Oral Glutamine Reduces Myocardial Damage After Coronary Revascularization Under Cardiopulmonary Bypass

INTRODUCTION Glutamine (GLN) is the most abundant free amino acid in the body, and commonly known as a non-essential amino acid due to the ability of most cells to produce it. It has many essential metabolic functions in the organism; it is an energy substrate for most cells (especially for enterocytes and lymphocytes), a precursor for nucleotide, glutamate, and (in particular) glutathione synthesis, and an important cellular antioxidant. It plays a central role in nitrogen transport within the body, and is the most important substrate for renal ammoniagenesis.

Studies have demonstrated that the presence of GLN in the medium regulates glutamine synthetase expression via a post-transcriptional mechanism, where the rate of glutamine synthetase protein degradation is diminished and its activity, augmented, in the presence of low GLN concentration. This amino acid modulates immune cell function and production of cytokines via attenuation of multiple pathways of inflammation, such as Nuclear Factor kB (NF-kB), protein kinases, inhibition of increases in Nitric Oxide Synthase (iNOS) expression.

It has been shown to be beneficial for the metabolically stressed patient, especially the critically ill patients. During acute illnesses, patients experience nutritional depletion, which correlates with low plasma and low mucosal GLN concentrations.

GLN levels are significantly decreased in critical illness, leading to an increase in infectious complications, organ failure and mortality. Moreover, in cases of ischemia/reperfusion injury, GLN increases the myocardial ATP/ADP ratio and prevents intracellular lactate accumulation.

GLN has been shown to be a key nutrient in the body's response to stress and injury described in multiple studies with in vitro and in vivo myocardial injury following I/R. These include enhanced myocardial glutathione, adenosine triphosphate (ATP), and glutamate (a major stress substrate for the stressed myocardium) post-I/R injury, and induction of heat shock proteins, especially Heat Shock Protein-70 (HSP-70) in critically ill patients. The stress tolerance provided by HSP-70 can protect against cellular injury, lung injury, ischemia/reperfusion injury, and septic shock, by the GLN influences on the inflammatory response, oxidative stress, apoptosis modulation, and the integrity of gut barrier.