Effects of glycine supplementation on myocardial damage and cardiac function after severe burn

doi:10.1016/j.burns.2012.09.006

Burns

Volume 39, Issue 4, June 2013, Pages 729-735

https://doi.org/10.1016/j.burns.2012.09.006 Get rights and content

Abstract

Background

Glycine has been shown to participate in protection from hypoxia/reoxygenation injury. However, the cardioprotective effect of glycine after burn remains unclear. This study aimed to explore the protective effect of glycine on myocardial damage in severely burned rats.

Methods

Seventy-two Wistar rats were randomly divided into three groups: normal controls (C), burned controls (B), and glycine-treated (G). Groups B and G were given a 30% total body surface area full-thickness burn. Group G was administered 1.5 g/(kg d) glycine and group B was given the same dose of alanine via intragastric administration for 3 d. Serum creatine kinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST), and blood lactate, as well as myocardial ATP and glutathione (GSH) content, were measured. Cardiac contractile function and histopathological changes were analyzed at 12, 24, 48, and 72 hours.

Results

Serum CK, LDH, AST, and blood lactate increased, while myocardial ATP and GSH content decreased in both burned groups. Compared with group B, the levels of CK, LDH, and AST significantly decreased, whereas blood lactate as well as myocardial ATP and GSH content increased in group G. Moreover, cardiac contractile function inhibition and myocardial histopathological damage in group G significantly decreased compared with group B.

Conclusion

Myocardial histological structure and function were damaged significantly after burn. Glycine is beneficial to myocardial preservation by improving cardiomyocyte energy metabolism and increasing ATP and GSH abundance.

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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In a separate study, oral treatment of elderly subjects with both NAC (0.81 mmol) and glycine (1.33 mmol) for 14 days restored low baseline levels of cysteine, glycine, and GSH/GSSH ratio in the red blood cells to that of young untreated subjects (Sekhar et al., 2011a,b). In rodents, intragastric administration of glycine (1.5 g/kg/day for 3 days) was sufficient to increase myocardial GSH content following a severe burn (Zhang et al., 2013). So far, most research using glycine treatments have been performed in patient or elderly populations and while a high-dose regimen of oral glycine treatment (10 g/day for 14 days) was shown to increase glycine levels in the brain in healthy men (Kaufman et al., 2009), it is not yet known whether glycine supplementation will increase brain GSH levels in a healthy population.
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¹: These authors contributed equally to this work.

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Effects of glycine supplementation on myocardial damage and cardiac function after severe burn

Abstract

Background

Methods

Results

Conclusion

Introduction

Section snippets

Drugs and reagents

Experimental animals

Myocardial histology

Glycine administration could improve myocardial energy metabolism after burn

Conflict of interest

Acknowledgments

Burns

Resuscitation

Burns

Leg Med (Tokyo)

Resuscitation

Resuscitation

Surgery

Am J Pathol

Nutrition

J Surg Res

J Mol Cell Cardiol

Nutrition

Am J Clin Nutr

Biochem Biophys Res Commun