title: Inhibition of prostaglandin synthesis restores normal hemodynamics in canine hyperdynamic sepsis.
abstract: This study investigates the role of prostaglandins (PG) in hyperdynamic sepsis. Thirteen chronically instrumented dogs were rendered septic by implanting in the peritoneal cavity a fibrin clot containing viable Escherichia coli. One day later, cardiac output (CO) increased from 2.80 +/- 0.22 to 3.72 +/- 0.32 l/min (p = 0.011); heart rate (HR) increased from 122 +/- 8 to 147 +/- 6 beats/min (p = 0.005); mean pulmonary artery pressure (PAP) increased from 15 +/- 1 to 19 +/- 1 mmHg (p = 0.003); mean systemic arterial pressure (MAP) decreased from 120 +/- 5 to 107 +/- 7 mmHg; and systemic vascular resistance (SVR) decreased from 44.1 +/- 2.6 to 29.3 +/- 1.9 mmHg/l/min (p less than 0.001). Sixty minutes after intravenous injection of indomethacin (2 mg/kg) or ibuprofen (25 mg/kg), CO decreased to 2.60 +/- 0.21 l/min (p less than 0.001); HR decreased to 118 +/- 5 beats/min (p less than 0.001); PAP decreased to 17 +/- 1 mmHg (p = 0.021); and SVR increased to 43.7 mmHg/l/min (p less than 0.001). In seven control dogs, laparotomy alone did not significantly affect any of these parameters. Infusion of indomethacin caused a slight increase in MAP (106 +/- 4 to 116 +/- 4 mmHg, p = 0.035) but otherwise did not alter hemodynamics. It is concluded that administration of indomethacin or ibuprofen restores normal hemodynamics in a canine model of high-output sepsis, probably by inhibiting PG synthesis.
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D004927:Escherichia coli Infections / Q000503:physiopathology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010101:Oxygen Consumption; D010538:Peritonitis / Q000503:physiopathology; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis / Q000502:physiology; D018805:Sepsis / Q000503:physiopathology; D012772:Shock, Septic / Q000378:metabolism / Q000503:physiopathology*; D013928:Thromboxane A2 / Q000096:biosynthesis
chemical_list: D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D007052:Ibuprofen; D007213:Indomethacin