The Effects of Amino Acids Enriched Del Nido Cardioplegia on Myocardial Leucocyte Accumulation and Ventricular Functions in Patients Undergoing Coronary Artery Bypass Grafting Surgery
Keywords:Myocardial impairement, leucocytes, del Nido cardioplegia, glutamate, aspartate, reperfusion injury, coronary artery by-pass grafting surgery
Background: One of the main sources of ischemia/reperfusion injury (IRI) and release of free oxygen radicals (FORs) during extracorporeal circulation (ECC) during cardiac surgery is neutrophils. In this study, we investigated the potential effects of our modification of del Nido cardioplegia (mDNC) (amino acids enriched del Nido cardioplegia) on myocardial polymorphonuclear leucocyte (PMNL) accumulation. We also compared the effects of our mDND and classical del Nido cardiplegia (cDNC) on ventricular contractile functions in coronary artery bypass grafting (CABG) surgery.
Patients and methods: Our study included 100 isolated CABG patients with similar characteristics, including age, gender, preoperative medications, diabetes, hypertension, and left ventricular ejection fraction (LVEF). The patients were divided into two groups. Amino acids supplemented del Nido cardioplegia (L-aspartate and L-glutamate at a dose of 13 milimol/L) in 50 patients (study group, G1). In the remaining 50 patients, we used a classical del Nido cardioplegic solution (cDNC) (control group, G2). Myocardial Tru-Cut biopsy from the right ventricle was taken before the institution of ECC and after weaning from ECC in all patients. Cardiac troponine-I (cTn-I), tumor necrosis factor-alpha (TNF-Alpha), Pro-Brain Natriuretic Peptide (Pro-BNP), and lactate levels were measured pre- and postoperatively. Invasive monitoring was performed to provide the left ventricular functions in both groups in the operating room and noted by a
Results: Five patients died post-surgery (5%) (two from SG and three from CG (P = .67), due to low cardiac output syndrome or multiorgan failure. At the postoperative period, cardiac output (CO) and stroke volume index (SVI) was higher in mDNC (mean ± SDS; 32.1 ± 7 versus 22.2 ± 6.9 mL/min/m² (P < .001). CI was significantly higher in mDNC after surgery (3.10 ± 0.76 versus 2.40 ± 0.30L/min/m²
(P = .002). Ten patients (20%) in mDNC and 16 patients (32%) in cDNC required inotropic support (P < .001). The postoperative inotropic requirement was less in mDNC (6.1 ± 1.8 mg/kg versus 9.2 ± 1.9 mg/kg, P < .004). Blood gas analyses from the coronary sinus showed that myocardial acidosis was more severe in the control group [pH (0.10 ± 0.09 versus 0.054 ± 0.001; P = .34)]. Blood lactate levels were significantly high in the control group (1.01 ± 0.007 mmol/L versus 1.92 ± 0.35 mmol/L) (P = .22). No difference was found when compared with cardioplegia volume in the mDNC and cDNC groups (mDNC= 990.00 ± 385 mL in DNC = 960 ± 240 mL, P = .070). An aortic cross-clamp time in the mDNC and cDNC groups were 88.4 ± 8.9 min, and 93 ± 11 min, (P = .76), but cardiopulmonary bypass time was significantly low in mDNC (mDNC = 98.3 ± 22.5 min, DNC = 126 ± 19.5 min, P = .0020). TNF-Alpha and Pro-BNP levels in patients received mDNC were significantly low (P = .022). Postoperative cardiac enzyme levels (creatine kinase-MB and high sensitive troponin-I) were significantly low in the mDNC group (P = .0034). Myocardial biopsy results showed that myocardial PMNL accumulation was significantly high in the control group (P = .001). The amount of inotropic agent use was significantly high in the control group (P = .003). After weaning from ECC, the left ventricular stroke work index (LVSWI), cardiac index (CI), and heart rate (HR) were significantly high in the study group (P = .032; P = .002; P = .01). Postoperative blood and blood products requirements were significantly low in the mDNC group (P = .002). At pre-discharge echocardiography, the mDNC group demonstrated significantly higher ventricular ejection fraction (37.9 ± 4.3% and 29.7 ± 3.8%, respectively (P = .003).
Conclusion: Our study findings show that glutamate-aspartate supplemented del Nido cardioplegia significantly decrease myocardial PMNL accumulation with reduced release of biochemical markers, including cardiac troponin-I, TNF-alpha, and Pro-Bnp. Our study results demonstrated that amino acids supplementation in del Nido cardioplegia has some advantages in CABG patients, including the decrease of perioperative myocardial infarction and increase significantly the left ventricular functions including ventricular SVI and CI.
Arseni M. 1998. Potential Cardiovascular Applications of Glutamate, Aspartate, and Other. Amino Acids. Clin. Cardiol. 21,620-24.
Barner HB. 1991. Blood cardioplegia: a review and comparison with crystalloid cardioplegia. Ann Thorac Surg. 52:1354-67.
Bittle JA, Shine KI. 1983. Protection of ischemic rabbit myocardium by glutamic acid. Am J Physiol. 245:406-12.
Bolling KS, Halldorsson A, Allen BS, Rahman S, Wang T, Kronon M, Feinberg H. 1997. Prevention of the hypoxic reoxygenation injury with the use of a leukocyte-depleting filter. J Thorac Cardiovasc Surg. 113: 1081-90.
Breda MA, Drinkwater DC, Laks H, Bhuta S, Corna AF, Davtyan HG, Chang P. 1989. Prevention of reperfusion injury in the neonatal heart with leukocyte-depleted blood. J Thorac Cardiovasc Surg. 97: 654 -/65.
Buckberg GD, Beyersdorf F, Allen BS, Robertson JM. 1995. Integrated myocardial management: background and initial application. J Card Surg. 10:68-89.
Byrne JG, ppleyard RF, Lee CC, Couper GS, Scholl FG, Laurence RG, Cohn LH. 1992. Controlled reperfusion of the regionally ischemic myocardium with leukocyte-depleted blood reduces stunning, the no-reflow phenomenon, and infarct size. J Thorac Cardiovasc Surg. 103: 66-/72.
Carrier M, Pellerin M, Perrault LP, Bouchgard D, Page P, Searle N, et al. 2002. Cardioplegic arrest with L-taurin improves myocardial protection: results of a prospective randomized clinical trial. Ann Thorac Surg. 73:837-41.
Chambers DJ, Haire K, Morley N, Fairbanks L, Strumia E, Young CP, et al. 1996. St. Thomas’ Hospital cardioplegia: enhanced protection with exogenous creatine phosphate. Ann Thorac Surg. 61:67-75.
Chocron S, Alwan K, Toubin G, Clement F, Kaili D, Taberlet C, et al. 1996. Crystalloid cardioplegia route of delivery and cardiac troponin release. Ann Thorac Surg. 62:481-5.
Cohen G, Borger MA, Weisel RD, Rao V. 1999. Intraoperative myocardial protection: current trends and future perspective. Ann Thorac Surg. 68:1995-2001.
Datz FL, Seabold SL, Brown ML, et al. 1997. Society of Nuclear Medicine, Procedure guideline for technetium-99m exametazime (HMPAO) labeled leukocyte scintigraphy for suspected infection/inflammation. Journal of Nuclear Medicine. 38; 987-990.
De Vecci E, Paroni R, Pala MG, Di Credica G, Agape V, Gobbi C, Bonini PA, Paolini G, Grossi A. 1997. Role of leukocytes in free radical production during myocardial revascularization. Heart. 77: 449-/55.
Duman U, Dogan OF. 2006. Transient beneficial effects of glutamate-aspartate-enriched cardioplegia on ventricular functions in coronary artery bypass grafting. J Card Surg. 21(5):523-5.
Engler RL, Schmid-Schonbein GW, Pavelec RS. 1983. Leucocyte capillary plugging in myocardial ischemia and reperfusion in the dog. Am J Pathol. 111:98.
Fiore AC, Swartz MT, Nevett R, Vieth PJ, Magrath RA, Sherrick A, Barner HP. 1998. Intermittent Antegrade Tepid Versus Cold Bloob Cardioplegia in Elective Myocardial Revascularization. Ann Thorac Surg. 65:1559–65.
Fukushima N, Shirakura R, Nakata S, Kaneko M, Miyagawa S, Naka Y, Chang JC, Matsumiya G, Nakano S, Matsuda H. 1994. Study of efficacies of leukocyte-depleted terminal blood cardioplegia in 24-hour preserved hearts. Ann Thorac Surg. 58: 1651-56.
Habazetl H, Martinek V, Vollmar B. 1997. Enhancement of the leukocyte-endothelial cell interaction in collecting venules of skeletal muscle by protamine. J Thorac Cardiovasc Surg. 113:784-91.
Hayashi Y, Sawa Y, Nishimura M, Ichikawa H, Kagisaki K, Ohtake S, Matsuda H. 2000. Clinical evaluation of leukocyte-depleted blood cardioplegia for pediatric open heart operation. Ann Thorac Surg. 69: 1914 -/19.
Hynninen M, Borger MA, Rao V, Weisel RD, Christakis GT, Carroll Cheng DC. 2001. The effect of insulin cardioplegia on atrial fibrillation after high risk coronary bypass surgery: a double-blinded, randomized controlled trial. Anesth Analg. 92:810-6.
Ichihara T, Yasuura K, Maseki T, Matsuura a, Miyahara K, Ito T, Kato S, Mizuno S, Tamaki S, Seki A. 1994. The effects of using a leukocyte removal filter during cold blood cardioplegia. Surg Today. 24:966-72.
Kronon MT, Allen BS, Rahman S, Wang T, Tayyab NA, Bolling KS, Ilbawi MN. 2000. Reducing postischemic reperfusion damage in neonates using a terminal warm substrate-enriched blood cardioplegic reperfusate. Ann Thorac Surg. 70:765-70.
Lewis M, Littlejohns B, Lin H, Angelini GD, Suleiman MS. 2014. Cardiac taurine and principal amino acids in right and left ventricles of patients with either aortic valve stenosis or coronary artery disease: the importance of diabetes and gender. SpringerPlus. 3:523.
Mallidi HR, Sever J, Tamariz M, Singh S, Hanayama N, Christakis GT, et al. 2003. The short-term and long-term effects of warm or tepid cardioplegia. J Thorac Cardiovasc Surg. 125:711-20.
Martin J, Benk C. Multimedia Manuel of Cardiothoracic Surgery. Blood Cardioplegia.
Martin J, Krause M, Benk C, et al. 2003. Blood Cardioplegia filtration Perfusion. 18:75-80.
Mehta JL, Nichols WW, Mehta P. 1983. Neutropils as potential participants in acute myocardial ischemic myocardial injury Am Heart J. 106:8-13.
Mizuno A, Baretti R, Buckberg GD. 1997. Endothelial stunning and myocyte recovery after reperfusion of jeopardized muscle. A role of L-Arginine blood cardioplegia. J Thorac Cardiopvasc Surg. 113:379-89.
Mullane K, Kraemer R, Smith B. 1985. Myeloperoxidase activity as a quantitative assessment of neutrophil infiltration into ischemic myocardium. J Pharmacol Methods.14:157-67.
Mullane KM, Read N, Salmon JA. 1984. Role of lucocytes in acute myocardial infarction in anesthetized dogs: Relationship to myocardial salvage by anti-inflammatory drugs J Pharmacol Exp Ther. 228:510-22.
Palatianos GM, Balentine G, Papadakis EG, Triantafillou CD, Vassili MI, Lidoriki A, Dinopoulos A, Astras GM. 2004. Neutrophil depletion reduces myocardial reperfusion morbidity Ann. Thorac. Surg. 77(3): 956-61.
Pisarenko OI. 1996. Mechanisms of myocardial protection by amino acids: facts and hypotheses. Clin Experimen Pharma & Physio. 23:627-33.
Ren G, Dewald O, Frangogiannis NG. 2003. Inflammatory mechanisms in myocardial infarction. Curr Drug Targets Inflamm Allergy 2: 242–256.
Roth M, Kraus B, Scheffold T, Reuthebuch O, Klo¨vekorn WP, Bauer EP. 2000. The effect of leukocyte-depleted blood cardioplegia in patients with severe left ventricular dysfunction: a randomized, double-blind study. J Thorac Cardiovasc Surg. 120: 642-50.
Rowe G, Manson N, Caplan M. 1983. Hydrogen peroxide and hydroxyl radical mediation of inactivated leucocyte depression of cardiac sarcoplasmic reticulum: Participation of the cyclooxigenase pathway. Circ Res. 53:584-91.
Sato H, Zhao ZQ, Jordan J. 1997. Basal nitric oxyde expresses endogenous cardio protection during reperfusion by inhibition of neutrophil mediated damage after surgical revascularization. J Thorac Cardiovasc Surg. 113:379-89.
Sawa Y, Matsuda H, Shimzaki Y, Kaneko M, Nishimura M, Amemiya A, Sakai K, Nakano S. 1994. Evaluation of leukocyte-depleted terminal blood cardioplegic solution in patients undergoing elective and emergency coronary artery bypass grafting. J Thorac Cardiovasc Surg. 108:1125-31.
Suzuki I, Ogoshi N, Chiba M, Komatsu T, Moizumi Y. 1998. Clinical evaluation of a leukocyte-depleting blood cardioplegia filter (BC1B) for elective open-heart surgery. Perfusion. 13: 205-10.
Tomoeda H. 1999. Effects of leukocyte-depleted warm blood cardioplegia on cardiac and endothelial function. Kurume Med J. 46: 31-38.
Uyar I, Mansuroğlu D, Kirali K, Erentuğ V, Bozbuğa NU, Uysal G, Yakut C. 2005. Aspartate and glutamate-enriched cardioplegia in left ventricular dysfunction. J Card Surg. 20(4):337-44.
Vinten-Johansen J, Yellon DM, Opie LH. 2005. Postconditioning: a simple, clinically applicable procedure to improve revascularization in acute myocardial infarction. Circulation 112: 2085–2088.
Wilson I, Gardner TJ, DiNatalle CM. 1993. Temporary leucocyte depletion reduces ventricular disfunction during prolonged postischemic reperfusion. J Thorac Cardiovasc Surg. 106:805-810.
Yazicioglu Y, Erdogan S. 2004. SPSS Uygulamalı Bilimsel Arastirma Yöntemleri. Detay Yayinlari, Detay Yayincilik, ISBN: 975-8326-98-8. Page 324.
How to Cite
Author Disclosure & Copyright Transfer Agreement
In order to publish the original work of another person(s), The Heart Surgery Forum® must receive an acknowledgment of the Author Agreement and Copyright Transfer Statement transferring to Forum Multimedia Publishing, L.L.C., a subsidiary of Carden Jennings Publishing Co., Ltd. the exclusive rights to print and distribute the author(s) work in all media forms. Failure to check Copyright Transfer agreement box below will delay publication of the manuscript.
A current form follows:
The author(s) hereby transfer(s), assign(s), or otherwise convey(s) all copyright ownership of the manuscript submitted to Forum Multimedia Publishing, LLC (Publisher). The copyright transfer covers the exclusive rights to reproduce and distribute the article and the material contained therein throughout the world in all languages and in all media of expression now known or later developed, including but not limited to reprints, photographic reproduction, microfilm, electronic data processing (including programming, storage, and transmission to other electronic data record(s), or any other reproductions of similar nature), and translations.
However, Publisher grants back to the author(s) the following:
- The right to make and distribute copies of all or part of this work for use of the author(s) in teaching;
- The right to use, after publication in The Heart Surgery Forum, all or part of the material from this work in a book by the author(s), or in a collection of work by the author(s);
- The royalty-free right to make copies of this work for internal distribution within the institution/company that employs the author(s) subject to the provisions below for a work-made-for-hire;
- The right to use figures and tables from this work, and up to 250 words of text, for any purpose;
- The right to make oral presentations of material from this work.
Publisher reserves the right to grant or refuse permission to third parties to republish all or part of the article or translations thereof. To republish, such third parties must obtain written permission from the Publisher. (This is in accordance with the Copyright Statute, United States Code, Title 17. Exception: If all authors were bona fide officers or employees of the U.S. Government at the time the paper was prepared, the work is a “work of the US Government” (prepared by an officer or employee of the US Government as part of official duties), and therefore is not subject to US copyright; such exception should be indicated on signature lines. If this work was prepared under US Government contract or grant, the US Government may reproduce, royalty-free, all or portions of this work and may authorize others to do so, for official US Government purposes only, if the US Government contract or grant so requires.
I have participated in the conception and design of this work and in the writing of the manuscript and take public responsibility for it. Neither this manuscript nor one with substantially similar content under my authorship has been published, has been submitted for publication elsewhere, or will be submitted for publication elsewhere while under consideration by The Heart Surgery Forum, except as described in an attachment. I have reviewed this manuscript (original version) and approve its submission. If I am listed above as corresponding author, I will provide all authors with information regarding this manuscript and will obtain their approval before submitting any revision. I attest to the validity, accuracy, and legitimacy of the content of the manuscript and understand that Publisher assumes no responsibility for the validity, accuracy, and legitimacy of its content. I warrant that this manuscript is original with me and that I have full power to make this Agreement. I warrant that it contains no matter that is libelous or otherwise unlawful or that invades individual privacy or infringes any copyright or other proprietary right. I agree to indemnify and hold Publisher harmless of and from any claim made against Publisher that relates to or arises out of the publication of the manuscript and agree that this indemnification shall include payment of all costs and expenses relating to the defense of any such claim, including all reasonable attorney’s fees.
I warrant that I have no financial interest in the drugs, devices, or procedures described in the manuscript (except as disclosed in the attached statement).
I state that the institutional Human Subjects Committee and/or the Ethics Committee approved the clinical protocol reported in this manuscript for the use of experimental techniques, drugs, or devices in human subjects and appropriate informed consent documents were utilized.
Furthermore, I state that any and all animals used for experimental purposes received humane care in USDA registered facilities in compliance with the “Principles of Laboratory Animal Care” formulated by the National Society for Medical Research and the “Guide for the Care and Use of Laboratory Animals” prepared by the Institute of Laboratory Animal Resources and published by the National Institutes of Health (NIH Publication No. 85-23, revised 1985).