Effect of initial fluid resuscitation on subsequent treatment in uncontrolled hemorrhagic shock in rats

Using a modified uncontrolled hemorrhage shock model with massive splenic and vascular injury, we evaluated outcome and tissue oxidation injury with different resuscitation interventions during prehospital and hospital phases. The aim of our study was to explore the effect of initial fluid resuscitation on subsequent treatment of uncontrolled hemorrhagic shock in rats. Uncontrolled hemorrhagic shock was produced in 114 Wistar rat by sharp transection both of the splenic parenchyma at one location between the major branches of the splenic artery into the spleen and of one of the major branches of the splenic artery. Experimental design consisted of three phases: a "prehospital phase" (resuscitation with balanced saline to a mean arterial pressure (MAP) of 40, 50, 60, 80, and 100 mmHg, respectively, when MAP reached 30 mmHg), followed by a "hospital phase" (120 min, including control of hemorrhage and resuscitation with balanced saline and whole blood (2:1) or balanced saline alone to a MAP >80 mmHg), and a 240-min observation phase. Blood loss, infused volume, hematocrit, and survival rate were recorded. At the end of the experiment, survivors were sacrificed, and the lung, kidney, and distal ileum were harvested for determination of malondialdehyde (MDA) content and total antioxidative capacity (T-AOC). All rats that were resuscitated to a MAP >80 mmHg in the prehospital phase and received balanced saline alone in the hospital phase died, whereas those that had been resuscitated to a MAP of 40 or 50 mmHg during the prehospital phase and then resuscitated with balanced saline and whole blood in the hospital phase survived throughout the experiment. The animals whose MAP was kept higher than 80 mmHg had significantly higher MDA content and lower T-AOC than those whose MAP was maintained 40, 50, or 60 mmHg during the prehospital phase. In the hospital phase, resuscitation with balanced saline and whole blood not only relieved tissue damage but also improved the survival, as indicated by 44.4% survival rate in the rats that resuscitated to a MAP of 80 or 100 mmHg in the prehospital phase. These results suggested that in our uncontrolled hemorrhagic shock model, limited resuscitation in the prehospital phase had benefit for subsequent treatment in the hospital phase in terms of alleviated tissue damage and improved survivorship.