BACKGROUND: Though natural surfactants (SF) are clinically superior to protein-free synthetic preparations, CHF-5633, a synthetic SF containing SP-B and SP-C analog peptides is a potential alternative to natural SF for treating neonatal respiratory distress syndrome (RDS). Nevertheless, information is lacking regarding the safety of this new treatment for the neonatal brain. We sought to compare the cerebral and pulmonary effects of this new synthetic surfactant (CHF5633) with those of natural porcine surfactant (Cursosurf) in premature lambs with RDS. METHODS: Twenty-one preterm lambs were randomly assigned to receive CHF5633, Curosurf, or no treatment (control). Pulmonary (gas exchange, lung mechanics) and cerebral (carotid artery blood flow, cerebral oxygen metabolism) effects were measured every 30 min for 6 h. Pulmonary and cerebral histological analysis were also performed. RESULTS: After delivery, lambs developed severe RDS (FIO2 :1, pH < 7.15, PaCO2 > 70 mmHg, PaO2 < 40 mmHg, Cdyn < 0.1 mL/cmH2 O/kg). By 30 min after treatment, animals in both SF-treated groups had consistently better gas exchange and lung mechanics than controls. After CHF5633 administration, PaCO2 , carotid artery blood flow, and cerebral oxygen delivery tended to slowly decrease compared to other groups. By 2 h, SF-treated groups had similar values of all parameters studied, these remaining steady for the rest of the experiment. Lambs administered CHF5633 obtained better lung and brain injury scores than controls. CONCLUSION: Intratracheal administration of a bolus of CHF5633 improves pulmonary status in preterm lambs with severe RDS, obtaining better lung and brain injury scores than controls and favorable cerebral hemodynamics, comparable to those with gold standard Curosurf treatment.
BACKGROUND: Though natural surfactants (SF) are clinically superior to protein-free synthetic preparations, CHF-5633, a synthetic SF containing SP-B and SP-C analog peptides is a potential alternative to natural SF for treating neonatal respiratory distress syndrome (RDS). Nevertheless, information is lacking regarding the safety of this new treatment for the neonatal brain. We sought to compare the cerebral and pulmonary effects of this new synthetic surfactant (CHF5633) with those of natural porcine surfactant (Cursosurf) in premature lambs with RDS. METHODS: Twenty-one preterm lambs were randomly assigned to receive CHF5633, Curosurf, or no treatment (control). Pulmonary (gas exchange, lung mechanics) and cerebral (carotid artery blood flow, cerebral oxygen metabolism) effects were measured every 30 min for 6 h. Pulmonary and cerebral histological analysis were also performed. RESULTS: After delivery, lambs developed severe RDS (FIO2 :1, pH < 7.15, PaCO2 > 70 mmHg, PaO2 < 40 mmHg, Cdyn < 0.1 mL/cmH2 O/kg). By 30 min after treatment, animals in both SF-treated groups had consistently better gas exchange and lung mechanics than controls. After CHF5633 administration, PaCO2 , carotid artery blood flow, and cerebral oxygen delivery tended to slowly decrease compared to other groups. By 2 h, SF-treated groups had similar values of all parameters studied, these remaining steady for the rest of the experiment. Lambs administered CHF5633 obtained better lung and brain injury scores than controls. CONCLUSION: Intratracheal administration of a bolus of CHF5633 improves pulmonary status in preterm lambs with severe RDS, obtaining better lung and brain injury scores than controls and favorable cerebral hemodynamics, comparable to those with gold standard Curosurf treatment.
Authors: David G Sweet; Mark A Turner; Zbyněk Straňák; Richard Plavka; Paul Clarke; Ben J Stenson; Dominique Singer; Rangmar Goelz; Laura Fabbri; Guido Varoli; Annalisa Piccinno; Debora Santoro; Christian P Speer Journal: Arch Dis Child Fetal Neonatal Ed Date: 2017-05-02 Impact factor: 5.747
Authors: Ann M Czyzewski; Lynda M McCaig; Michelle T Dohm; Lauren A Broering; Li-Juan Yao; Nathan J Brown; Maruti K Didwania; Jennifer S Lin; Jim F Lewis; Ruud Veldhuizen; Annelise E Barron Journal: Sci Rep Date: 2018-05-01 Impact factor: 4.379
Authors: Pavol Mikolka; Tore Curstedt; Riccardo Feinstein; Anders Larsson; Marian Grendar; Anna Rising; Jan Johansson Journal: Physiol Rep Date: 2021-01