Glutamine Is Cardioprotective in Patients with Ischemic Heart Disease following Cardiopulmonary Bypass
Background: The aim of the present study was to investigate the cardioprotective effects of the perioperative use of N(2)-L-alanyl-L-glutamine (GLN) in patients with ischemic heart disease (IHD) who undergo their operations under cardiopulmonary bypass (CPB).
Methods: This double-blind, placebo-controlled, randomized study included 50 patients who underwent cardiac surgery with CPB. Exclusion criteria were a left ventricular ejection fraction <50%, diabetes mellitus, <3 months since the onset of myocardial infarction, and emergency surgery. Patients in the study group (n = 25) received 0.4 g/kg GLN (Dipeptiven, 20% solution) per day. Patients in the control group (n = 25) were administered a placebo (0.9% NaCl). The primary end point was the dynamics of troponin I at the following stages: (1) prior to anesthesia, (2) 30 minutes after CPB, (3) 6 hours after CPB, (4) 24 hours after surgery, and (5) 48 hours after surgery. Secondary end points included measurements of hemodynamics with a Swan-Ganz catheter.
Results: On the first postoperative day after the surgery, the median troponin I level was significantly lower in the study group than in the placebo group: 1.280 ng/mL (interquartile range [IQR], 0.840-2.230 ng/mL) versus 2.410 ng/mL (IQR, 1.060-6.600 ng/mL) (P = .035). At 4 hours after cardiopulmonary bypass (CPB), the median cardiac index was higher in the patients in the study group: 2.58 L/min per m2 (IQR, 2.34-2.91 L/min per m2) versus 2.03 L/min per m2 (IQR, 1.76-2.32 L/min per m2) (P = .002). The median stroke index also was higher in the patients who received GLN: 32.8 mL/m2 (IQR, 27.8-36.0 mL/m2) versus 26.1 mL/m2 (IQR, 22.6-31.8 mL/m2) (P = .023). The median systemic vascular resistance index was significantly lower in the study group than in the placebo group: 1942 dyn·s/cm5 per m2 (IQR, 1828-2209 dyn·s/cm5 per m2) versus 2456 dyn·s/cm5 per m2 (IQR, 2400-3265 dyn·s/cm5 per m2) (P = .001).
Conclusion: Perioperative administration of GLN during the first 24 hours has cardioprotective effects in IHD patients following CPB. This technique enhances the troponin concentration at 24 hours after surgery and is associated with improved myocardial function.
Engel JM, Mühling J, Kwapisz M, Heidt M. 2009. Glutamine administration in patients undergoing cardiac surgery and the influence on blood glutathione levels. Acta Anaesthesiol Scand 53:1317-23.nHayashi Y, Sawa Y, Fukuyama N, Nakazawa H, Matsuda H. 2002. Preoperative glutamine administration induces heat-shock protein 70 expression and attenuates cardiopulmonary bypass-induced inflammatory response by regulating nitric oxide synthase activity. Circulation 106:2601-7.nKhogali SE, Harper AA, Lyall JA, Rennie MJ. 1998. Effects of l-glutamine on post-ischaemic cardiac function: protection and rescue. J Mol Cell Cardiol 30:819-27.nKhogali SE, Pringle SD, Weryk BV, Rennie MJ. 2002. Is glutamine beneficial in ischemic heart disease? Nutrition 18:123-6.nLiu J, Marchase RB, Chatham JC. 2007. Glutamine-induced protection of isolated rat heart from ischemia/reperfusion injury is mediated via the hexosamine biosynthesis pathway and increased protein O-GlcNAc levels. J Mol Cell Cardiol 42:177-85.nLurati Buse GA, Koller MT, Grapow M, Bolliger D, Seeberger M, Filipovic M. 2010. The prognostic value of troponin release after adult cardiac surgery—a metaanalysis. Eur J Cardiothorac Surg 37:399-406.nMcGuinness J, Neilan TG, Cummins R, Sharkasi A, Bouchier-Hayes D, Redmond JM. 2009. Intravenous glutamine enhances COX-2 activity giving cardioprotection. J Surg Res 152:140-7.nMorrison AL, Dinges M, Singleton KD, Odoms K, Wong HR, Wischmeyer PE. 2006. Glutamine's protection against cellular injury is dependent on heat shock factor-1. Am J Physiol Cell Physiol 290:C1625-32.nMurphy E. 2004. Primary and secondary signaling pathways in early preconditioning that converge on the mitochondria to produce cardioprotection. Circ Res 94:7-16.nMurphy GJ, Angelini GD. 2004. Side effects of cardiopulmonary bypass: What is the reality? J Card Surg 19:481-8.nOudemans-van Straaten HM, Bosman RJ, Treskes M, van der Spoel HJ, Zandstra DF. 2001. Plasma glutamine depletion and patient outcome in acute ICU admissions. Intensive Care Med 27:84-90.nParry-Billings M, Baigrie RJ, Lamont PM, Morris PJ, Newsholme EA. 1992. Effects of major and minor surgery on plasma glutamine and cytokine levels. Arch Surg 127:1237-40.nRoth E, Funovics J, Muhlbacher F, et al. 1982. Metabolic disorders in severe abdominal sepsis: glutamine deficiency in skeletal muscle. Clin Nutr 1:25-41.nRoth E, Oehler R, Manhart N, et al. 2002. Regulative potential of glutamine— relation to glutathione metabolism. Nutrition 18:217-21.nRoth E. 2008. Nonnutritive effects of glutamine. J Nutr 138:2025S-31S.nSuleiman MS, Moffatt AC, Dihmis WC, et al. 1997. Effect of ischaemia and reperfusion on the intracellular concentration of taurine and glutamine in the hearts of patients undergoing coronary artery surgery. Biochim Biophys Acta 1324:223-31.nTakeda S, Nakanishi K, Ikezaki H, et al. 2002. Cardiac marker responses to coronary artery bypass graft surgery with cardiopulmonary bypass and aortic cross-clamping. J Cardiothorac Vasc Anesth 16:421-5.nVosseller K, Sakabe K, Wells L, Hart GW. 2002. Diverse regulation of protein function by O-GlcNAc: a nuclear and cytoplasmic carbohydrate posttranslational modification. Curr Opin Chem Biol 6:851-7.nWischmeyer PE, Van den Hoek TL, Li C, et al. 2003. Glutamine preserves cardiomyocyte viability and enhances recovery of contractile function after ischemia-reperfusion injury. J Parenter Enteral Nutr 27:116-22.nZar JH. 2010. Biostatistical analysis. Upper Saddle River, NJ: Pearson Prentice-Hall. 960 p.n
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).