Crush Injury and Simulated Flight Effects on Muscle Gene Expression in Female Mice.

BACKGROUND: Aeromedical evacuation provides critical care during long-distance transport of injured victims between medical facilities. Often, these victims sustain muscle trauma related to mechanical insults, such as crush. Understanding the effects of flight on injured muscle is important because the aircraft cabin represents an external environment with mild hypoxia-the cabin's altitude is 2,438 m instead of sea level. Since mild hypobaric hypoxia can alter gene expression in normal muscle and affect recovery patterns, it is beneficial to examine whether this type of hypoxia may also alter injury-related genes.

OBJECTIVE: The objective of this study was to verify the hypothesis that differential gene expression occurs in response to mild hypobaric hypoxia exposure in crush-injured muscle during two early recoveries (pre-regeneration stage) time points.

METHODS: Twenty-four female mice were anesthetized, and the right gastrocnemius muscle underwent crush injury. Approximately 24 hr later, mice were exposed to normobaric normoxia or hypobaric hypoxia for 8-9 hr. After 32 hr or 48 hr of recovery, the mice were euthanized, and the right and left lateral gastrocnemius muscles were collected for microarray and bioinformatics analyses.

RESULTS: The study hypothesis was verified. There were 353 highly upregulated, differentially expressed genes identified in the injured muscle compared to the uninjured muscle. Mid1 was differentially upregulated in both pressure conditions regardless of injury status. There were 52 and 15 differentially expressed genes at 32 hr and 48 hr postinjury, respectively, in the hypobaric hypoxia-exposed, injured muscle compared to the normobaric normoxia-exposed, injured muscle-the macrophage gene, Cd68, correlated with other leukocyte-related.

DISCUSSION: These findings expand our understanding of the genetic changes that occur in muscle in response to a crush injury, including those related to the macrophage protein, Cd68. Nursing interventions addressing adequate functioning after crush muscle injury may need to consider the effects on Cd68 and its closely related genes. Additionally, our results suggest a responsiveness of the gene, Mid1, to flight-relevant hypobaric hypoxia. Changes in expression of Mid1 may be appropriate in assessing the long-term health of flight crew members.