Article Figures & Data
Figures
- Figure 1
Model of injuries. Animals were subjected to a 40% total blood volume hemorrhage, followed by a period of unresuscitated shock, and then treated with various histone deacetylase inhibitors. They were then observed for a period of 3 hours prior to euthanasia and sample collection. BL, baseline; NEC, necropsy; PH, posthemorrhage; PS, postshock; TBV, total blood volume.
- Figure 2
Effect of each HDACI treatment on HS-induced IL-1β levels in the (A) intestine and (B) serum. HS resulted in a significant increase in the levels of IL-1β in both the intestine and serum as compared with sham. In the intestine, treatment with each of MC (p<0.0001), ACY (p<0.0001), MC+ACY (p=0.0001), and VPA (p<0.05) significantly decreased the expression of IL-1β compared with the vehicle. Expression of IL-1β in the intestine was significantly lower in the animals treated with ACY compared with VPA (p<0.05). In the serum, treatment with MC (p<0.0001), ACY (p<0.0001), MC+ACY (p<0.0001), and VPA (p<0.01) significantly decreased the expression of IL-1β compared with the vehicle. Expression of IL-1β in the serum was significantly lower in each of the MC and ACY groups as compared with the VPA group (p<0.01). ACY, ACY1083; HDACI, histone deacetylase inhibitor; HS, hemorrhagic shock; IL-1β, interleukin 1 beta; MC, MC1568; NS, normal saline vehicle; VPA, valproic acid; * denotes significance between groups (p<0.05).
- Figure 3
Effect of each HDACI treatment on HS-induced TNF-α levels in the (A) intestine and (B) serum. HS resulted in a significant increase in the levels of TNF-α in both the intestine and serum as compared with sham. In the intestine, treatment with each of MC (p<0.0001), ACY (p<0.0001), MC+ACY (p<0.0001), and VPA (p<0.01) significantly decreased the expression of TNF-α compared with the vehicle. Expression of TNF-α in the intestine was significantly lower in the animals treated with MC and ACY as compared with VPA (p<0.001). In the serum, treatment with MC (p<0.0001), ACY (p<0.0001), and MC+ACY (p<0.001) significantly decreased the expression of TNF-α compared with the vehicle. The expression of TNF-α in the serum was significantly lower in the MC and ACY groups as compared with the VPA group (p<0.01). ACY, ACY1083; HDACI, histone deacetylase inhibitor; HS, hemorrhagic shock; MC, MC1568; NS, normal saline vehicle; TNF-α, tumor necrosis factor alpha; VPA, valproic acid; * denotes significance between groups (p<0.05).
- Figure 4
Effect of each HDACI treatment on HS-induced levels of CINC-1 in the intestine. HS significantly increased the expression of CINC-1 as compared with sham. Treatment with each of MC (p<0.01), ACY (p<0.001), and MC+ACY (p=0.01) significantly decreased intestinal CINC-1 expression compared with the vehicle. There was no significant difference in intestinal CINC-1 expression between the VPA and vehicle groups (p>0.05). ACY, ACY1083; CINC-1, cytokine-induced neutrophil chemoattractant 1; HDACI, histone deacetylase inhibitor; HS, hemorrhagic shock; MC, MC1568; NS, normal saline vehicle; VPA, valproic acid; * denotes significance between groups (p<0.05).
- Figure 5
Effect of each HDACI treatment on HS-induced intestinal c-caspase 3 expression. HS significantly increased the expression of c-caspase 3 compared with sham. Treatment with each of MC (p<0.0001), ACY (p<0.0001), MC+ACY (p<0.0001), and VPA (p=0.0003) significantly decreased the levels of c-caspase 3 in the intestine compared with the vehicle. Animals in MC (p=0.01) and ACY (p=0.001) groups had significantly lower levels of c-caspase 3 compared with the VPA group. ACY, ACY1083; c-caspase 3, cleaved caspase 3; HDACI, histone deacetylase inhibitor; HS, hemorrhagic shock; MC, MC1568; NS, normal saline vehicle; VPA, valproic acid; * denotes significance between groups (p<0.05).
- Figure 6
Effect of each HDACI treatment on histopathologic evidence of intestinal injury. Hemorrhagic shock resulted in significant blunting and shortening of the villi, capillary congestion, focal epithelial surface necrosis, and infiltration of inflammatory cells in the lamina propria. Treatment with each of the MC (p<0.05), ACY (p<0.05), and MC+ACY (p<0.05) groups attenuated these changes compared with the vehicle. No significant difference was seen between the VPA group and the vehicle group (p=0.4). ACY, ACY1083; HDACI, histone deacetylase inhibitor; MC, MC1568; NS, normal saline vehicle; VPA, valproic acid; * denotes significance between groups (p<0.05).
Tables
- Table 1
Select laboratory data
Timepoint Variable Group Baseline End of shock Weight (g) Vehicle 272.±11.4 – MC1568 276.3±7.4 – ACY1083 279.5±10.0 MC1568+ACY1083 270.5±11.7 VPA 278.0±8.3 Cannulation time (min) Vehicle 13.3±1.7 – MC1568 15.0±1.6 ACY1083 15.5±2.3 – MC1568+ACY1083 18.5±1.0 VPA 13.5±1.5 MAP (mm Hg) Vehicle 94.9±1.5 50.8±3.5* MC1568 92.2±5.4 49.1±1.3* ACY1083 92.7±7.2 53.7±4.2* MC1568+ACY1083 93.3±4.4 53.8±2.3* VPA 94.1±4.5 57.9±2.9* Lactate (mmol/L) Vehicle 1.4±0.1 4.3±1.0* MC1568 1.5±0.2 4.9±0.6* ACY1083 1.3±0.1 4.7±0.5* MC1568+ACY1083 1.2±0.1 4.5±0.3* VPA 1.3±0.2 4.3±0.6* *Significant difference compared with the baseline value of the same group (p<0.05).
MAP, mean arterial pressure; VPA, valproic acid.
