Ibuprofen and methylprednisolone in a pig Pseudomonas ARDS model
Harvey, C.F.; Sugerman, H.J.; Tatum, J.L.; Sielaff, T.D.; Lee, E.C.; Blocher, C.R.
Circulatory Shock 21(3): 175-183
1987
ISSN/ISBN: 0092-6213 PMID: 3568279 Document Number: 298516
The effects of ibuprofen (I) and methylprednisolone (M) were studied in the Pseudomonas porcine model of adult respiratory distress syndrome (ARDS). Four groups of animals were anesthetized and ventilated with 0.5 FIO2, 5 cm PEEP, and 20 cc/kg tidal volume: a control group given saline alone; Pseudomonas infusion alone (P); Pseudomonas with ibuprofen (I), 12.5 mg/kg given at 20 and 120 min; and P with methylprednisolone (M), 30 mg/kg given at 20 and 120 min. We compared the alteration in pulmonary hemodynamics with the alteration in the plasma concentration of thromboxane (TxB2) and 6-keto PGF1.alpha. in the treated and untreated groups. Hemodynamic parameters measured included the pulmonary (PAP) and systemic (SAP) arterial pressures, cardiac index (Cl), thermal-cardiogreen extravascular lung water (EVLW), and PaO2. Albumin Flux was measured by a gamma scintrigraphic method (slope index; SI). P produced a dramatic increase in PAP (P < 0.05) with a progressive increase in EVLW and SI (P < 0.05) and fall (P < 0.05) in PaO2, CI, and SAP. The acute pulmonary hypertension was associated with a significant rise in TxB2 and 6-keto PGF1.alpha. in the Pseudomonas group. I effectively blocked the elevation of TxB2 and caused a significant but transient improvement in PAP and rise in PaO2. Albumin flux and water leak as measured by SI and ELVW were not affected by ibuprofen. M reduced the elevation of TxB2 and 6-keto PGF1.alpha. but failed to block these prostaglandins significantly. In conclusion, methylprednisolone significantly improved the cardiac index, but other hemodynamic changes and oxygenation were not significantly different from animals given Pseudomonas alone. These results were in marked contrast to those with ibuprofen, which produced significant improvements in arterial oxygenation and early pulmonary hypertension. Neither ibuprofen or methylprednisolone altered the increased pulmonary capillary permeability noted in this model.