v.) H2S prevented death and lethal hypoxia in rats subjected to controlled but unresuscitated hemorrhage.Conversely, Mok et al. [17] reported the hemodynamic effects of the inhibition of H2S synthesis, along with a rapid restoration in mean arterial more info pressure (MAP) and heart rate (HR), in a model of unresuscitated hemorrhage in rats.As the vascular effects of H2S are still a matter of debate, and since all of these data originated from unresuscitated hemorrhage, we therefore tested the hypothesis that the H2S donor sodium hydrosulfide (NaHS), infused before retransfusion in a model of a controlled hemorrhagic rat, may improve hemodynamics and attenuate oxidative and nitrosative stresses, as well as the inflammatory response during reperfusion.

Since the role of the cardiovascular system during shock becomes critical, we therefore focused on the inflammatory response as well as on the oxidative and nitrosative stresses in the heart and aorta.Materials and methodsThe animal protocol was approved by the regional animal ethics committee (CREEA-Nantes, France). The experiments were performed in compliance with the European legislation on the use of laboratory animals.AnimalsAdult male Wistar rats, weighing 325 �� 15 g, were housed with 12-hour light/dark cycles in the animal facility of the University of Angers (France).Surgical procedureAnimals were anesthetized with intraperitoneal pentobarbital (50 mg/kg of body weight) and placed on a homeothermic blanket system in order to maintain rectal temperature between 36.8��C and 37.8��C throughout the experiment.

After local anesthesia with lidocaine 1% (Lidocaine? 1% AstraZeneca, Reuil-Malmaison, France), a tracheotomy was performed. Animals were mechanically ventilated (Harvard Rodent 683 ventilator, Harvard Instruments, South Natick, MA, USA) and oxygen was added in order to maintain PaO2 above 100 mmHg. The left carotid artery was exposed, and a 2.0 mm transit-time ultrasound flow probe (Transonic Systems Inc., Ithaca, NY, USA) was attached to allow continuous measurement of blood flow (CBF).After local anesthesia, the femoral artery was canulated both to measure MAP and HR and for the induction of hemorrhagic shock. The homolateral femoral vein was canulated for retransfusion of shed blood, for fluid maintenance and for bolus infusion (either vehicle or NaHS).

Induction of hemorrhagic shock and protocol designAfter a 20-minute stabilization period, controlled hemorrhage [18] was induced by withdrawing approximately 9 ml of blood collected in a heparinized syringe (200 UI) within 10 minutes until MAP decreased to 40 �� 2 mmHg. This state of controlled hemorrhage was maintained during 60 minutes by further blood GSK-3 withdrawal or reinfusion of shed blood. Ten minutes prior to retransfusion time, rats were randomly allocated to receive either NaHS (single i.v. bolus 0.2 mg/kg body weight) or control (vehicle 0.