DECREASED LEFT-VENTRICULAR CONTRACTILITY DURING PORCINE ENDOTOXEMIA IS NOT PREVENTED BY IBUPROFEN

Objective: We investigated whether ibuprofen could prevent the early d ecrease in left ventricular contractility that occurs during porcine e ndotoxemia. Design: Prospective, randomized, controlled animal study. Setting: University research laboratory. Subjects: Adolescent crossbre d pigs (n = 28). Interventions: Anesthetized pigs were instrumented to measure hemodynamics and left ventricular pressures (using a Millar c atheter) and volumes (using a conductance catheter). Pigs were then tr eated in four groups, according to pretreatment using ibuprofen (15 mg /kg) or saline and subsequent treatment using endotoxin (0111:B4, 50 m u g/kg) or saline. Measurements and Main Results: Measurements of hemo dynamics and left ventricular pressures and volumes were repeated afte r pretreatment with ibuprofen (or saline in controls), and at hourly i ntervals for 4 hrs after the start of endotoxin or control saline infu sions. Left ventricular contractility was primarily assessed using the slope of the end-systolic pressure-volume relationship. Data were ana lyzed, using a repeated measures analysis of variance. The slope of th e end-systolic pressure-volume relationship was decreased at 4 hrs by 41 +/- 9% in the saline/endotoxin group (p < .05) and by 36 +/- 14% in the ibuprofen/endotoxin group (p < .05), so that ibuprofen pretreatme nt had no significant effect on the decrease in left ventricular contr actility. Mean arterial pressure decreased in the saline/endotoxin gro up by 23 +/- 12% at 1 hr (p < .05) and by 35 +/- 12% (p < .05) at 4 hr s. Ibuprofen significantly reduced the decrease in mean arterial press ure (2 +/- 6% increased at 1 hr, and 17 +/- 12% decreased at 4 hrs, bo th p < .05 compared with saline/endotoxin). Cardiac output increased b y 25% (p < .05) in the first hour, but then decreased to be slightly ( NS) below baseline at 4 hrs in both endotoxin groups. Mean pulmonary a rterial pressure was increased in the saline/endotoxin group by 154 +/ - 52% (p < .05) at 30 mins and by 118 +/- 40% (p < .05) at 4 hrs. Ibup rofen prevented the very acute increase in pulmonary arterial pressure (increased by 11 +/- 33% at 30 mins, p < .05 compared with saline/end otoxin) and significantly reduced the pulmonary hypertension at 4 hrs (increased by 70 +/- 25%, p < .05 compared with both baseline and sali ne/endotoxin). Conclusions: We conclude that products of the cyclooxyg enase pathway do not play a major role in the early decrease in left v entricular contractility after endotoxin. However, ibuprofen may have a role in reducing the other cardiovascular effects of sepsis.