Single dose of glutamine enhances myocardial tissue metabolism, glutathione content, and improves myocardial function after ischemia-reperfusion injury.
BACKGROUND
Myocardial ischemia and reperfusion (I/R) injury causes significant morbidity and mortality. Protection against I/R injury may occur via preservation of tissue metabolism and ATP content, preservation of reduced glutathione, and stimulation of heat shock protein (HSP) synthesis. Supplementation with glutamine (GLN) has been reported to have beneficial effects on all of these protective pathways. Thus, we hypothesized that GLN pretreatment given to the rat in vivo would protect the myocardium against I/R-induced dysfunction.


METHODS
GLN (0.52 g/kg, intraperitoneally, given as alanine-glutamine dipeptide), alanine alone (0.23 g/kg), or a Ringer's lactate solution (control) was administered to Sprague-Dawley rats 18 hours before heart excision, perfusion, exposure to global ischemia (15 minutes) and reperfusion (1 hour). Tissue metabolites were analyzed via magnetic resonance spectroscopy.


RESULTS
In control and alanine-treated animals, I/R injury resulted in cardiac dysfunction, indicated by a decrease in cardiac output. Administration of GLN 18 hours before I/R injury preserved cardiac output after reperfusion. Metabolic analysis of the myocardial tissue revealed that [/R injury led to significant diminution of myocardial tissue glutamate, ATP content, accumulation of myocardial lactate, and a reduction in reduced glutathione content in control animals. GLN significantly reduced the deleterious changes in myocardial metabolism and improved reduced glutathione content. No changes in pre- or post-I/R injury HSP expression were observed after GLN administration.


CONCLUSIONS
These observations demonstrate that remote in vivo administration of GLN before cardiac I/R injury can improve post-I/R cardiac function. This effect may be mediated via improved myocardial metabolism and enhanced reduced glutathione content.
Wischmeyer
Paul E
PE
Department of Anesthesiology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. paul.wischmeyer@UCHSC.edu
Jayakar
David
D
Williams
Ursula
U
Singleton
Kristen D
KD
Riehm
Jacob
J
Bacha
Emile A
EA
Jeevanandam
Valluvan
V
Christians
Uwe
U
Serkova
Natalie
N
D000244:Adenosine Diphosphate / Q000032:analysis; D000255:Adenosine Triphosphate / Q000032:analysis; D000409:Alanine / Q000008:administration & dosage; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000032:analysis; D005973:Glutamine / Q000008:administration & dosage*; D005978:Glutathione / Q000187:drug effects* / Q000378:metabolism*; D050884:HSP72 Heat-Shock Proteins; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000187:drug effects; D007275:Injections, Intravenous; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D008955:Models, Cardiovascular; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology*; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D009243:NAD / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D005973:Glutamine; D009243:NAD; D019344:Lactic Acid; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D005978:Glutathione; D005947:Glucose; D000409:Alanine