Effects of aerosolized methylprednisolone on experimental neurogenic pulmonary injury.
We examined the effects of graded doses of methylprednisolone sodium succinate (MPSS)--0.05 (low), 0.5 (medium), and 5 mg/kg/hour (high)--on the development of neurogenic pulmonary injury in rabbits. The aerosolized drug was administered intratracheally for 5 hours beginning 10 minutes after a 2-minute elevation of the cerebrospinal fluid pressure (Pcsf) to 250 mm Hg. Compared to untreated control animals, the percentage of increase in pulmonary capillary permeability, as determined by 51Cr-labeled ethylenediaminetetraacetic acid clearance, was significantly less in the low and high dose MPSS groups. However, high dose MPSS was also associated with a significant decrease in compliance and increase in tissue hemorrhage (quantified by visual inspection). These results indicate biphasic effect of MPSS on alveolar capillary integrity after elevated Pcsf. The low dose minimized the extent of lung hemorrhage, pulmonary capillary leakage, and loss of lung compliance. In contrast, the high dose accelerated tissue hemorrhage and compliance loss, even though pulmonary capillary permeability was maintained near base line rates.
D000281:Administration, Intranasal; D000336:Aerosols; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D007427:Intracranial Pressure / Q000187:drug effects; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000494:pharmacology*; D011654:Pulmonary Edema / Q000188:drug therapy / Q000503:physiopathology*; D011817:Rabbits; D013997:Time Factors
D000336:Aerosols; D008775:Methylprednisolone