Supplemental oxygen administration during mechanical ventilation reduces diaphragm blood flow and oxygen delivery

During mechanical ventilation (MV), supplemental oxygen (O₂) is commonly administered to critically ill patients to combat hypoxemia. Previous studies demonstrate that hyperoxia exacerbates MV-induced diaphragm oxidative stress and contractile dysfunction. Whereas normoxic MV (i.e., 21% O₂) diminishes diaphragm perfusion and O₂ delivery in the quiescent diaphragm, the effect of MV with 100% O₂ is unknown. We tested the hypothesis that MV supplemented with hyperoxic gas (100% O₂) would increase diaphragm vascular resistance and reduce diaphragmatic blood flow and O₂ delivery to a greater extent than MV alone. Female Sprague-Dawley rats (4-6 mo) were randomly divided into two groups: 1) MV + 100% O₂ followed by MV + 21% O₂ (n = 9) or 2) MV + 21% O₂ followed by MV + 100% O₂ (n = 10). Diaphragmatic blood flow (mL/min/100 g) and vascular resistance were determined, via fluorescent microspheres, during spontaneous breathing (SB), MV + 100% O₂, and MV + 21% O₂. Compared with SB, total diaphragm vascular resistance was increased, and blood flow was decreased with both MV + 100% O₂ and MV + 21% O₂ (all P < 0.05). Medial costal diaphragmatic blood flow was lower with MV + 100% O₂ (26 ± 6 mL/min/100 g) versus MV + 21% O₂ (51 ± 15 mL/min/100 g; P < 0.05). Second, the addition of 100% O₂ during normoxic MV exacerbated the MV-induced reductions in medial costal diaphragm perfusion (23 ± 7 vs. 51 ± 15 mL/min/100 g; P < 0.05) and O₂ delivery (3.4 ± 0.2 vs. 6.4 ± 0.3 mL O₂/min/100 g; P < 0.05). These data demonstrate that administration of supplemental 100% O₂ during MV increases diaphragm vascular resistance and diminishes perfusion and O₂ delivery to a significantly greater degree than normoxic MV. This suggests that prolonged bouts of MV (i.e., 6 h) with hyperoxia may accelerate MV-induced vascular dysfunction in the quiescent diaphragm and potentially exacerbate downstream contractile dysfunction.NEW & NOTEWORTHY This is the first study, to our knowledge, demonstrating that supplemental oxygen (i.e., 100% O₂) during mechanical ventilation (MV) augments the MV-induced reductions in diaphragmatic blood flow and O₂ delivery. The accelerated reduction in diaphragmatic blood flow with hyperoxic MV would be expected to potentiate MV-induced diaphragm vascular dysfunction and consequently, downstream contractile dysfunction. The data presented herein provide a putative mechanism for the exacerbated oxidative stress and diaphragm dysfunction reported with prolonged hyperoxic MV.