OBJECTIVE: To test the hypothesis that recombinant Clara cell secretory protein (rhCC10) instillation would foster improved lung function, acute structural preservation, and attenuation of matrix metalloproteinase (MMP) activity in a surfactant-deficient, mechanically ventilated lung. DESIGN: Interventional laboratory study. SETTING: An academic medical research facility in the northeastern United States. SUBJECTS: Sedated, ventilated premature lambs. INTERVENTIONS: Preterm lambs (n = 18; 126 +/- 3 days gestation) were instrumented, ventilated, and treated with 100 mg/kg exogenous surfactant. Lambs were randomized to receive 0, 0.5, or 5.0 mg/kg rhCC10 (n = 6 per group) and were ventilated for 4 hrs. MEASUREMENTS AND MAIN RESULTS: Posttreatment, lung function and cardiopulmonary stability were monitored for the ventilation period and then animals were killed for in vitro surfactant function analysis, lung histomorphometry, and analysis of MMP-2, -7, and -9 as well as their tissue inhibitors (TIMP)-1 and -2. Ventilation efficiency and pulmonary compliance were improved in the 5.0-mg/kg rhCC10 group by 4 hrs. Lung expansion was variable in the apical regions only. MMP-2 quantity was greater in the apical than the base lung regions of rhCC10-treated groups, and rhCC10 decreased MMP-7 in the base of the lung. CONCLUSIONS: These data suggest that improved lung function in the surfactant-treated preterm lamb following intratracheal rhCC10 may be related to the reduction of proteolytic activity of MMP-7.
OBJECTIVE: To test the hypothesis that recombinant Clara cell secretory protein (rhCC10) instillation would foster improved lung function, acute structural preservation, and attenuation of matrix metalloproteinase (MMP) activity in a surfactant-deficient, mechanically ventilated lung. DESIGN: Interventional laboratory study. SETTING: An academic medical research facility in the northeastern United States. SUBJECTS: Sedated, ventilated premature lambs. INTERVENTIONS: Preterm lambs (n = 18; 126 +/- 3 days gestation) were instrumented, ventilated, and treated with 100 mg/kg exogenous surfactant. Lambs were randomized to receive 0, 0.5, or 5.0 mg/kg rhCC10 (n = 6 per group) and were ventilated for 4 hrs. MEASUREMENTS AND MAIN RESULTS: Posttreatment, lung function and cardiopulmonary stability were monitored for the ventilation period and then animals were killed for in vitro surfactant function analysis, lung histomorphometry, and analysis of MMP-2, -7, and -9 as well as their tissue inhibitors (TIMP)-1 and -2. Ventilation efficiency and pulmonary compliance were improved in the 5.0-mg/kg rhCC10 group by 4 hrs. Lung expansion was variable in the apical regions only. MMP-2 quantity was greater in the apical than the base lung regions of rhCC10-treated groups, and rhCC10 decreased MMP-7 in the base of the lung. CONCLUSIONS: These data suggest that improved lung function in the surfactant-treated preterm lamb following intratracheal rhCC10 may be related to the reduction of proteolytic activity of MMP-7.
Authors: Thomas L Miller; Lynn M Raab; Thomas H Shaffer; Alfred Schweikert; Frank Diana; Prem Fort; Alana S Frum; Joseph Pergolizzi; Robert B Raffa Journal: Cureus Date: 2022-09-07
Authors: Regina B Oakley; David G Tingay; Karen E McCall; Elizabeth J Perkins; Magdy Sourial; Peter A Dargaville; Prue M Pereira-Fantini Journal: Front Pediatr Date: 2019-08-21 Impact factor: 3.418