Measurement of oxygen free radicals in a rabbit shock lung model. Effect of superoxide dismutase and retinol.
OBJECTIVE
To develop an isolated rabbit lung model in which oxygen free radical activity could be measured and to examine the effects on the model of oxygen free radical scavengers.


METHODS
Prospective, randomized study.


METHODS
A clinical and basic research facility attached to a teaching hospital.


METHODS
Twenty-five New Zealand white rabbits weighing 3.5 to 4.5 kg.


METHODS
The mechanism of lung injury by oleic acid or by phorbol myristate acetate (20 ng/mL) plus polymorphonuclear neutrophils (PMA-PMN) in an ex vivo rabbit shock lung model may be the production of oxygen free radicals. Using a standard heart-lung preparation from these rabbits, baseline mean pulmonary artery pressure was maintained at 15 mm Hg and the mean airway pressure at 10 mm Hg. Experimental perfusates were infused over 30 minutes, followed by Krebs-Henseleit solution, pH 7.4. Dimethyl pyrroline oxide trapped oxygen free radicals, levels of which were measured by electron paramagnetic resonance spectroscopy. Lung injury was assessed by light and scanning electron microscopy and by lung weight.


RESULTS
A 5-fold increase in pulmonary artery pressure (P < .001) and a nearly 3-fold increase in mean airway pressure (P < .001) were observed in both the oleic acid and PMA-PMN models. Superoxide dismutase (20,000 U/kg), but not retinol palmitate (2000 U), prevented lung injury, the increases in pulmonary artery pressure and mean airway pressure, and the increase in oxygen free radicals in the PMA-PMN model. There were no increases in oxygen free radicals in the control, oleic acid, or PMA-PMN/superoxide dismutase groups (n = 5 in each group). Maximum mean +/- SD increases in oxygen free radicals were 112 +/- 22 nmol/L in the PMA-PMN group (P < .003, n = 5) and 108 +/- nmol/L in the PMA-PMN/retinol group (P < .003, n = 5).


CONCLUSIONS
The mechanism of lung injury in the PMA-PMN model is an increase in oxygen free radicals, because superoxide dismutase prevents both the rise in oxygen free radicals and lung injury. Administration of retinol does not prevent lung injury. Oleic acid produces injury not by an increase in oxygen free radicals but rather by another, unknown mechanism.
Tinsley
C H
CH
Department of Pediatrics, John A. Burns School of Medicine, University of Hawaii, Honolulu, USA.
Tinsley
L R
LR
Nishida
S D
SD
Premaratne
S
S
McNamara
J J
JJ
D000208:Acute Disease; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D004224:Diterpenes; D004578:Electron Spin Resonance Spectroscopy; D005069:Evaluation Studies as Topic; D016166:Free Radical Scavengers; D008168:Lung / Q000473:pathology / Q000648:ultrastructure; D008171:Lung Diseases / Q000473:pathology / Q000503:physiopathology*; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D011446:Prospective Studies; D011817:Rabbits; D011897:Random Allocation; D017382:Reactive Oxygen Species; D012128:Respiratory Distress Syndrome / Q000503:physiopathology; D000084562:Retinyl Esters; D012769:Shock / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000494:pharmacology; D014801:Vitamin A / Q000031:analogs & derivatives / Q000494:pharmacology
D016588:Anticarcinogenic Agents; D004224:Diterpenes; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D000084562:Retinyl Esters; D014801:Vitamin A; C014794:retinol palmitate; D013482:Superoxide Dismutase