Figure 2. Lactate/pyruvate ratios and nicotinate levels measured in simultaneously sampled arterial and internal jugular venous plasma, brain tissue concentration of NAD⁺ and Naprt mRNA expression, collected from Ndufs4^−/− and WT mice breathing air or after 4-weeks of 11% O₂.

Pearson correlation between arterial and internal jugular venous plasma lactate/pyruvate ratios in (A) Ndufs4^−/− (r=0.78, P=0.012) and WT (r=0.77, P=0.016) mice breathing air or in Ndufs4^−/− (r=0.98, P<0.0001) and WT (r=0.97, P=0.005) mice breathing 4-weeks of 11% O₂. (C) Volcano plot of the arterial-internal jugular venous (A-IJV) metabolite level difference depicting on the X-axis log₂fold-changes (log₂FC) and on the Y-axis statistical significance in Condition (Hypoxia vs. Normoxia) as -log₁₀ P-values in both Ndufs4^−/− and WT mice breathing 4-weeks of 11% O₂ (Hypoxia) compared to both Ndufs4^−/− and WT mice breathing air (Normoxia). Tissue concentration of NAD⁺ measured in the (D) brainstem, (E) cerebellum and (F) cerebrum. Tissue mRNA expression of Naprt measured in the (G) brainstem, (H) cerebellum and (I) cerebrum. Statistical significance was determined using two-way ANOVA with Sidak’s multiple comparisons test. All P-values generated from metabolic profiling were corrected for multiple hypothesis testing using the Benjamini-Hochberg procedure and false-discovery rate (FDR) <0.05 considered statistically significant. For Pearson correlation the ROUT method (Q = 0.5%) was used to identify and exclude 1 outlier [40]. n.s.= non-significant. Data are mean ± SD.