Abstract 2073 Pulmonary: General Lung Biology Poster Symposium, Sunday, 5/2

Nitric oxide (NO) has been successfully applied in patients with a variety of pulmonary disorders. Although the therapeutic benefits of NO may be substantial, potential pulmonary toxicity has been suggested based on oxidant production. However, other studies suggest that NO may produce less pulmonary toxicity than hyperoxia. We hypothesized that the pulmonary toxicity from inhaled NO, assessed by evidence of lung inflammation and airway dysfunction, is less than hyperoxia-induced lung damage. Newborn guinea pigs (GPs) which are highly susceptible to lung damage induced by hyperoxia exposure due to their inability to increase lung antioxidant enzymes were exposed to room air (RA), 95% oxygen (O2), or 20 ppm of NO for up to 5 days. Pressure volume (PV) curves were obtained. Airway rings segments were used to produce comparative cumulative dose responses to acetylcholine (ACh). In bronchoalveolar lavage (BAL) samples, chymotryptic, elastolytic, and tryptic activity was detected by colorimetric assay and total protein was determined by Bradford assay. NO levels were measured by a NO analyzer (Sievers 280). Hyperoxia exposed GPs had poor weight gain and developed symptoms of respiratory distress by 3-5 days while NO and RA exposed GPs did not. Hyperoxia exposed GPs had reduced lung volumes at 35 cm H2O pressure (O2, 33.1 ml/kg; NO & RA, 48 ml/kg; p<0.04). The NO exposed GPs had less airway contractility to ACh (NO vs O2, p<0.01). Hyperoxia exposed GPs BAL showed increased proteinase activity [Δ/18 hr (chymotryptic, O2, 689.2 mOD vs RA, 113.8 mOD and NO, 118 mOD, p<0.05; tryptic, O2, 199.2 mOD vs RA, 63.3 mOD and NO, 60.8 mOD, p<0.05; elastolytic, O2, 45.6 mOD vs NO, 8.8 mOD, p<0.05)]. There was no difference in proteinase activity of NO vs RA exposed GPs (p>0.05). Hyperoxia exposed GPs BAL showed increased total protein (O2, 3.3 mg/ml vs NO, 0.1 mg/ml; p<0.05). Histopathologic comparisons are pending. Hyperoxia exposed GPs had increased NO levels in BAL compared to RA (O2, 12.8 uM vs RA, 3.5 uM; p<0.05) while NO exposed GPs had values of 4.2 uM. Summary: In contrast to hyperoxia exposed newborn GPs, NO exposed GPs demonstrated no evidence of pulmonary toxicity and dysfunction based on: 1. No clinical signs and symptoms of respiratory distress, 2. No reduction of pulmonary compliance, 3. No increase in airway contractility, 4. No increase in pulmonary proteinase activity, and 5. No increase in pulmonary protein amount. These results suggest that there is less pulmonary toxicity in animals exposed to 20 ppm of NO for 5 days than lung damage induced by exposure to 95% oxygen.