Resuscitation with lactated Ringer solution limits the expression of molecular events associated with lung injury after hemorrhage.
The aim of this study was to determine whether hemorrhage altered the caspase-3 activity and the ATP levels in rat lung and ileum tissues and determine whether resuscitation with lactated Ringer solution (LR) or whole blood (WB) reversed these changes. Male Sprague-Dawley rats were briefly anesthetized with isoflurane, and their mean arterial blood pressure was reduced from 110 to 40 mmHg by bleeding. The bled rat was then resuscitated with LR or autologous WB to bring mean arterial blood pressure back to 80 mmHg. Lung and ileum tissues were removed at the end of hemorrhage or at the end of the resuscitation period for specified bioassays. Hemorrhage increased cellular caspase-3 activity in the lung and the ileum. After the hemorrhaged rats received LR or WB, caspase-3 activity returned to the basal level in the lung and ileum, respectively. Likewise, hemorrhage decreased cellular ATP levels in lung and ileum. After LR or WB resuscitation, the cellular ATP level returned to the basal level only in the lung resuscitated with LR. The increased caspase-3 activity was associated with the increased expression of caspase-3 mRNA, which also returned to normal levels after either resuscitation. Similarly, hemorrhage increased the expression of inducible nitric oxide synthase and Kruppel-like factor 6 and decreased expression of Kruppel-like factor 4. Subsequent LR resuscitation normalized the expression of these genes in the lung tissue. Our results demonstrate that resuscitation with LR can reverse the expression of genes and their products that are thought to contribute to hemorrhage-induced lung injury.
Kiang
Juliann G
JG
Division of Military Casualty Research, Walter Reed Army Institute of Research, 503 Robert Grant Ave., Rm. 1N07, Silver Spring, MD 20910-7500, USA. Juliann.Kiang@na.amedd.army.mil
Lu
Xinyue
X
Tabaku
Lindita S
LS
Bentley
Timothy B
TB
Atkins
James L
JL
Tsokos
George C
GC
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001803:Blood Transfusion / Q000379:methods; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006470:Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D007552:Isotonic Solutions / Q000008:administration & dosage*; D000090062:Kruppel-Like Factor 4; D008171:Lung Diseases / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation / Q000379:methods*; D000077325:Ringer's Lactate; D014157:Transcription Factors / Q000378:metabolism; D016896:Treatment Outcome
D016207:Cytokines; D007552:Isotonic Solutions; C000715469:Klf4 protein, rat; D000090062:Kruppel-Like Factor 4; D000077325:Ringer's Lactate; D014157:Transcription Factors; D000255:Adenosine Triphosphate; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases