Regional blood flow distribution in endotoxin-treated dogs: modification by ibuprofen.
OBJECTIVE
The aim of this study was to determine whether the improved hemodynamic profiles reported with cyclooxygenase inhibition during sepsis include improvements in tissue perfusion is unknown. Our hypothesis was that cyclooxygenase inhibition with ibuprofen will prevent the endotoxin-induced alterations in regional blood flow distribution from developing and/or restore the endotoxin-induced loss of responsiveness to intravascular volume expansion.


METHODS
We measured cardiac output, regional blood flow, and total systemic shunt flow in dogs using radiolabeled 15-microns microspheres. These parameters were assessed in control (N = 10) and endotoxin-treated animals (N = 7). Additional endotoxin-treated animals (N = 7) were also pretreated with ibuprofen.


RESULTS
Compared with controls, endotoxin-treated animals exhibited marked reductions in blood flow to most systemic organs that were not reversed with large, intravenous saline infusions (ie, isotonic saline; 40 mL/kg; N = 4). By contrast, although ibuprofen pretreatment (12.5 mg/kg; N = 7) completely prevented the reductions in mean arterial pressure caused by endotoxin from occurring, it did little to prevent the development of endotoxin-induced alterations in regional blood flow distribution. Nonetheless, in contrast to the endotoxin-treated animals, there were significant increases in cardiac output and blood flow to several organs after saline infusion in the ibuprofen-pretreated animals.


CONCLUSIONS
Cyclooxygenase inhibition with ibuprofen has few direct effects on regional blood flow distribution after endotoxin. However, cyclooxygenase inhibition with ibuprofen does attenuate the endotoxin-induced decrease in vascular responsiveness to intravenous saline infusion.
Winslow
C
C
Department of Medicine, Ohio State University, Columbus 43210.
Dorinsky
P M
PM
D000818:Animals; D001784:Blood Gas Analysis; D004285:Dogs; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli; D005440:Fluid Therapy; D006439:Hemodynamics / Q000187:drug effects*; D007052:Ibuprofen / Q000494:pharmacology*; D008863:Microspheres; D011865:Radioisotope Dilution Technique; D012039:Regional Blood Flow / Q000187:drug effects; D018805:Sepsis / Q000503:physiopathology* / Q000628:therapy
D004731:Endotoxins; D007052:Ibuprofen