title: Systemic and regional hemodynamic effects of cyclo-oxygenase and thromboxane synthetase inhibition in normal and hyperdynamic endotoxemic rabbits.
abstract: We tested the hypothesis that prostaglandins (PGs) and thromboxane (Tx) A2 are important mediators of the hemodynamic derangements occurring in a rabbit model of hyperdynamic endotoxicosis. Rabbits were injected with either normal saline (NS) or Escherichia coli lipopolysaccharide (LPS; 1-3 micrograms/kg) and studied 6 hr later. Cardiac index (CI) and regional blood flow were determined using thermodilution and radioactive microspheres, respectively. Systemic and regional hemodynamics were determined before and 40 min after administering indomethacin (cyclo-oxygenase inhibitor; 5 mg/kg), UK38485 (Tx synthetase inhibitor; 10 mg/kg), or NS. LPS increased CI (P = .0024) and decreased mean arterial pressure (P = .0031) and systemic vascular resistance index (P = .0001). LPS increased flow to the heart and small intestine and decreased flow to the hepatic artery and pancreas. The systemic and regional hemodynamic effects of indomethacin were similar in NS- and LPS-treated rabbits. UK38485 decreased perfusion of skeletal muscle and diaphragm in both endotoxemic and control animals. This agent increased splenic perfusion only in NS-treated rabbits. Plasma levels of 6-keto PGF1 alpha (PGI2 metabolite) were typically undetectable in both NS- and LPS-treated rabbits. These data do not support the hypothesis that PG's or TxA2 are major determinants of the hemodynamic perturbations that occur in this endotoxicosis model.
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D016861:Cyclooxygenase Inhibitors; D004195:Disease Models, Animal; D004731:Endotoxins; D004926:Escherichia coli; D006439:Hemodynamics / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides; D008297:Male; D011453:Prostaglandins / Q000502:physiology*; D011817:Rabbits; D012772:Shock, Septic / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D013928:Thromboxane A2 / Q000502:physiology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
chemical_list: D016861:Cyclooxygenase Inhibitors; D004731:Endotoxins; D007093:Imidazoles; D008070:Lipopolysaccharides; D011453:Prostaglandins; C039242:dazmegrel; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; C044101:endotoxin, Escherichia coli; D013930:Thromboxane-A Synthase; D007213:Indomethacin