Original articleSphingosine 1-phosphate rescues canine LPS-induced acute lung injury and alters systemic inflammatory cytokine production in vivo
Section snippets
Methods
Animal protocols were approved by the University of Pittsburgh and the Johns Hopkins University Institutional Animal Care and Use Committees.
Experimental groups
Eighteen 1-year-old male beagles (10–15 kg) received intrabronchial instillation of LPS (2–4 mg/kg) under direct bronchoscopic visualization. The animals then received either iv S1P (85 μg/kg) or vehicle (saline) 1 h after LPS instillation (n, 9 each group).
Intrabronchial LPS induces severe lung injury in vehicle-treated animals
In the 9 animals who received intrabronchial LPS followed by vehicle, PaO2/FiO2 declined throughout the duration of the experiment (from 561.0 ± 15.3 to 294.0 ± 31.3; Table I). Qs/Qt increased rapidly and progressively throughout the
Discussion
Using a translationally relevant large animal model of inflammatory ALI, we recently demonstrated that iv S1P (85 μg/kg) administered concomitantly with intratracheal LPS reduced shunt formation, attenuated alveolar protein accumulation, and decreased regional alveolar edema formation in beagles compared with animals injured with LPS alone.17 The current study has extended these findings to demonstrate that iv S1P reduces physiologic lung injury when administered subsequent to injury induction
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Supported by grants from the NHLBI F32 HL74569, P50 HL073994, P01 HL 58604, and K08 HL083101.