Acute therapeutic use of 5-aminoimidazole-4-carboxamide ribonucleoside extends survival interval in response to severe hemorrhagic shock

This study tests the hypothesis that pretreatment and/or posttreatment with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), an inducer of adenosine monophosphate-activated protein, will extend the golden hour of survival time in rats subjected to severe hemorrhagic shock in the absence of available fluid resuscitation. Three days before hemorrhage, at 24-h intervals, animals were given three i.p. injections of AICAR (pretreatment) or saline (control/posttreatment). At the end of hemorrhage, animals (control/pretreatment) received a single i.v. injection of saline, whereas the posttreatment group received a single i.v. injection of AICAR (posttreatment). All treatment groups received the same total volume of fluid both before and immediately after hemorrhage. Both AICAR treatment groups had significantly(P < 0.01) extended survival time during the decompensatory phase of shock when compared with saline control group, pretreatment: 324 ± 21 min; posttreatment: 187 ± 16 min; and saline: 55 ± 10 min. Heart rate was significantly (P < 0.01) decreased following hemorrhage for pretreatment animals versus saline controls, 237 ± 16 vs. 312 ± 33 beats/min, respectively. Heart rate for both the pretreatment and posttreatment animals was also significantly (P < 0.01) lower after 30 min versus saline control group, pretreatment: 247 ± 13 beats/min; posttreatment: 240 ± 20 beats/min; saline: 415 ± 18 beats/min. Lactate levels were also significantly reduced 6.3 ± 0.71 mmol/L (pretreatment), 7.1 ± 0.47 mmol/L (posttreatment), 8.9 ± 0.21 mmol/L (saline). The improvement in hemodynamic stability is reflected in the significant increase in the golden-hour survival time in animals subjected to severe hemorrhagic shock.