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Original Research: CRITICAL CARE MEDICINE |

N-Methyl-D-Aspartate Glutamate Receptor Blockade Attenuates Lung Injury Associated With Experimental Sepsis

Aline A. da Cunha, PharmD; Vânia Pauli, BSc; Vasyl C. Saciura, BSc; Melissa G. S. Pires, PhD; Leandra C. Constantino, BSc; Bruna de Souza, PharmD; Fabricia Petronilho, MSc; Jarbas Rodrigues de Oliveira, PharmD, PhD; Cristiane Ritter, MD, PhD; Pedro R. T. Romão, PhD; Carina Rodrigues Boeck, PhD; Rafael Roesler, PhD; João Quevedo, MD, PhD; Felipe Dal-Pizzol, MD, PhD
Author and Funding Information

From the Laboratório de Pesquisa em Biofísica Celular e Inflamação, Faculdade de Biociências (Drs da Cunha and Rodrigues de Oliveira, and Mss Pauli and Saciura), Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre; Laboratórios de Neurociências (Ms Constantino, and Drs Boeck and Quevedo), e Fisiopatologia Experimental (Drs de Souza, Romão, Ritter, and Dal-Pizzol; and, Ms Petronilho), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma; Department of Pharmacology (Dr Roesler), Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre; and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (Drs Roesler and Quevedo), Porto Alegre, Brazil.

Correspondence to: Felipe Dal-Pizzol, MD, PhD, Laboratório de Fisiopatologia Experimental, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil, Avenida Universitária, 1105, 88006-000; e-mail: piz@unesc.net


Funding/Support: This research was supported by the National Council for Scientific and Technological Development (CNPq) and UNESC. Dr Roesler is also supported by the South American Office for Anticancer Drug Development (SOAD; Porto Alegre, Brazil) and the Children’s Cancer Institute (ICI-RS; Porto Alegre, Brazil).

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).


© 2010 American College of Chest Physicians


Chest. 2010;137(2):297-302. doi:10.1378/chest.09-1570
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Background:  The aim of this study was to examine the effects of the N-methyl-D-aspartate receptor (NMDAR) channel blocker dizocilpine (MK-801) on lung injury in rats submitted to experimental sepsis induced by cecal ligation and perforation (CLP).

Methods:  Adult male Wistar rats submitted to CLP were given a single systemic injection of MK-801 (subcutaneously at 0.3 mg/kg) administered 4 or 7 h after CLP induction. Twelve hours after CLP BAL was performed to determine total cell count, protein content, and inflammatory parameters. In addition, lung was excised for histopathologic analyses and determination of NMDAR subunits content. In a separate cohort of animals mortality was recorded for 5 days.

Results:  Animals submitted to sepsis induced by CLP showed an increase in the content of NMDAR subunits NR1 and NR2A in the lung. Administration of MK-801 4 h after CLP induction resulted in a decrease in BAL fluid cellular content and decreased levels of proinflammatory cytokines. In addition, MK-801 decreased lung oxidative stress markers and histopathologic alterations and improved survival.

Conclusions:  These findings indicate that NMDAR blockade might represent a promising novel therapeutic strategy for the treatment of sepsis and inflammatory disorders.

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