Perioperative application of l-alanyl-l-glutamine in cardiac surgery: effect on the polarized T cell cytokine expression

Abstract

At risk patients undergoing cardiac surgery with cardiopulmonary bypass have increased rates of postoperative infectious morbidity. Postoperatively, after cardiac surgery, an immunosuppression in the form of a polarization of T helper (Th) cells with a decreased Th1 response (IL-2 and IFN-gamma) and an increased Th2 response (IL-4 and IL-10) is recognized. Therapeutic strategies to modulate the immunological response include special key nutrients such as the amino acid glutamine favoring the Th2 response. There is no information available concerning its effect in patients undergoing cardiac surgery. The aim of this clinical study was to evaluate the effects of a perioperative infusion of glutamine on the polarized lymphocyte T cell cytokine expression and on infectious morbidity in cardiac surgery patients at risk of infection. Seventy-eight patients were included in the study undergoing elective cardiac surgery with a lymphopenia less than 1.2 giga/l. One or more of the following criteria had to be met: age older than 70 years, ejection fraction less than 40%, or mitral valve replacement. We randomly assigned patients to receive infusions of either high-dose L-alanyl-L-glutamine dipeptide [0.5 g/(kg day) glutamine] dissolved in an amino acid solution or an isonitrogeneous, isocaloric, isovolemic nutritional solution. An additional group with normal saline served as control to eliminate any nonspecific nutritional effect. We started the infusion after induction of anesthesia with 1,000 ml/24 h and continued it for 3 days. The primary endpoint was intracellular T cell cytokine expression (including the description in tertiles) on the first postoperative day (pod 1). Secondary endpoints were postoperative infection rate, mortality rate, cardiovascular circulation ventilation time, and renal function. A high-dose perioperative glutamine application leading to mean plasma levels of 1,177 microM had only a minor influence on the polarized intracellular T cell cytokine expression. On pod 1 there was a polarization of T cells, i.e., an augmented Th2 response with an increased number of IL-6 and IL-10 producing cells. On the other side the Th1 response with IL-2 and TNF-alpha declined on pods 1 and 2. Only the intracellular IL-2 response in the lower tertile of IL-2 production was improved with glutamine indicating a small influence. We did not observe any effects on the numbers of postoperative infections; on mortality rate; on cardiovascular circulation; on ventilation time or on renal function. The elevation of glutamine plasma levels by a perioperative intravenous infusion of L-alanyl-L-glutamine influenced the intracellular expression of IL-2 in the lower tertile only slightly. However, mean glutamine values in the other groups remained above or close 500 microM, thus suggesting that glutamine supply to the immune cells was still adequate in most patients, and that glutamine deficiency, if it occurred, was marginal. In the event of a severe glutamine deficiency the observed effect on cytokine production could be mor...

Glutamine promotes antibiotic uptake to kill multidrug-resistant uropathogenic bacteria

“…l -alanyl- l -glutamine has been widely used in clinic as a way to provide l -glutamine ( 33 ). Infusion with l -alanyl- l -glutamine (0.5 g/kg) per day has been reported ( 34 ). The highest dose of glutamine we used in vivo in this study was 100 mg/kg, much lower than the reported dose.…”

The Preventive Role of Glutamine Supplementation in Cardiac Surgery-Associated Kidney Injury from Experimental Research to Clinical Practice: A Narrative Review

“…The researchers used a high-dose L-alanyl-Lglutamine dipeptide (L-ALA-GLN) (0.5 g/kg/day GLN) after induction of anesthesia and continued it for three days. This action had only a minor influence on intracellular IL-2 and the expression of polarized intracellular T cell cytokine [93], and no effect on intracellular IL-1, IL-6, IL-8, and TNFα [92]. No other effects on C-reactive protein (CRP) level [92], mortality rate [93], postoperative infections number [93], vasopressor/inotropic support [92], ventilation time [92,93], renal function [93], SOFA score [92], and ICU length of stay [92] were found [93].…”

“…Engel et al ( 2009) studied the GLN supplementation in open cardiac surgery patients that fulfilled one of the following criteria: age over 70 years, ejection fraction less than 40%, or mitral valve replacement [91][92][93]. The researchers used a high-dose L-alanyl-Lglutamine dipeptide (L-ALA-GLN) (0.5 g/kg/day GLN) after induction of anesthesia and continued it for three days.…”

Nutritional Effect of Oral Supplement Enriched in ω-3 Fatty Acids, Arginine, RNA on Immune Response and Leukocyte–platelet Aggregate Formation in Patients Undergoing Cardiac Surgery

“…Markewitz et al found that IL-2 and IFN-γ secretion are diminished after cardiac surgery;15 conversely, Muret et al demonstrated that IL-4 and IL-10 production are elevated 16. Thus, the Th1 and Th2 responses are decreased and increased, respectively, after cardiac surgery 17. Fatty acids are classified into two main families of polyunsaturated fatty acids; ω-3 fatty acids, which include eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and the other is ω-6 fatty acids, which include linoleic acid (LA), arachidonic acid (AA), and γ-linolenic acid.…”

“…16 Thus, the Th1 and Th2 responses are decreased and increased, respectively, after cardiac surgery. 17 Fatty acids are classified into two main families of polyunsaturated fatty acids; ω-3 fatty acids, which include eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and the other is ω-6 fatty acids, which include linoleic acid (LA), arachidonic acid (AA), and γ-linolenic acid. Several studies have reported beneficial effects of preoperative supplementation with specialized diets enriched with ω-3 fatty acids, arginine, and RNA.…”