Lipopolysaccharide-induced myocardial depression is not mediated by cyclooxygenase products.
METHODS
We tested the hypothesis that a sublethal dose of lipopolysaccharide in vivo induces in vitro atrial depression in rats via release of cyclooxygenase products. Male Sprague-Dawley rats (mean weight 366 +/- 9 [SE] g) were injected iv at time 0 with Escherichia coli lipopolysaccharide (1 mg/kg, n = 22) or saline (2.5 mL, n = 11). Some animals injected with lipopolysaccharide were pretreated 30 mins before with ibuprofen (15 mg/kg, n = 7). At time 2 hrs, the hearts were harvested and the atria were immersed in tissue baths and attached to force displacement transducers. Blood was collected for measurement of thromboxane B2 (TxB2) by radioimmunoassay. Force of contraction and rate in response to four different preloads were measured. Afterward, the preload was changed to 1 g, and force of contraction and rate were evaluated in response to graded doses of isoproterenol.


RESULTS
Force of contraction was significantly (p less than .05) lower at all preloads in animals given lipopolysaccharide. Pretreatment with ibuprofen did not prevent the depression in force of contraction but prevented the increase in TxB2 seen after lipopolysaccharide injection (p less than .05). The force of contraction and rate response to isoproterenol were similar across groups.


CONCLUSIONS
These data suggest that cyclooxygenase products do not mediate lipopolysaccharide-induced cardiac dysfunction in the rat.
Heard
S O
SO
Department of Anesthesiology, University of Massachusetts Medical Center, Worcester 01655.
Baum
T D
TD
Feldman
H S
HS
Latka
C
C
Fink
M P
MP
D000818:Animals; D003864:Depression, Chemical; D004926:Escherichia coli; D007052:Ibuprofen / Q000494:pharmacology; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013928:Thromboxane A2 / Q000097:blood
D008070:Lipopolysaccharides; D013928:Thromboxane A2; D011451:Prostaglandin-Endoperoxide Synthases; D007052:Ibuprofen