Key result
Fixed-volume hemorrhage in rats resulted in statistically detectable alteration of expression in approximately 0.8% of the 5,671 lung genes tested over a 72-hour period compared to sham hemorrhage.
Gene expression profiling with microarrays demonstrates that severe systemic blood loss alters the expression of genes regulating intracellular signaling, structure, and immune cell sequestration in the lung.
Hemorrhage-induced rat lung gene changes are hypothesis-generating; leaves open clinical relevance and need for human validation.
Previous studies have indicated that hemorrhage may predispose the lung to respiratory distress syndrome. Gene expression profiling with oligonucleotide microarrays was used to evaluate the genetic responses of the lung to hemorrhage. Conscious rats, chronically instrumented with a catheter and telemetry device to record blood pressure, heart rate, and temperature, had 40% of their estimated blood volume removed at a rate of 1 ml/min over 7-10 min. Groups of three or more rats were euthanized at 1, 3, 6, 16, 24, 48, or 72 h following hemorrhage. Two additional groups were unmanipulated controls and instrumented animals with sham hemorrhage. Total RNA was isolated from lung, reverse-transcribed to cDNA, fluorescently labeled, and hybridized to oligonucleotide microarrays probing 5,671 rat genes. After hemorrhage, statistically detectable alteration of expression was seen in approximately 0.8% of the genes at some time during the 72-h test period (vs. sham hemorrhage) as determined by false discovery rate statistics in the statistical analysis of microarrays program. A subset was confirmed by RT-PCR analysis. Hemorrhage influenced genes that regulate intracellular signaling and structure, growth factors, and hormonal receptors. There also appeared to be increased expression of genes that may mediate sequestration of neutrophils and mononuclear cells from the circulation. This hemorrhage model, although producing severe hemodynamic alterations, avoided mortality and histological evidence of lung damage, a feature intended to help ensure reliable evaluation of gene expression. These results indicate that gene expression profiling with microarrays provides a new tool for exploring the response of a tissue to systemic blood loss.
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Bowman et al. (2005) studied Hemorrhage. Fixed-volume hemorrhage vs. Unmanipulated controls and sham hemorrhage was evaluated on Alteration of gene expression in the lung. Fixed-volume hemorrhage in rats resulted in statistically detectable alteration of expression in approximately 0.8% of the 5,671 lung genes tested over a 72-hour period compared to sham hemorrhage.
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