Optimal inhaled oxygen and carbon dioxide concentrations for post-cardiac arrest cerebral reoxygenation and neurological recovery

Figures

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  Figure 1. Study procedures and measurements at baseline, asphyxia, cardiac arrest, cardiopulmonary resuscitation, and reperfusion ABG, arterial blood gas; CA, cardiac arrest; CBF, cerebral blood flow; CPR, cardiopulmonary resuscitation; ECG, electrocardiogram; EtCO2, partial pressure of end-tidal carbon dioxide; HR, heart rate; MAP, mean arterial pressure; ROSC, return of spontaneous circulation.

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  Figure 2. Brain oxygenation during invasive monitoring (A), (C), and (E) Trends of CBF and PbtO2 after administration of different combinations of iO2 and iCO2. (B), (D), and (F) Levels of CBF and PbtO2 at the end of the intervention, 150 min post-ROSC. Black: 50% iO2 group; pink: 88% iO2 group; green: 50% iO2 + 12% iCO2 group; purple: 88% iO2 + 12% iCO2 group. The administration of 12% iCO2 increased CBF and PbtO2. Data are presented as the median with an interquartile range or a boxplot. Pairwise comparisons of physiological parameters between experimental groups were performed by post hoc Dunn’s test. CA, cardiac arrest; CBF, cerebral blood flow; ΔPbtO2, delta of partial pressure of brain tissue oxygenation; iCO2, inhaled carbon dioxide; iO2, inhaled oxygen; KW: Kruskal-Wallis; ROSC, return of spontaneous circulation.

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  Figure 3. Survival curves and neurological outcomes at 24 h post-ROSC (A) Kaplan-Meier survival curves. (B) Neurological function scores at 24 h post-ROSC. Black: 50% iO2 group; pink: 88% iO2 group; green: 50% iO2 + 12% iCO2 group; purple: 88% iO2 + 12% iCO2 group. The neurological function score is presented as a boxplot. Pairwise comparisons between experimental groups were performed using post hoc Dunn’s test. There were no significant differences in survival among experimental groups. The neurological function score was higher in groups with 12% iCO2 than in groups without it. iCO2, inhaled carbon dioxide; iO2, inhaled oxygen; KW, Kruskal-Wallis; ROSC, return of spontaneous circulation.

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  Figure 4. ELISA and TBARS assay at 24 h post-ROSC (A) NSE levels. (B) S100β levels. (C) MDA: levels. (D) Cardiac troponin I levels. Black: 50% iO2 group; pink: 88% iO2 group; green: 50% iO2 + 12% iCO2 group; purple: 88% iO2 + 12% iCO2 group. The neuronal injuries were evaluated using the NSE and S100β plasma concentrations. Oxidative injury was assessed using the MDA level in the hippocampus. Data are presented as a boxplot. Pairwise comparisons between experimental groups were performed using post hoc Dunn’s test. ELISA, enzyme-linked immunosorbent assay; iCO2, inhaled carbon dioxide; iO2, inhaled oxygen; KW: Kruskal-Wallis; MDA, malondialdehyde; NSE, neuron-specific enolase; ROSC, return of spontaneous circulation; TBARS, thiobarbituric acid reactive substance.

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  Figure 5. TUNEL assay and FJC staining at 24 h post-ROSC (A) TUNEL assay of the hippocampus. (B and C): Quantitative analysis of TUNEL assay for CA1 and CA3 regions, respectively. (D) FJC staining of the hippocampus. (E and F) Quantitative analysis of FJC staining for CA1 and CA3 regions, respectively. Black: 50% iO2 group; pink: 88% iO2 group; green: 50% iO2 + 12% iCO2 group; purple: 88% iO2 + 12% iCO2 group. Neuronal degeneration was evaluated by FJC staining. The hippocampal TUNEL-positive or FJC-positive cell density was used to quantify the level of apoptosis or neuronal degeneration, respectively. The coronal brain sections were subjected to TUNEL (green), FJC (green), and DAPI (bluish-violet) staining. Fluorescence microscopy was used to image hippocampal CA1 and CA3 regions at 50× magnification. Red rectangles indicate CA1 and CA3 regions selected for quantification. The scale bar represents 1000 μm. Samples were randomly selected for TUNEL assay or FJC staining. Data are presented as a boxplot. Pairwise comparisons between experimental groups were performed using post hoc Dunn’s test. DAPI, 4′,6-diamidino-2-phenylindole; FJC, Fluoro-Jade C; iCO2, inhaled carbon dioxide; iO2,…