Decreased left ventricular contractility during porcine endotoxemia is not prevented by ibuprofen

We investigated whether ibuprofen could prevent early decrease in left ventricular contractility that occurs during porcine endotoxemia.

Prospective, randomized, controlled animal study.

University research laboratory.

Adolescent crossbred pigs (n = 28).

Anesthetized 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 microg/kg) or saline.

Measurements 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 +/- 9% in the saline/endotoxin group (p < .05) and by 36 +/- 14% in the ibuprofen/endotoxin group (p < .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 +/- 12% at 1 hr (p < .05) and by 35 +/- 12% (p < .05) at 4 hrs. Ibuprofen significantly reduced the decrease in mean arterial pressure (2 +/- 6% increased at 1 hr, and 17 +/- 12% decreased at 4 hrs, both p<.05 compared with saline/endotoxin). Cardiac output increased by 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 arterial 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. Ibuprofen prevented the very acute increase in pulmonary arterial pressure (increased by 11 +/- 33% at 30 mins, p < .05 compared with saline/endotoxin) and significantly reduced the pulmonary hypertension at 4 hrs (increased by 70 +/- 25%, p < .05 compared with both baseline and saline/endotoxin).

We 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.