Effect of dobutamine infusion on endotoxin-induced lipid peroxidation in awake sheep.
beta-agonists are known to not only increase oxygen delivery, but also attenuate the inflammatory response. We studied the effect of infusing the beta-agonist, dobutamine, on the oxidant-induced lung and liver tissue lipid peroxidation seen after endotoxemia. Twelve unanesthetized adult sheep with lung and soft tissue (prefemoral) lymph fistulae were given 5 micrograms/kg of Escherichia coli endotoxin intravenously. In six sheep, dobutamine 10 to 15 micrograms/kg/min was infused beginning 3 hours after endotoxin to increase oxygen delivery by 75% above baseline. Animals were killed at 6 hours, and lung and liver lipid peroxidation, measured as malondialdehyde, was obtained. Data were compared to six control sheep. Endotoxin alone produced increased lung and soft tissue vascular permeability as evidenced by a twofold increase in protein-rich lymph flow. Lung and liver malondialdehyde increased to 116 +/- 40 nmol/gm and 202 +/- 64 nmol/gm, respectively, compared to control values of 42 +/- 7 nmol/gm and 110 +/- 20 nmol/gm, respectively. Dobutamine infusion after endotoxin increased oxygen delivery by 75%, although changes in total oxygen consumption were not different from those seen with endotoxin alone. Lung and soft tissue lymph flow did not change with dobutamine. However, lung malondialdehyde was 41 +/- 17 nmol/gm, not different from controls. Liver malondialdehyde remained elevated at 164 +/- 26 nmol/gm. We conclude that dobutamine infusion prevents further oxidant-induced lung tissue lipid peroxidation but does not reverse the increased permeability already present. Liver lipid peroxidation was not decreased, suggesting the liver oxidant process may not be caused by the same mechanism as the lung lipid peroxidation.
Demling
R H
RH
Longwood Area Trauma Center, Boston, MA 02115.
Knox
J
J
Youn
Y K
YK
Daryani
R
R
LaLonde
C
C
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury; D004280:Dobutamine / Q000494:pharmacology*; D004731:Endotoxins / Q000494:pharmacology; D005260:Female; D007262:Infusions, Intravenous; D015227:Lipid Peroxidation / Q000187:drug effects*; D008107:Liver Diseases / Q000378:metabolism* / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D012756:Sheep
D004731:Endotoxins; D004280:Dobutamine