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Ann Thorac Surg 2006;81:613-618
© 2006 The Society of Thoracic Surgeons

Original article: Cardiovascular

Cardioprotective Effect of Cold-Blood Cardioplegia Enriched with N-Acetylcysteine During Coronary Artery Bypass Grafting

Ismail Koramaz, MD a , * , Zerrin Pulathan, MD a , Sefer Usta, MD a , S. Caner Karahan, MD b , Ahmet Alver, PhD b , Ersin Yaris, MD, PhD c , Nuri Ihsan Kalyoncu, MD c , Fahri Ozcan, MD a

a Department of Cardiovascular Surgery, School of Medicine, Karadeniz Technical University, Trabzon, Turkey
b Department of Biochemistry, School of Medicine, Karadeniz Technical University, Trabzon, Turkey
c Department of Pharmacology, School of Medicine, Karadeniz Technical University, Trabzon, Turkey

Accepted for publication August 15, 2005.

* Address correspondence to Dr Koramaz, Karadeniz Technical University, School of Medicine, Department of Cardiovascular Surgery, TR-61187 Trabzon, Turkey (Email: ismailkoramaz{at}yahoo.com).


   Abstract
Top
 Abstract
Introduction
 Material and Methods
 Results
 Comment
 Notice From the American...
 Acknowledgments
 References
 
BACKGROUND: Cold-blood cardioplegia is a well-known method in coronary artery bypass graft surgery, and several authors have used various agents in the enrichment of cold-blood cardioplegia to decrease ischemia–reperfusion injury seen during surgery. N-acetylcysteine, which can increase glutathione levels, is one of the agents added to cardioplegic solutions to decrease myocardial injury. This study was planned to assess the efficiency of N-acetylcysteine–enriched cold-blood cardioplegia on early reperfusion injury in patients with ischemic heart disease undergoing coronary artery bypass grafting, using measurements of cardiac troponin I and malondialdehyde release.

METHODS: Thirty patients (11 women and 19 men) with left ventricular ejection fraction greater than 0.40 scheduled for coronary artery bypass grafting were randomly divided into two groups. We used cold-blood cardioplegia enriched with N-acetylcysteine (50 mg per kilogram of body weight) in the first group and cold-blood cardioplegia alone in the second group. Hemodynamic variables and clinical properties of the patients were preoperatively and postoperatively evaluated. Enzyme releases were measured in the early hours after the operation.

RESULTS: In the N-acetylcysteine–enriched group cardiac troponin I levels were lower than in the N-acetylcysteine–free group, and this difference was statistically significant. Cardiac troponin I levels increased in both groups in the 6th and 12th hours postoperatively, but there was a statistically significant difference between the two groups. Malondialdehyde levels were significantly higher in the N-acetylcysteine–free group after the 6th, 12th, 24th, and 48th hours postoperatively when compared with the N-acetylcysteine–enriched group.

CONCLUSIONS: N-acetylcysteine–supplemented cold-blood cardioplegia minimizes myocardial injury in the early hours after and during the cardiac surgery.


   Introduction
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 Abstract
 Introduction
Material and Methods
 Results
 Comment
 Notice From the American...
 Acknowledgments
 References
 
Myocardial ischemia commonly complicates vascular surgery. This ischemia and then reperfusion may affect both cardiac myocytes and coronary endothelial cells and appears to be a major factor contributing to perioperative myocardial damage. Generation of oxygen free radicals during the early phase of reperfusion has been recognized as the source of these injuries [1, 2]. Excessive generation of oxygen free radicals causes macromolecular damage, lipid peroxidation, and tissue damage [3]. The alterations in membrane permeability, configuration, and cellular proteins caused by oxygen free radicals have been suggested as the main cause for ischemia–reperfusion injury [1].

Various antioxidant agents and cardioplegic arrest techniques have been used to prevent myocardial injury and oxidative stress during coronary artery bypass grafting (CABG) [4–8]. However, these treatment modalities are not standardized for routine usage, and there is still a need to identify an effective and convenient agent to protect myocardial tissue against damage of ischemia–reperfusion injury during cardiac surgery.

N-acetylcysteine (NAC) is a thiol-containing low-molecular-weight compound that has been used as an antioxidant to prevent depletion of intracellular glutathione (GSH) stores in several disease processes [9, 10]. Glutathione and glutathione disulfide are important thiols, which provide defense against oxidative stress by scavenging free radicals or causing the reduction of hydrogen peroxide. It has been reported that the amount of myocardial injury is inversely dependent on both the myocardial GSH content and the GSH to glutathione disulfide ratio within the ischemic tissues reduced during myocardial ischemia and reperfusion [11, 12].

The aim of the present study is to investigate the efficiency of NAC-enriched cold-blood cardioplegia on early reperfusion injury in patients with ischemic heart disease undergoing CABG, compared with NAC-free cold-blood cardioplegia.


   Material and Methods
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 Abstract
 Introduction
 Material and Methods
Results
 Comment
 Notice From the American...
 Acknowledgments
 References
 
Patients
This study was approved (approval no. 2003/12) by the local ethics committee of the School of Medicine of Karadeniz Technical University, and informed consents were obtained from all patients. Patients with poor ventricular function (ejection fraction < 0.30) or diabetes mellitus and those requiring emergency surgery were not included in the study. Any patients exhibiting remarkably abnormal pulmonary, endocrine, metabolic, or neurologic disease were also excluded. Thirty patients with coronary artery disease who had no exclusion criteria and who would undergo elective, isolated, primary CABG operation were selected from the waiting list and randomly assigned by a random number generator either to NAC-enriched or NAC-free groups, each including 15 patients (Table 1). The first (NAC-enriched) group (n = 15) received NAC (Asist, Husnu Arsan Co, Istanbul, Turkey) at a dose of 50 mg per kilogram of body weight within the cold-blood cardioplegia, and the second (NAC-free) group (n = 15) received cold-blood cardioplegia alone. Cold blood was driven from the pump and, after the injection and mixing of NAC and potassium chloride in the plastic, sterile apyrogenic bag in which the blood was collected, this cardioplegic solution was given to patients by means of the aortic root.


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  		Table 1. Demographic, Preoperative, Surgical, and Postoperative Data a
 
Operative Procedures
Anesthetic management was uniform in all patients. Midazolam was used for premedication, and the combination of fentanyl, midazolam, and pancuronium was used for the induction of anesthesia. After intubation, mechanical ventilation with oxygen and nitrogen was started. Anesthesia was maintained with midazolam, vecuronium, and inhaled sevoflurane. Patients were operated on by the same surgical team. Coronary artery bypass grafting was performed with moderate hypothermia. After the aorta was cross-clamped and 1,000 mL of high-potassium (enriched with NAC) cold (24° to 26°C) blood cardioplegic solution was perfused in an antegrade fashion, myocardial revascularization was performed during cardioplegic arrest at 28°C to 30°C. The cardioplegic solution was composed of whole blood with a hemoglobin level of 8 g/dL and 25 mEq/L potassium chloride. After that, 500 mL of low-potassium cold-blood cardioplegia (10 mEq/L potassium chloride) was infused through the aortic root every 20 minutes. N-acetylcysteine was added only into the cold-blood cardioplegic solution with high potassium.

The distal and proximal anastomoses were constructed during a single period of total aortic occlusion. Left internal thoracic artery to left anterior descending artery was used in all cases. Before the discontinuation of aortic clamping each patient received a 500-mL hot shot through the aortic root. After the completion of CABG, patients were transferred to the intensive care unit. Postoperative care was standardized for all patients, and extubation was done as early as possible. When there was a low cardiac output state, dopamine was used as the first-choice inotropic agent. In the cases of a new onset of atrial fibrillation, amiodarone was used as the first-choice antiarrhythmic agent.

Serial venous blood samples were drawn just before cardiopulmonary bypass, during aortic clamping, and after release of the clamp. Venous blood samples were also obtained at aortic cross-clamp time and at the 6th, 12th, 24th, and 48th postoperative hours. All of the venous blood samples were centrifuged and frozen at –80°C for cardiac troponin I (CTnI) and malondialdehyde (MDA) measurements.

Hemodynamic Measurements
Standard radial and central venous catheters were preoperatively inserted. Hemodynamic data including heart rate and blood pressure was recorded every 1 hour for the first 3 postoperative days. Central venous pressure was measured every 2 hours during the first postoperative day. Cardiac index, cardiac output, and ejection fraction were preoperatively assessed just before the operation and 5 days after surgery using two-dimensional echocardiography (Table 2). A cardiologist, blinded to the patients' clinical history and biochemical values, performed all echocardiographic studies.


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  		Table 2. Preoperative and Postoperative Echocardiographic Data a
 
Measurement of Cardiac Troponin I
All measurements were made at all time points, and there were no missing data. Cardiac troponin I concentration was assayed with a solid-phase two-side chemiluminescence enzyme immunometric assay (BioDPS, Los Angeles, CA) using an Immulite analyzer (BioDPS) in the same samples. The upper reference limits for the normal ranges were set at CTnI 1.0 ng/mL.

Measurement of Malondialdehyde
After sera were obtained from patients, they were kept at –80°C until analysis. Lipid peroxidation in samples was determined as MDA concentration by the method of Yagi [13]. Briefly, 0.3 mL of serum was mixed with 2.4 mL of 1/12 N H2SO4 and 0.3 mL of 10% phosphotungstic acid. After being allowed to stand at room temperature for 5 minutes, the mixture is centrifuged at 1,600 g for 10 minutes. The supernatant was discarded, and the sediment was suspended in 4 mL of distilled water. After that, 1 mL of 0.67% thiobarbituric acid was added, and the mixture was heated in boiling water for 60 minutes. The formed color was extracted into n-butanol. The mixture was centrifuged at 1,600 g for 10 minutes. The absorbance of the organic layer was read at 532 nm. Tetramethoxypropane was used as a standard, and MDA levels were calculated as nanomoles per milliliter.

Statistical Analysis
Data normality was assessed by the Kolmogorov-Smirnov test. In each group, comparisons among measures (before cardiopulmonary bypass, during aortic clamping time, and at 6, 12, 24, and 48 hours postoperatively) of CTnI and MDA were made with Friedman variance of analysis (with Bonferroni correction and Wilcoxon as a post hoc test) for not normally distributed variables. Comparisons between groups were made with Mann-Whitney U test for variables not normally distributed and Student's t test for variables distributed normally. For the comparison of categorical variables, the {chi}2 test was used. Results are cited as mean ± standard deviation, and a p value of less than 0.05 was accepted as significantly different.


   Results
Top
 Abstract
 Introduction
 Material and Methods
 Results
Comment
 Notice From the American...
 Acknowledgments
 References
 
Demographic properties and preoperative and postoperative characteristics of the patient groups were shown in Tables 1 and 2. No patient had perioperative myocardial infarction. There was not any significant difference in the use of inotropic agents and postoperative drainage between patient groups. In our study, all patients in the NAC-enriched group had spontaneous return of sinus rhythm. One of the patients in the NAC-free group died as a result of low cardiac output syndrome 72 hours after the operation. Intraaortic balloon counter pulsation was used only in this patient. Although there is no statistically significant difference in postoperative cardiac index values (p = 0.813) and systolic index volume values (p = 0.773) between NAC-free and NAC-enriched groups, significant differences were observed in ejection fraction, left ventricular end-diastolic length, left ventricular end-systolic length, and left ventricular end-systolic medial wall stress measurements (p = 0.012, p = 0.000, p = 0.000, p = 0.020, respectively) between NAC-free and NAC-enriched groups measured in postoperative period (Table 2). The lengths of stay in the intensive care unit (p = 0.000) and in the hospital (p = 0.000) were shorter in patients treated in the NAC-enriched group (Table 1). The number of patients included for the calculation of data mean was 15 for preoperative and 14 for postoperative measurements.

Cardiac Troponin I Measurement
The preoperative serum concentrations of CTnI were similar in the two groups. Cardiac troponin I increased significantly in both groups as a function of time compared with baseline measurements. At the 6th and 12th postoperative hours, CTnI levels were statistically higher in both groups compared with perioperative levels. In the NAC-enriched group CTnI levels were lower than in the NAC-free group, and this difference was statistically significant (p = 0.018 and p = 0.014, respectively; Fig 1). The measurements from the patient who died were not included, and n is 14 for the NAC-free and 15 for the NAC-enriched groups.


Figure 1
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  		Fig 1. Time courses of cardiac troponin I extraction of both groups. Values are mean ± standard error of the mean, n = 14 (NAC-free), n = 15 (NAC-enriched). *p < 0.05 versus NAC-enriched. (NAC = N-acetylcysteine; Preop = preoperative.)

 
Malondialdehyde Measurement
The preoperative serum concentrations of MDA levels were similar in the two groups. After the surgical intervention, MDA levels significantly increased. Malondialdehyde levels were statistically higher in the NAC-free group after the 6th, 12th, 24th, and 48th (p = 0.000) postoperative hours when compared with the NAC-enriched group (Fig 2). The measurements from the patient who died were not included, and n is 14 for the NAC-free and 15 for the NAC-enriched groups.


Figure 2
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  		Fig 2. Time courses of malondialdehyde (MDA) extraction of both groups. Values are mean ± standard error of the mean, n = 14 (NAC-free), n = 15 (NAC-enriched). *p < 0.05 versus NAC-enriched. (NAC = N-acetylcysteine; Preop = preoperative.)

 

   Comment
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
Notice From the American...
 Acknowledgments
 References
 
The heart needs oxygen but it is also susceptible to oxidative stress. Ischemia causes alterations in the defense mechanisms against oxygen free radicals and increases production of oxygen free radicals. It has been proved that oxidative stress occurs after reperfusion in cardiopulmonary bypass, and it is related to transient left ventricular dysfunction or stunning [14]. Ischemia–reperfusion injury after CABG may cause reperfusion arrhythmias, microvascular damage, and myocardial stunning and cell death. Although numerous experimental investigations have demonstrated that scavenging radicals attenuates myocardial ischemia–reperfusion injury, only a few clinical studies have addressed the ability to ameliorate myocardial injury associated with cardiopulmonary bypass and cardioplegic arrest. At this point, the cardioprotective effects of NAC in clinical and experimental studies should be documented.

N-acetylcysteine is a pharmacologic agent containing thiol groups that are transferable to intracellular sites [15], and it is used as an antioxidant to replete intracellular GSH stores [16] in several disease processes [9, 10, 12]. N-acetylcysteine, an oxidant scavenger, promotes glutathione in its reduced form (GSH), which is depleted during ischemia. Glutathione plays an important scavenging role in cellular defense mechanisms against oxygen free radicals, and also acts extracellularly, either directly or by means of glutathione peroxidase catalysis [17–21].

It was shown that when subjected to conditions of ischemia–reperfusion, myocardium pretreated with NAC had increased GSH concentrations [15–17]. Recent studies have shown the cardioprotective effects of NAC in the cardioplegia or the priming volume used perioperatively during cardiopulmonary bypass [17–22]. The dose of NAC (50 to 100 mg/kg) differs among the investigations [16–22], and the routes of administration of NAC during the perioperative procedures were not the same [16–22]. The dose selected in this study is not the highest dose used in the literature, and the cardioplegic solution, which is one of the common methods for on-pump techniques, was used for the route of administration of NAC.

Cardiac troponin I is used for the diagnosis of small perioperative necrotic myocardial areas, and it is a specific marker of myocardial injury. Cardiac troponin I measurements can detect small differences in myocardial tissue damage because it is highly sensitive and specific for myocardial tissue [23–25]. As mentioned before, CTnI levels were high in our patient groups because of ischemia caused by the surgical intervention. However, this increase was significantly reduced by NAC (Fig 1). This finding suggests a cardiac protective role for NAC exists in ischemic conditions. There are no available clinical data in the literature showing the successful effect of NAC in ischemia induced by CABG on the basis of CTnI measurements. However, Palmer and associates [26] reported that NAC reduced the amount of some oxygen free radicals, which may be protective for CTnI of rabbit myocytes in early phases of ischemia (but not the reperfusion period) by means of densitometric analysis without an improvement in hemodynamic variables. That these results are inconsistent with ours can be attributed to the divergent roles of oxygen free radicals during ischemia and reperfusion.

Malondialdehyde, one oxidative product of lipids (lipid peroxidation), is an important marker of oxidative stress and ischemia–reperfusion injury that is not specific to myocardial oxidative stress. In our patients MDA levels were also higher after surgical operation, and this increase was also significantly reduced by NAC (Fig 2). Our findings suggest a protective role of NAC against oxidative stress that is not specific to myocardial ischemia. When the positive effects of NAC on CTnI and MDA levels are evaluated together, we can say that the effect of NAC is not specific for myocardial tissue and can be widened to a protection against oxidative stress in general.

Although NAC did not worsen the clinical features of our patients, it improved some clinical measurements such as ejection fraction, left ventricular end-diastolic length, left ventricular end-systolic length, and left ventricular end-systolic medial wall stress. These improvements can be attributed to the cardiac protective effect of NAC as discussed above. Some authors reported some improvements in clinical properties when NAC is used [14–19], although any positive alterations could not be obtained in the levels of serum markers.

Despite surgical and pharmacologic advances in myocardial preservation during CABG, myocardial ischemia–reperfusion damage remains the most uncontrolled aspect of cardiac operations. We conclude that supplementation of cold-blood cardioplegia with NAC may have a beneficial myocardial protective effect in the early period of CABG. By means of its protecting effect for the GSH stores that can be depleted by surgical ischemia, NAC may minimize the myocardial injury suggested by postoperative high CTnI and MDA levels.


   Notice From the American Board of Thoracic Surgery
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 Material and Methods
 Results
 Comment
 Notice From the American...
Acknowledgments
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The 2006 Part I (written) examination will be held on Monday, December 4, 2006. It is planned that the examination will be given at multiple sites throughout the United States using an electronic format. The closing date for registration is August 1, 2006. Those wishing to be considered for examination must apply online at www.abts.org.

To be admissible to the Part II (oral) examination, a candidate must have successfully completed the Part I (written) examination.

A candidate applying for admission to the certifying examination must fulfill all the requirements of the Board in force at the time the application is received.

Please address all communications to the American Board of Thoracic Surgery, 6333 N St. Clair St, Suite 2320, Chicago, IL 60611; telephone: (312) 202-5900; fax: (312) 202-5960; e-mail: mailto:info{at}abts.org.


   Acknowledgments
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 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Notice From the American...
 Acknowledgments
References
 
The authors wish to thank Gamze Can, MD, for statistical analysis and Emma Duncan for checking the article.


   References
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 Abstract
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 Material and Methods
 Results
 Comment
 Notice From the American...
 Acknowledgments
 References
 

  1. Dhalla NS, Panagia V, Singal PK, Makino N, Dixon IM, Eyolfson DA. Alterations in heart membrane calcium transport during the development of ischemia-reperfusion injury J Mol Cell Cardiol 1988;20(Suppl 2):3-13.[Medline]
  2. Bolli R. Causative role of oxyradicals in myocardial stunning: a proven hypothesis. A brief review of the evidence demonstrating a major role of reactive oxygen species in several forms of postischemic dysfunction Basic Res Cardiol 1998;93:156-162.[Medline]
  3. Yu BP. Cellular defenses against damage from reactive oxygen species Physiol Rev 1994;74:139-162.[Free Full Text]
  4. Woo YJ, Taylor MD, Cohen JE, et al. Ethyl pyruvate preserves cardiac function and attenuates oxidative injury after prolonged myocardial ischemia J Thorac Cardiovasc Surg 2004;127:1262-1269.[Abstract/Free Full Text]
  5. Fadillioglu E, Oztas E, Erdogan H, et al. Protective effects of caffeic acid phenethyl ester on doxorubicin-induced cardiotoxicity in rats J Appl Toxicol 2004;24:47-52.[Medline]
  6. Kiziltepe U, Tunctan B, Eyileten ZB, et al. Efficiency of L-arginine enriched cardioplegia and non-cardioplegic reperfusion in ischemic hearts Int J Cardiol 2004;97:93-100.[Medline]
  7. Pichon H, Chocron S, Alwan K, et al. Crystalloid versus cold blood cardioplegia and cardiac troponin I release Circulation 1997;96:316-320.[Medline]
  8. Yau TM, Weisel RD, Mickle DA, et al. Vitamin E for coronary bypass operations. A prospective, double-blind, randomized trial J Thorac Cardiovasc Surg 1994;108:302-310.[Abstract/Free Full Text]
  9. Bernard GR, Lucht WD, Niedermeyer ME, Snapper JR, Olgetree ML, Brigham KL. Effects of N-acetylcysteine on pulmonary response to endotoxin in the awake sheep and upon in vitro granulocyte function J Clin Invest 1984;73:1772-1784.[Medline]
  10. Rumack BH, Peterson RC, Koch CG, Amara JA. Acetaminophen overdose662 cases with evaluation of oral acetylcysteine treatment. Arch Intern Med 1981;141:380-385.[Abstract/Free Full Text]
  11. Chen W, Gabel S, Steenbergen C, Murphy E. A redox-based mechanism for cardioprotection induced by ischemic preconditioning in perfused rat heart Circ Res 1995;77:424-429.[Abstract/Free Full Text]
  12. Burgunder JM, Varriale A, Lauterburg BH. Effect of N-acetylcysteine on plasma cysteine and glutathione levels following paracetamol administration Eur J Clin Pharmacol 1989;36:127-131.[Medline]
  13. Yagi K. Lipid peroxides and related radicals in clinical medicineIn: Armstrong D, editor. Free radicals in diagnostic medicine. New York: Plenum; 1994. pp. 1-15.
  14. Ferrari R, Agnoletti L, Comini L, et al. Oxidative stress during myocardial ischemia and heart failure Eur Heart J 1998;19(Suppl B):B2-B11.[Medline]
  15. Andrews NP, Prasad A, Quyyumi AA. N-acetylcysteine improves coronary and peripheral vascular function J Am Coll Cardiol 2001;37:117-123.[Abstract/Free Full Text]
  16. Nishikawa Y, Kanki H, Ogawa S. Differential effects of N-acetylcysteine on nitroglycerin- and nicorandil-induced vasodilation in human coronary circulation J Cardiovasc Pharmacol 1998;32:21-28.[Medline]
  17. Sucu N, Cinel I, Unlu A, et al. N-acetylcysteine for preventing pump-induced oxidoinflammatory response during cardiopulmonary bypass Surg Today 2004;34:237-242.[Medline]
  18. Cailleret M, Amadou A, Andrieu-Abadie N, et al. N-acetylcysteine prevents the deleterious effect of tumor necrosis factor-(alpha) on calcium transients and contraction in adult rat cardiomyocytes Circulation 2004;109:406-411.[Abstract/Free Full Text]
  19. Tossios P, Bloch W, Huebner A, et al. N-acetylcysteine prevents reactive oxygen species-mediated myocardial stress in patients undergoing cardiac surgeryresults of a randomized, double-blind, placebo-controlled clinical trial. J Thorac Cardiovasc Surg 2003;126:1513-1520.[Abstract/Free Full Text]
  20. Fischer UM, Tossios P, Huebner A, Geissler HJ, Bloch W, Mehlhorn U. Myocardial apoptosis prevention by radical scavenging in patients undergoing cardiac surgery J Thorac Cardiovasc Surg 2004;128:103-108.[Abstract/Free Full Text]
  21. Ceconi C, Curello S, Cargnoni A, Ferrari R, Albertini A, Visioli O. The role of glutathione status in the protection against ischemic and reperfusion damageeffects of N-acetyl cysteine. J Mol Cell Cardiol 1988;20:5-13.[Medline]
  22. Vento AE, Nemlander A, Aittomaki J, Salo J, Karhunen J, Ramo OJ. N-acetylcysteine as an additive to crystalloid cardioplegia increased oxidative stress capacity in CABG patients Scand Cardiovasc J 2003;37:349-355.[Medline]
  23. Etievent JP, Chocron S, Toubin G, et al. Use of cardiac troponin I as a marker of perioperative myocardial ischemia Ann Thorac Surg 1995;59:1192-1194.[Abstract/Free Full Text]
  24. Adams III JE, Sicard GA, Allen BT, et al. Diagnosis of perioperative myocardial infarction with measurement of cardiac troponin I N Engl J Med 1994;330:670-674.[Abstract/Free Full Text]
  25. Adams JE, Bodor GS, Davila-Roman VG, et al. Cardiac troponin I. A marker with high specificity for cardiac injury Circulation 1993;88:101-106.[Abstract/Free Full Text]
  26. Palmer BS, Klawitter PF, Reiser PJ, Angelos MG. Degradation of rat cardiac troponin I during ischemia independent of reperfusion Am J Physiol Heart Circ Physiol 2004;287:H1269-H1275.[Abstract/Free Full Text]



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