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

During mechanical ventilation (MV), supplemental oxygen (O) 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% O) diminishes diaphragm perfusion and O delivery in the quiescent diaphragm, the effect of MV with 100% O is unknown. We tested the hypothesis that MV supplemented with hyperoxic gas (100% O) would increase diaphragm vascular resistance and reduce diaphragmatic blood flow and O delivery to a greater extent than MV alone. Female Sprague-Dawley rats (4-6 mo) were randomly divided into two groups: ) MV + 100% O followed by MV + 21% O ( = 9) or ) MV + 21% O followed by MV + 100% O ( = 10). Diaphragmatic blood flow (mL/min/100 g) and vascular resistance were determined, via fluorescent microspheres, during spontaneous breathing (SB), MV + 100% O, and MV + 21% O. Compared with SB, total diaphragm vascular resistance was increased, and blood flow was decreased with both MV + 100% O and MV + 21% O (all < 0.05). Medial costal diaphragmatic blood flow was lower with MV + 100% O (26 ± 6 mL/min/100 g) versus MV + 21% O (51 ± 15 mL/min/100 g; < 0.05). Second, the addition of 100% O during normoxic MV exacerbated the MV-induced reductions in medial costal diaphragm perfusion (23 ± 7 vs. 51 ± 15 mL/min/100 g; < 0.05) and O delivery (3.4 ± 0.2 vs. 6.4 ± 0.3 mL O/min/100 g; < 0.05). These data demonstrate that administration of supplemental 100% O during MV increases diaphragm vascular resistance and diminishes perfusion and O 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. This is the first study, to our knowledge, demonstrating that supplemental oxygen (i.e., 100% O) during mechanical ventilation (MV) augments the MV-induced reductions in diaphragmatic blood flow and O 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.