Ibuprofen and methylprednisolone in a pig Pseudomonas ARDS model.
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 (C1), thermal-cardiogreen extravascular lung water (EVLW), and PaO2. Albumin Flux was measured by a gamma scintigraphic method (slope index; SI). P produced a dramatic increase in PAP (P less than 0.05) with a progressive increase in EVLW and SI (P less than 0.05) and fall (P less than 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 EVLW were not affected by ibuprofen. M reduced the elevation of TxB2 and 6-keto PGF1 alpha but failed to block these prostaglandins significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects; D007052:Ibuprofen / Q000627:therapeutic use*; D008775:Methylprednisolone / Q000627:therapeutic use*; D011552:Pseudomonas Infections / Q000188:drug therapy*; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D013552:Swine; D013929:Thromboxane B2 / Q000097:blood
D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D007052:Ibuprofen; D008775:Methylprednisolone