cDNA array analysis of gene expression following hemorrhagic shock and resuscitation in rats

The aim of this study was to characterize gene expression following hemorrhagic shock and resuscitation with emphasis on the differences between various resuscitation strategies.

Male Sprague Dawley rats (n = 25; 5/group) were subjected to a three stage hemorrhage and resuscitated as follows: (1) sham hemorrhage; (2) sham resuscitation; (3) lactated Ringer's solution (LR), 3:1 volume; (4) 7.5% hypertonic saline (HTS) 9.7 ml/kg; (5) plasma, 1:1 volume. Liver, spleen, lung and muscle were collected 3 h post resuscitation and cDNA array analysis was performed on the total RNA.

Expression of 1,176 genes was analyzed. Following resuscitation, 82 of the genes studied (7%) displayed an altered expression of at least 2-fold compared to the sham hemorrhage group. Depending on organ system under study and resuscitation conditions, expression of these 82 genes was down- or up-regulated, bringing the total number of expression alterations to 167. Largest number of organ-specific changes in gene expression was noted in liver (63/167), followed by lung (57), muscle (25), and spleen (22). Most of the resuscitation strategy specific changes were caused by plasma resuscitation (68/167), followed by LR (51), and HTS (48). In every organ studied, gene expression profile was dependent upon the fluid used for resuscitation.

Cellular response to hemorrhagic shock, even at the level of gene expression, is dependent on the resuscitation strategy. We have discovered altered expression of genes not previously implicated in the physiology of hemorrhagic shock and resuscitation. Gene array technology provides a rapid and efficient means of dissecting the complex genetic regulation of cellular response to shock.