• Sen Hu, Jing-yuan Hou, Lin Li, Ming-xing Yang, and Zhi-yong Sheng.
• the First Affiliated Hospital of PLA General Hospital, Beijing, China. hs82080@yahoo.com.cn
• Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2011 Aug 1; 23 (8): 471-4.

ObjectiveTo investigate the effects of valproic acid (histone deacetylase inhibitor) on visceral function and outcome in a canine lethal hemorrhage model.MethodsTwenty male Beagle canines were subjected to an about 42% of total blood volume loss to reproduce a lethal hemorrhage shock model. Animals were randomly divided into shock control group (SC group) and valproic acid treatment group (VPA group), each group n=10. Canines in SC group and VPA group were intravenously injected either 20 ml saline or valproic acid (100 mg/kg) in 20 ml saline 1.5 hours after hemorrhage. Canines in each group were given delayed intravenous fluid resuscitation 24 hours after bleeding. The mean arterial pressure (MAP) was measured at 0 hour and at different time points without anesthesia, and the plasma levels of alanine aminotransferase (ALT), creatinine (Cr) and isoenzyme of creatine kinase (CK-MB) were measured before hemorrhage (0 hour), and at different time points after hemorrhage. Urinary output and survival rate 72 hours after hemorrhage were also recorded.ResultsThe levels of MAP in both groups were significantly lowered from 2 hours after bleeding. The level of MAP (mm Hg, 1 mm Hg=0.133 kPa) in VPA group recovered rapidly and exceeded with statistically significant difference compared with those of SC group after hemorrhage (4 hours: 58.4±7.6 vs. 40.3±5.0, 8 hours: 84.4±8.0 vs. 56.4±4.4, 24 hours: 92.6±10.3 vs. 72.6±8.9, P<0.05 or P<0.01). The amount of urinary output of VPA group was significantly higher than that of SC group during the period of 0-8 hours, 8-24 hours, 24-48 hours, and 48-72 hours, but it was still lower than that before hemorrhage (0 hour). The plasma parameters for visceral function in both groups were significantly elevated compared with 0 hour. The plasma levels of ALT, Cr and CK-MB in VPA group were obviously lower than those in SC group from 4 hours after hemorrhage [at 4 hours after bleeding, ALT (U/L): 80.1±9.8 vs. 112.2±10.1, Cr (μmol/L): 74.5±8.3 vs. 88.0±7.6, CK-MB (kU/L): 10.39± 1.10 vs. 13.67±1.46, P<0.05 or P<0.01], but the visceral functional parameters at 72 hours after hemorrhage in VPA group were obviously higher than those at 0 hour [ALT (U/L):79.5±7.1 vs. 40.5±4.4; Cr (μmol/L): 85.6±7.1 vs. 46.6±4.8; CK-MB (kU/L): 7.63±0.86 vs. 1.66±0.21, all P<0.01]. The survival rate of VPA group 72 hours after bleeding was significantly higher than that of SC group [70% (7/10) vs. 20% (2/10), P<0.05].ConclusionThe results indicate that intravenous injection of VPA promote MAP, increase urinary output, alleviate visceral injury and improve the survival rate at 72 hours in canines suffering from 42% blood volume loss, it might be an effective drug for hypovolemic shock, especially in war or other site of mass casualties in an austere environment.

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