Journal of Applied Physiology, Vol 59, Issue 5 1464-1471, Copyright © 1985 by American Physiological Society
Effects of flunixin meglumine on cardiopulmonary responses to endotoxin in ponies
N. C. Olson, R. E. Meyer and D. L. Anderson
The effects of endotoxemia on cardiopulmonary parameters, before and after
cyclooxygenase blockade, were determined in anesthetized ponies
spontaneously breathing a mixture of halothane and 100% O2. Escherichia
coli endotoxin was infused intravenously at 20 micrograms/kg for 1 h
followed by 10 micrograms X kg-1 X h-1 the subsequent 4 h. By 15 min
endotoxin increased mean pulmonary arterial pressure (Ppa), pulmonary
vascular resistance (PVR), and alveolar dead space ventilation (VDA/VT),
and these were followed by a return to base-line values by 30 min. A second
increase in PVR occurred by 5 h of endotoxemia. The early increases in Ppa,
PVR, and VDA/VT were blocked by flunixin meglumine (FM), a cyclooxygenase
inhibitor. Endotoxin decreased central plasma volume by 1 h and cardiac
index by 3 h; hematocrit and plasma protein concentration were increased by
0.5 and 1.5 h, respectively, indicating a loss of plasma volume. These
changes were also blocked or attenuated by FM. Moreover, in ponies treated
with endotoxin + FM, cardiac index increased, indicating the presence of a
cardiac-stimulating factor. We conclude that endotoxemia in ponies causes
cardiopulmonary dysfunction that is mediated by cyclooxygenase-dependent
and possibly cyclooxygenase-independent metabolites.
