Patients that survive hemorrhage and resuscitation (H/R) may develop a systemic inflammatory response syndrome (SIRS) that leads to dysfunction of vital organs (multiple organ dysfunction syndrome, MODS). SIRS and MODS may involve mitochondrial dysfunction. Under pentobarbital anesthesia, C57BL6 mice were hemorrhaged to 30？mm？Hg for 3？h and then resuscitated with shed blood plus half the volume of lactated Ringer’s solution containing minocycline, tetracycline (both 10？mg/kg body weight) or vehicle. Serum alanine aminotransferase (ALT), necrosis, apoptosis and oxidative stress were assessed 6 h after resuscitation. Mitochondrial polarization was assessed by intravital microscopy. After H/R with vehicle or tetracycline, ALT increased to 4538？U/L and 3999？U/L, respectively, which minocycline decreased to 1763？U/L ( ). Necrosis and TUNEL also decreased from 24.5% and 17.7 cells/field, respectively, after vehicle to 8.3% and 8.7 cells/field after minocycline. Tetracycline failed to decrease necrosis (23.3%) but decreased apoptosis to 9 cells/field ( ). Minocycline and tetracycline also decreased caspase-3 activity in liver homogenates. Minocycline but not tetracycline decreased lipid peroxidation after resuscitation by 70% ( ). Intravital microscopy showed that minocycline preserved mitochondrial polarization after H/R ( ). In conclusion, minocycline decreases liver injury and oxidative stress after H/R by preventing mitochondrial dysfunction. 1. Introduction Trauma and surgical procedures, including gastrointestinal and hepatobiliary surgery, can lead to severe hemorrhage and hypovolemic shock. Fluid resuscitation after less than one hour of severe hemorrhagic shock restores hemodynamics and typically leads to full recovery. By contrast although restoring hemodynamics, resuscitation after greater than an hour may lead instead to multiple organ dysfunction syndrome (MODS), which is associated with mortality of 30% [1]. Effective strategies to extend this golden hour for resuscitation are therefore needed to improve the treatment of hemorrhagic shock and decrease the incidence of MODS and its lethal consequence. Hemorrhage/resuscitation (H/R) is an example of ischemia/reperfusion (I/R) and hypoxia/reoxygenation injuries, for which mitochondrial dysfunction plays a major pathophysiological role [2–4]. Moreover, the liver with its crucial involvement in metabolism and homeostasis is among the most frequently affected organs after hemorrhage-induced hypotension in humans [5]. I/R injury leads to both necrotic cell death and apoptosis. A common pathway for
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