Effects Of Dobutamine Combined With Vasopressin On Intestinal Injury In Rats With Septic Shock

Objective In the treatment of septic shock, the application of vasoactive drugs is one of the most important measures. While the hypotension was corrected, gastro and intestinal ischemia is existence sustainably. Intestine is the organ which is not only to be damaged vulnerably in septic shock, but also have an significant impact on the development of shock. Gastrointestinal ischemia and hypoxia are important reasons of multi-organ dysfunction syndrome (MODS). Therefore, the evaluation of vasoactive drugs to increase blood pressure should not be a simple subject, but should also be concerned about whether improved tissue perfusion. In this study, we observed the effects on gastrointestina injury with norepinephrine, dopamine, arginine vasopressin and dobutamine combined with arginine vasopressin based on fluid resuscitation in septic shock rats.Methods Fifty healthy male SD rats weighing 250-300 g, were randomized into 5 groups (n=10):normal saline group (NS group), noradrenaline group (NE group), dopamine group (DA group), arginine vasopressin group (AVP group), and dobutamine combined with arginine vasopressin group (DOB+AVP group). After establishing the septic shock model via the injection of lipopolysaccharide 15 mg/kg, normal saline 10 ml·kg-1·h-1 was intravenously infused for volume resuscitation together with the same volume of NS, NE 1μg·kg-1·min-1, DA 10μg·kg-1·min-1, AVP 0.04 U·kg-1·min-1, and DOB 10μg·kg-1·min-1 combined with AVP 0.04 U·kg-1·min-1. The doses of pressors were adjusted to maintain systolic arterial pressure around 90 mmHg. Record the blood lactate concentrations from arterial blood gas analysis at the time before model was built, after model was built and model was killed respectively. Four hours later, intestinaltissue was obtained to detect the levels of TNF-α, IL-6 and IL-10 with ELISA, the levels of iNOS, MDA and SOD with chemistry colorimetric methods and observe the injury degree of intestinal tissue with microscope and mitochondria with electron microscope.Results After the injection of lipopolysaccharide 15 mg/kg, the systolic arterial pressure was declined and the blood lactate concentration was increased (P<0.05). The blood lactate concentrations in DOB+AVP group was lower than the other four groups (P<0.05). The levels of intestinal TNF-a and IL-6 were significantly lower in DOB+ AVP group and NE group than NS group, DA group, and AVP group (P<0.05). IL-10 had no significant difference between groups. The level of iNOS, SOD of intestinal tissue in DOB+AVP group were significantly higher than the other four groups (P<0.05) and the content of MDA was lower than the other four groups (P<0.05). The level of iNOS in AVP group was higher than the other 3 groups (P<0.05). The content of SOD in DA group was higher than NE group (P<0.05). DOB+AVP group had less injury of intestinal tissue and mitochondria than the other four groups.Conclusion In the treatment of septic shock, DOB combined with AVP can decrease the blood lactate concentrations, reduce the intestinal inflammatory responses and oxidative Stress, lessen the injury of intestinal tissue and mitochondria.