde cardioplegia (MIMS ante-retro) between 2006 and 2010 (control group). Cardioplegia in the MIMS retro group was delivered solely through an endovascular coronary sinus (CS) catheter positioned under echographic and fluoroscopic guidance. Antegrade and retrograde cardioplegia was used in the MIMS ante-retro group. Data regarding myocardial infarction (MI; creatine kinase Mb, troponin T, electrocardiogram), myocardial function, and hemodynamic stability were collected for comparison. MEASUREMENTS AND MAIN RESULTS: Adequate cardioplegia administration (CS pressure >30 mmHg and asystole) was attained in 74.2% of the patients with retrograde cardioplegia alone. In 23.7% of the patients, the addition of an antegrade cardioplegia was necessary. No difference was observed in the incidence of MI (0 MIMS retro v 1 for MIMS ante-retro, p = 0.3623), difficult separation from cardiopulmonary bypass, and postoperative malignant arrhythmia. No difference was found for maximal creatine kinase Mb (39.1 [28.0-49.1] v 37.9 [28.6-50.9]; p = 0.8299) and for maximal troponin T levels (0.39 [0.27-0.70] v 0.47 [0.32-0.79]; p = 0.1231) for MIMS retro and MIMS ante-retro, respectively. However, lactate levels in the MIMS retro group were significantly lower than in the MIMS ante-retro group (2.1 [1.4-3.05] v 2.4 [1.8-3.3], respectively; p = 0.0453). No difference was observed in duration of intensive care unit stay and death. MIMS retro patients had a shorter hospital stay (7.0 [6.0-8.0] v 8.0 [7.0-9.0] days; p = 0.0003). CONCLUSION: Retrograde cardioplegia administration alone provided comparable myocardial protection to antegrade and retrograde cardioplegia during MIMS, but was not sufficient to achieve asystole in one-fifth of patients.


Subject(s)
Cardiac Catheterization/methods , Coronary Sinus/surgery , Endovascular Procedures/methods , Heart Arrest, Induced/methods , Minimally Invasive Surgical Procedures/methods , Mitral Valve/surgery , Adult , Aged , Cardiac Catheterization/standards , Cardioplegic Solutions/administration & dosage , Combined Modality Therapy/methods , Combined Modality Therapy/standards , Endovascular Procedures/standards , Female , Heart Arrest, Induced/standards , Humans , Male , Middle Aged , Minimally Invasive Surgical Procedures/standards , Retrospective Studies
18.
Thorac Cardiovasc Surg ; 67(6): 484-487, 2019 Sep.
Article in English | MEDLINE | ID: mdl-30071564

ABSTRACT

We studied myocardial protection during coronary artery bypass graft surgery using low-volume cardioplegia (Cardioplexol) and minimal extracorporeal circulation (MECC) for different types of coronary artery diseases. In total, 426 consecutive patients were included and divided into four groups: those with left main stem stenosis (n = 45), those with three-vessel disease (n = 200), those with both (n = 141), and those with neither (n = 40). The peak postoperative myocardial markers and 30-day mortality were analyzed. Both myocardial markers and 30-day mortality were significantly elevated in patients with isolated main stem stenosis. We conclude that the use of low-volume cardioplegia and MECC is safe. However, patients with underlying isolated left main stem stenosis might be less protected.


Subject(s)
Cardioplegic Solutions/administration & dosage , Coronary Artery Bypass , Coronary Stenosis/surgery , Extracorporeal Circulation/methods , Heart Arrest, Induced/methods , Myocardial Reperfusion Injury/prevention & control , Potassium Compounds/administration & dosage , Biomarkers/blood , Cardioplegic Solutions/adverse effects , Coronary Artery Bypass/adverse effects , Coronary Artery Bypass/mortality , Coronary Stenosis/blood , Coronary Stenosis/diagnostic imaging , Coronary Stenosis/mortality , Creatine Kinase, MB Form/blood , Databases, Factual , Extracorporeal Circulation/adverse effects , Extracorporeal Circulation/mortality , Female , Heart Arrest, Induced/adverse effects , Heart Arrest, Induced/mortality , Humans , Male , Myocardial Reperfusion Injury/blood , Myocardial Reperfusion Injury/diagnosis , Myocardial Reperfusion Injury/mortality , Potassium Compounds/adverse effects , Risk Factors , Time Factors , Treatment Outcome , Troponin T/blood
19.
Thorac Cardiovasc Surg ; 67(6): 475-483, 2019 Sep.
Article in English | MEDLINE | ID: mdl-30049018

ABSTRACT

BACKGROUND: Crystalloid priming is a cost-effective, free from immunological reactions, and independent from human plasma delivery. However, there is some debate on the negative impact of low plasma colloid pressure and higher incidence of systemic inflammatory response syndrome (SIRS). The aim of the study was to rule out any adverse effects of crystalloid priming on the postoperative outcome. METHODS: We investigated 520 consecutive patients, including emergencies, who had isolated on-pump coronary artery bypass grafting in 2009 by retrospective analysis in our clinic. Crystalloid priming (n = 294) was introduced as an alternative to albumin (n = 226). Reviewing patient charts and IT-based data generated a dataset of perioperative parameters. RESULTS: There were no differences with respect to demographical data and preexisting comorbidities between both groups. Despite equal perfusion times, more volume had to be substituted during extracorporeal circulation following crystalloid priming. However, this did not influence the inhospital outcomes. According to the definition of the "Sepsis-3 Guidelines," the incidence of SIRS was similar. There was no difference in the need for a vasopressor treatment, and only transient higher serum lactate levels were found in the crystalloid group. The incidence of neurologic and organ-related adverse events, as well as 30-day mortality was comparable. CONCLUSION: The use of crystalloid priming is safe in coronary artery bypass grafting surgery in adults. However, there might be a greater need for crystalloid fluids during surgery.


Subject(s)
Albumins/administration & dosage , Cardioplegic Solutions/administration & dosage , Coronary Artery Bypass , Extracorporeal Circulation/instrumentation , Heart-Lung Machine , Potassium Compounds/administration & dosage , Aged , Albumins/adverse effects , Cardioplegic Solutions/adverse effects , Coronary Artery Bypass/adverse effects , Coronary Artery Bypass/mortality , Extracorporeal Circulation/adverse effects , Extracorporeal Circulation/mortality , Female , Germany/epidemiology , Glucose/administration & dosage , Glucose/adverse effects , Heart-Lung Machine/adverse effects , Humans , Incidence , Male , Mannitol/administration & dosage , Mannitol/adverse effects , Potassium Chloride/administration & dosage , Potassium Chloride/adverse effects , Potassium Compounds/adverse effects , Procaine/administration & dosage , Procaine/adverse effects , Retrospective Studies , Risk Factors , Systemic Inflammatory Response Syndrome/epidemiology , Time Factors , Treatment Outcome
20.
Ann Thorac Cardiovasc Surg ; 25(1): 10-17, 2019 Feb 20.
Article in English | MEDLINE | ID: mdl-30158392

ABSTRACT

PURPOSE: The purpose of this study was to evaluate the effect of different cardioplegic solutions on endothelial integrity and oxidative stress in cardiovascular surgery. METHODS: In this randomized prospective study, after ethics approval and informed consent, 60 surgical patients were included. Patients undergoing coronary bypass surgery were randomized into two groups as warm blood cardioplegia (n = 30) and cold crystalloid cardioplegia (n = 30) following the cross-clamping. Measurements were performed at three time points: before induction of anesthesia (T1), at admission to intensive care unit (ICU) (T2) and at the 24th postoperative hour (T3). Besides biochemical routine hemodynamic monitoring, patients were assessed for the sialic acid (SA), ischemic-modified albumin (IMA), advanced oxide protein products (AOPPs), total thiol (SH), and free hemoglobin (fHb) level. RESULTS: Neither crystalloid nor blood cardioplegia led to significant changes in the AOPPs, T-SH, and SA level (p >0.05). Crystalloid cardioplegia, however, increased IMA level compared to both baseline (p <0.01) and blood cardioplegia group (p <0.05). fHb levels were transiently increased in both groups at the second-time point (p <0.001). fHb level was lower in the crystalloid group compared to that in the other group (p <0.05) at T2. CONCLUSION: Cardioplegia type creates similar effects on glycocalyx integrity. However, myocardial protection could be provided with warm blood cardioplegia.


Subject(s)
Cardioplegic Solutions/administration & dosage , Coronary Artery Bypass , Endothelial Cells/drug effects , Glycocalyx/drug effects , Heart Arrest, Induced/methods , Oxidative Stress/drug effects , Potassium Compounds/administration & dosage , Advanced Oxidation Protein Products/blood , Aged , Biomarkers/blood , Cardioplegic Solutions/adverse effects , Cold Temperature , Coronary Artery Bypass/adverse effects , Creatine Kinase, MB Form/blood , Endothelial Cells/metabolism , Endothelial Cells/pathology , Female , Glycocalyx/metabolism , Glycocalyx/pathology , Heart Arrest, Induced/adverse effects , Hemoglobins/metabolism , Humans , Male , Middle Aged , N-Acetylneuraminic Acid/blood , Potassium Compounds/adverse effects , Prospective Studies , Serum Albumin, Human , Sulfhydryl Compounds/blood , Time Factors , Treatment Outcome , Troponin I/blood , Turkey
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