Table 1.

Summary of animal model studies for hypoxia-HYPEROXIA fluctuation (Cycling)

Reference	Organism	Cycling conditions		Cycling effect
		hypoxia	Hyperoxia
Ratner et al.19	Mouse, start at P3	8% O2 (N2 balanced)	65% O2	• Fewer alveoli compared to HYPEROXIA
		10 min/episode*	All other times when not in episode	• Decreased pulmonary total/oxidized glutathione ratio (anti- oxidative capacity)
		1 episode/day for 1 Wk.+		• Elevation of protein carbonyl content (protein oxidation)
		1 episode/2days for 1 Wk.
		*monitor SO2 by pulse oximetry
		Total 4 Weeks
Schmiedl et al.81	Mouse, start with pregnant mothers E14	10% O2	75% O2	• Higher volume of the parenchymal airspaces
		Pregnant mice	Pups	• Higher wall thickness of septa (not significant)
		E14->E18	P1->P14	• Lower volume of lamellar bodies in alveolar epithelial cells type II (by EM)
Valencia et al.82	Rat, start at P0	12% O2	50% O2	• At P23 and P45, compared with normoxia:
		1 min/episode	All other time	∘ Intermittent hypoxia decreased pO2
		3 episodes/cluster, 10 min apart		∘ HYPEROXIA increased pO2
		8 clusters/day for 2 Wks.		∘ No significant difference in SaO2 in the HYPEROXIA group
		Total 2 Weeks (P0->P14)
Chang et al.84	Rat, start at P0 (within 5hr of birth)	12% O2	50% O2	• No HYPEROXIA only group was done
		2 min/episode	All other time	• No histology
		3 episodes/cluster, 10 min apart		• Measured VEGF, MMP2,9, TIMP by immunoassays and reversal of the effects by SOD mimetic
		4 clusters/day (every 6hr) for 2 Wks.
		Total 2 Weeks (P0->P14)
Sucre et al.83	3D organoid human fetal lung fibroblasts	10% O2	70% O2	• Markers of fibroblast activation were increased vs normoxia
		24 hr. then HYPEROXIA	24 hr. then hypoxia	• No comparison to hyperoxia alone made
		Total 4 days