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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Goal-directed therapy with dopexamine, dobutamine, and volume expansion: effects of systemic oxygen transport on hepatic ultrastructure in porcine sepsis.

OBJECTIVES: Can the hepatic structural deterioration that occurs during peritonitis be attenuated by increasing cardiac output and oxygen consumption (VO2)? Do the agents used to achieve these increases have any characteristic affects on these hepatic structural changes? DESIGN: Randomized, prospective, observational animal study. SETTING: Research laboratory of a university medical school. SUBJECTS: Twenty-five Middle White adolescent pigs, weighing 25 to 30 kg, divided into five groups. INTERVENTIONS: A thermodilution flotation catheter was advanced into the pulmonary artery. Additional catheters were inserted into the jugular, portal, and hepatic veins, and into the femoral artery. Ultrasound flow probes were placed around the portal vein and the hepatic artery. A metabolic cart was attached to the ventilator. Baseline measurements were made and cardiac output was increased by > 25% by administering either dobutamine (10 micrograms/min), dopexamine (10 micrograms/kg/min), or colloid. A control group had its cardiac output maintained at its baseline value. Peritonitis was induced in the four groups by contamination with cecal content and maintained for 6 hrs. Hepatic tissue was then removed for ultrastructural analysis and the animals were killed. MEASUREMENTS AND MAIN RESULTS: Before infection, cardiac output, VO2, and hepatic blood flow were increased in the three treatment groups. In the dobutamine and dopexamine groups, oxygen delivery increased, but decreased in the volume group. Mean arterial pressure increased in the dobutamine and dopexamine groups, but in the volume group, mean arterial pressure was maintained. Six hours after infection, cardiac output and VO2 had further increased in the dobutamine and volume groups, but both variables had decreased in the dopexamine group. After infection in the control group, cardiac output had decreased, although oxygen delivery and VO2 increased. There were no significant differences between hepatic hemodynamic or oxygen transport variables in any of the groups during the infection period. Hepatic ultrastructure was well maintained in the dopexamine group, while considerable deterioration was seen in the volume and control groups. In the dobutamine group, hepatic deterioration was greater than in the other three groups. CONCLUSIONS: Increasing cardiac output and VO2 before and during infection was only protective when dopexamine was administered. Dobutamine infusion was associated with greater hepatic deterioration than that effect seen in either the control or volume groups.[1]


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