Effects of glycine supplementation on myocardial damage and cardiac function after severe burn
Introduction
Ischemic/hypoxic damage induced by burn stress is a major cause of heart injury after severe burn. Our previous study showed that regional myocardial blood flow and myocardium ATP synthesis decrease significantly in the early stages of severe burn [1], [2]. To date, an effective therapeutic measure for myocardial protection in burn patients has not been found. Fluid resuscitation and cardiotonic drugs are currently the main therapeutic methods after burn [3], [4], [5]. Fluid infusion may increase blood volume and improve hemodynamic parameters. However, low cardiac output and myocardial hypoxia–ischemia are not completely resolved. Excessive fluid infusion may aggravate cardiac preload and increase myocardial damage. Therefore, fluid infusion cannot fundamentally correct cardiac muscle ischaemia and alleviate cardiac muscle damage [6], [7], [8], [9]. Cardiotonic drugs can improve myocardial contractility and partly improve the derangement of blood stream dynamics. However, they cannot fundamentally repair the imbalance in oxygen supply and consumption in cardiac myocytes [10]. Therefore, discovery of therapeutic regimens is necessary for improving energy metabolism, reducing myocardial cell damage, and ameliorating myocardial function.
In recent years, many studies found that glycine protects mammalian cells against ischemic injury and accelerate cellular recovery by preventing cellular membrane leakage, inhibiting cell calcium overload, and improving mitochondrial function [11], [12]. Several studies have proven that the glycine receptor is expressed in cardiomyocytes and participates in cytoprotection from hypoxia/reoxygenation injury [11], [13], [14]. Glycine protects cardiomyocytes against ischemia–reperfusion (IR) injury by inhibiting mitochondrial permeability transition [15]. Therefore, glycine is an important myocardial cytoprotective agent. However, the cytoprotective effect of glycine on cardiocytes after burn is rarely studied. The present study evaluated the therapeutic effect of glycine on rat cardiac damage induced by severe burn and explored the possible mechanisms.
Section snippets
Drugs and reagents
Glycine and ATP were obtained from Sigma Chemical Co. (St. Louis, MO). Blood lactic acid and glutathione (GSH) detection kits were obtained from the Nanjing Jiancheng Bioengineering Institute (Nanjing, China). Alanine injections were purchased from Fujian Haiwang Pharmaceutical Ltd. (Fuzhou, China). All other chemicals and reagents were of analytical grade.
Experimental animals
Seventy-two male adult Wistar rats weighing 200–245 g were offered by the Laboratory Animal Center, Third Military Medical University. The
Myocardial histology
Changes in the pathomorphological features of the myocardium appeared after burn. Cardiac interstitial edema, fiber engorgement, transverse striation derangement, cell boundary unsharpness, and cytoplasm destruction were observed at 12 PBH. Inflammatory appearances, such as blood capillary engorgement and erythrocyte exudation, were also observed in the myocardial tissues at 72 PBH. Group G exhibited less structural damage compared with group B. The major pathomorphological changes include
Glycine administration could improve myocardial energy metabolism after burn
The main energy sources of cardiac myocytes are glucose and fatty acids. However, some special amino acids and their metabolites, such as glutamine, glycine, and GSH, can augment ATP synthesis and decrease energy dyssynthesis in pathological state [16], [17], [18], [19]. Studies have shown that glycine can improve energy synthesis by protecting mitochondrial function in cardiac IR injury [20]. The results of the present study indicated an obvious abnormality in energy synthesis and reserve in
Conflict of interest
None declared.
Acknowledgments
This work was supported by the National Natural Science Foundation of China (Grant No. 30670773), National Key New Drug Creation Project (2009ZX09103-647), and the Clinical Research Foundation of TMMU (Grant No. 2009XLC10).
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These authors contributed equally to this work.