Endotoxin-induced myocardial depression in rats: effect of ibuprofen and SDZ 64-688, a platelet activating factor receptor antagonist.
We tested the hypothesis that lipopolysaccharide (LPS)-induced myocardial dysfunction is mediated by cyclooxygenase-derived metabolites of arachidonic acid or platelet activating factor (PAF). Ether-anesthetized rats were injected iv with normal saline (NS; 2.5 ml/kg), ibuprofen (cyclooxygenase inhibitor; 15 mg/kg), or SDZ 64-688 (PAF receptor antagonist; 5 mg/kg). Thirty minutes later, the rats were injected iv with NS (5 ml/kg) or Escherichia coli 0111:B4 LPS (20 mg/kg). Two hours later, atria were harvested, connected to an isometric force transducer-amplifier-recorder apparatus, and maintained in vitro in oxygenated 37.5 degrees C Krebs--Henseleit buffer. Force of contraction indexed to body weight (FOCI; g/kg) was significantly (P less than 0.05) lower in the NS/LPS group (N = 7) than in the NS/NS group (N = 7). Pretreatment with ibuprofen (ibuprofen/LPS group; N = 8) did not affect the adverse effect of LPS on atrial FOCI. In contrast, pretreatment with SDZ 64-688 (64-688/LPS group; N = 8) ameliorated (P less than 0.05) the deleterious effect of LPS on contractility. The PAF antagonist did not manifest intrinsic positive inotropic activity (64-688/NS group; N = 8). These results support the notion that LPS-induced myocardial dysfunction in the rat is mediated, at least in part, by PAF.
Baum
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TD
Department of Surgery, University of Massachusetts Medical Center, Worcester 01655.
Heard
S O
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Feldman
H S
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Latka
C A
CA
Fink
M P
MP
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001835:Body Weight; D003864:Depression, Chemical; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D006339:Heart Rate / Q000187:drug effects; D007052:Ibuprofen / Q000494:pharmacology*; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains
D004731:Endotoxins; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; C064759:SDZ 64-688; D015121:6-Ketoprostaglandin F1 alpha; D007052:Ibuprofen