Dimethylthiourea ameliorates acute lung injury induced by phorbol myristate acetate in dogs.

BACKGROUND AND METHODS

The protective effects of dimethylthiourea, a potent scavenger of hydroxy radical (.OH) and hydrogen peroxide, in experimental lung injury in large animals remain controversial. The present study was designed to determine whether dimethylthiourea can ameliorate the acute lung injury produced in dogs by phorbol myristate acetate. Six dogs were infused with dimethylthiourea (0.75 g/kg in saline) for 1.5 hrs, beginning 1 hr before an i.v. bolus injection of phorbol myristate acetate (17 micrograms/kg); six dogs received phorbol myristate acetate (17 micrograms/kg) alone; and six dogs were infused with saline alone. Hemodynamic changes, arterial oxygenation, and the development of lung edema were monitored for 4 hrs after phorbol myristate acetate injection to assess the extent of lung damage.

RESULTS

As compared with the dogs that received phorbol myristate acetate alone, the edematous lung damage was significantly reduced in those dogs that received dimethylthiourea as well as phorbol myristate acetate. In the dimethylthiourea-treated dogs, the lung wet/dry weight ratios were smaller (p less than .01); protein concentrations in lung lavage fluid were lower (p less than .01); the decrease in PaO2 was significantly reduced (p less than .01); and there were significant reductions in the alveolar-arterial oxygen tension difference (P[A-a]O2) (p less than .01) and shunt (Qsp/Qt) (p less than .05). Also, dimethylthiourea significantly lowered the increased mean pulmonary arterial pressure levels during the second half of the experiment.

CONCLUSIONS

These experimental data suggest that dimethylthiourea is capable of reducing the neutrophil-mediated lung injury produced by the release of hydroxy radical and/or hydrogen peroxide in dogs exposed to phorbol myristate acetate.