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The Effect of Preventive Use of Alanyl-Glutamine on Diaphragm Muscle Function in Cecal Ligation and Puncture-Induced Sepsis Model

Nurcan Doruk, MD^*, Belgin Buyukakilli, PhD, Sebnem Atici, MD, PhD^*, Ismail Cinel, MD, PhD^*, Leyla Cinel, MD, Lulufer Tamer, PhD, Dincer Avlan, MD^||, Egemen Bilgin, MD^* and Ugur Oral, MD^*

From the ^* Departments of Anesthesiology and Reanimation, Biophysics, Pathology, Biochemistry, and^|| Pediatric Surgery, Mersin University School of Medicine, Mersin, Turkey

Correspondence: Nurcan Doruk, MD, Menderes Mh Bakanlik Cd Liparis Sitesi, F Blok 6/13 33280 Mezitli, Mersin, Turkey. Electronic mail may be sent to nurcan66{at}hotmail.com.

Background: Low muscle glutamine levels during sepsis are associated with reduced protein synthesis and elevated protein breakdown, in particular myofibrillar protein breakdown. Thus, in a cecal ligation and puncture (CLP)-induced sepsis model in the rat, we hypothesized that glutamine pretreatment would protect the diaphragm muscle function. Methods: Eighty-four male Wistar rats weighing between 180 g and 200 g received standard amino acid solution 1.2 g kg^–1 per day intraperitoneally (IP) or standard amino acid solution 1.2 g kg^–1 per day plus alanyl-glutamine (GLN) 0.25 g kg^–1 per day (IP) during the first 6 days of the experiment. On the seventh day, CLP or sham procedures were applied. The sham and CLP groups were equally divided into 3 subgroups according to the termination of the experiment, which took place at either the 24^th hour, 48^th hour, or 72^nd hour. After the compound muscle action potentials (CMAP) were recorded from the diaphragms of the rats at these selected times, they were decapitated under ketamine/xylazine anesthesia, and diaphragms were harvested for biochemical and histopathological examination. Results: The mean area and amplitude of CMAP were significantly larger in sham+GLN groups when compared with CLP and CLP+GLN groups at all times (p < .05). Diaphragm Ca⁺²-ATPase levels were found to be significantly decreased in CLP group at all times compared to sham groups (p < .05). Diaphragm reduced glutathione levels were significantly higher in sham+GLN groups when compared with CLP and CLP+GLN groups at all times (p < .05). In histopathologic assessment, moderate neutrophil infiltration, which was observed in CLP48, was significantly reduced with alanyl-glutamine supplementation in CLP+GLN48 group (p < .05). Conclusions: This study showed that glutamine pretreatment did not improve diaphragm muscle function, but prevented the biochemical and histopathological changes in diaphragmatic muscle in CLP-induced sepsis. However, further studies are needed to clarify whether a higher dose of glutamine supplementation might protect the diaphragmatic muscle functions.

Journal of Parenteral and Enteral Nutrition, Vol. 29, No. 1, 36-43 (2005)
DOI: 10.1177/014860710502900136


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