ObjectiveWe investigated whether ibuprofen could prevent the early decrease in left ventricular contractility that occurs during porcine endotoxemia.DesignProspective, randomized, controlled animal study.SettingUniversity research laboratory.SubjectsAdolescent crossbred pigs (n equals 28).InterventionsAnesthetized pigs were instrumented to measure hemodynamics and left ventricular pressures (using a Millar catheter) and volumes (using a conductance catheter). Pigs were then treated in four groups, according to pretreatment using ibuprofen (15 mg/kg) or saline and subsequent treatment using endotoxin (0111:B4, 50 micro gram/kg) or saline.Measurements and Main ResultsMeasurements of hemodynamics and left ventricular pressures and volumes were repeated after pretreatment with ibuprofen (or saline in controls), and at hourly intervals for 4 hrs after the start of endotoxin or control saline infusions. Left ventricular contractility was primarily assessed using the slope of the end-systolic pressure-volume relationship. Data were analyzed, using a repeated-measures analysis of variance. The slope of the end-systolic pressure-volume relationship was decreased at 4 hrs by 41 plus minus 9% in the saline/endotoxin group (p less than .05) and by 36 plus minus 14% in the ibuprofen/endotoxin group (p less than .05), so that ibuprofen pretreatment had no significant effect on the decrease in left ventricular contractility. Mean arterial pressure decreased in the saline/endotoxin group by 23 plus minus 12% at 1 hr (p less than .05) and by 35 plus minus 12% (p less than .05) at 4 hrs. Ibuprofen significantly reduced the decrease in mean arterial pressure (2 plus minus 6% increased at 1 hr, and 17 plus minus 12% decreased at 4 hrs, both p less than .05 compared with saline/endotoxin). Cardiac output increased by 25% (p less than .05) in the first hour, but then decreased to be slightly (NS) below baseline at 4 hrs in both endotoxin groups. Mean pulmonary arterial pressure was increased in the saline/endotoxin group by 154 plus minus 52% (p less than .05) at 30 mins and by 118 plus minus 40% (p less than .05) at 4 hrs. Ibuprofen prevented the very acute increase in pulmonary arterial pressure (increased by 11 plus minus 33% at 30 mins, p less than .05 compared with saline/endotoxin) and significantly reduced the pulmonary hypertension at 4 hrs (increased by 70 plus minus 25%, p less than .05 compared with both baseline and saline/endotoxin).ConclusionsWe conclude that products of the cyclooxygenase pathway do not play a major role in the early decrease in left ventricular contractility after endotoxin. However, ibuprofen may have a role in reducing the other cardiovascular effects of sepsis.(Crit Care Med 1996; 24:815-819)