Table 2. Changes in respiratory parameters and blood gas analysis over time following lipopolysaccharide (LPS) administration.
| Elapsed time after LPS administration (min) |
FZP:Time | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 0 | 15 | 30 | 45 | 60 | 120 | 180 | 240 | P-value | ||
| PaO2 | Control♭ | 458 (5) | 577 (4) | 507 (4) | 337 (5) | 157 (5) | 377 (5) | 248 (4) | 210 (4) | |
| (mmHg) | [314–548] | [548–585] | [220–572] | [83–438] | [65–298] | [108–439] | [122–423] | [94–373] | ||
| Low-FZP♭ | 445 (5) | 573 (5) | 470 (5) | 455 (5) | 404 (5) | 351 (5) | 203 (4) | 145 (4) | 0.25 | |
| [285–509] | [538–584] | [231–567] | [135–525] | [84–451] | [99–430] | [53–331] | [50–250] | |||
| High-FZP♭ | 464 (5) | 538 (5)* | 523 (5) | 515 (5)* | 431 (5)* | 424 (5) | 331 (5) | 302 (4) | 0.88 | |
| [41–519] | [500–546] | [430–546] | [501–525] | [255–505] | [272–460] | [117–375] | [99–354] | |||
| pHa | Control♭ | 7.56 (5) | 7.54 (4) | 7.48 (4) | 7.42 (5) | 7.40 (5) | 7.45 (5) | 7.38 (4) | 7.32 (4) | |
| [7.49–7.57] | [7.49–7.58] | [7.43–7.56] | [7.28–7.50] | [7.23–7.46] | [7.32–7.51] | [7.19–7.46] | [7.05–7.45] | |||
| Low-FZP♭ | 7.54 (5) | 7.58 (5) | 7.51 (5) | 7.45 (5) | 7.43 (5) | 7.40 (5) | 7.36 (4) | 7.33 (4) | 0.73 | |
| [7.5–7.57] | [7.54–7.60] | [7.34–7.53] | [7.37–7.48] | [7.38–7.45] | [7.32–7.44] | [7.22–7.41] | [7.07–7.39] | |||
| High-FZP♭ | 7.55 (5) | 7.57 (5) | 7.52 (5) | 7.51 (5)* | 7.47 (5) | 7.43 (5) | 7.40 (5) | 7.34 (5) | 0.59 | |
| [7.53–7.57] | [7.54–7.58] | [7.42–7.53] | [7.49–7.52] | [7.44–7.49] | [7.37–7.50] | [7.32–7.44] | [7.28–7.41] | |||
| PaCO2 | Control | 40 (5) | 40 (4) | 38 (4) | 45 (5) | 47 (5) | 42 (5) | 42 (4) | 44 (4) | |
| (mmHg) | [36–47] | [35–47] | [33–43] | [35–51] | [40–60] | [35–57] | [32–72] | [34–82] | ||
| Low-FZP | 41 (5) | 38 (5) | 37 (5) | 40 (5) | 43 (5) | 43 (5) | 44 (4) | 46 (4) | 0.57 | |
| [39–47] | [33–41] | [34–51] | [33–48] | [36–53] | [40–53] | [39–69] | [36–79] | |||
| High-FZP | 39 (5) | 38 (5) | 37 (5) | 36 (5) | 39 (5)* | 40 (5) | 40 (5) | 43 (5) | 0.67 | |
| [36–42] | [34–48] | [36–44] | [35–39] | [37–41] | [36–46] | [38–46] | [36–46] | |||
| HCO3− | Control♭ | 35.6 (5) | 34.5 (5) | 27.1 (5) | 28.2 (5) | 28.5 (5) | 27.1 (5) | 24.6 (4) | 22.2 (4) | |
| (mEq/L) | [32.4–37.6] | [31.7–35.9] | [26.1–30.0] | [23.7–28.5] | [24.1–29.7] | [22.6–29.1] | [21.0–28.4] | [17.2–27.7] | ||
| Low-FZP♭ | 33.6 (5) | 34.5 (5) | 27.1 (5) | 25.4 (5) | 26.0 (5) | 26.6 (5) | 24.3 (4) | 22.2 (3) | 0.63 | |
| [33.1–37.4] | [31.6–35.3] | [23.4–30.4] | [23.7–31.3] | [25.0–31.1] | [23.7–30.4] | [23.5–27.6] | [21.2–23.6] | |||
| High-FZP♭ | 33.9 (5) | 33.8 (5) | 29.7 (5) | 28.2 (5) | 27.1 (5) | 26.5 (5) | 24.1 (5) | 22.4 (5) | 0.55 | |
| [31.9–35.5] | [31.3–34.5] | [28.4–30.8] | [28.0–29.4] | [26.8–28.9] | [25.7–29.2] | [23.2–26.3] | [19.7–24.3] | |||
| B.E. | Control♭ | 11.5 (5) | 11.7 (5) | 4.8 (5) | 4.2 (5) | 4.0 (5) | 3.7 (5) | -1.1 (4) | -4.8 (4) | |
| (mmol/L) | [10.1–14.1] | [8.4–13.4] | [2.9–8.1] | [3.0–4.7] | [3.1–4.1] | [2.1–5.0] | [-4.2–4.2] | [-10.1–3.8] | ||
| Low-FZP♭ | 11.0 (5) | 11.7 (5) | 4.9 (5) | 2.0 (5) | 2.0 (5) | 1.9 (5) | -0.8 (4) | -3.1 (3) | 0.99 | |
| [10.1–14.4] | [10.1–12.8] | [-0.7–7.9] | [0.3–6.7] | [1.2–5.8] | [-1.7–4.7] | [-1.1– -0.1] | [-8.3– -2.6] | |||
| High-FZP♭ | 11.0 (5) | 11.1 (5) | 7.0 (5) | 5.6 (5)* | 4.0 (5) | 3.3 (5) | -0.4 (5) | -1.3 (5) | 0.55 | |
| [9.4–12.8] | [8.6–11.9] | [4.1–7.8] | [5.5–6.3] | [3.2–5.4] | [1.0–6.3] | [-2.4–2.4] | [-6.3– -0.8] | |||
| Lactate | Control# | 1.2 (5) | 1.3 (5) | 2.8 (5) | 3.4 (5) | 3.5 (5) | 3.4 (5) | 4.9 (4) | 6.4 (4) | |
| (mmol/L) | [1.0–1.2] | [1.0–1.6] | [2.1–4.0] | [2.1–3.9] | [2.1–3.7] | [3.3–8.5] | [3.1–8.2] | [3.0–11.4] | ||
| Low-FZP# | 1.0 (5) | 1.2 (5) | 3.5 (5) | 3.8 (5) | 3.5 (5) | 3.4 (5) | 5.3 (4) | 6.2 (3) | 0.44 | |
| [0.8–1.2] | [0.8–1.7] | [2.7–4.5] | [3.1–3.9] | [2.8–3.9] | [3.0–5.0] | [3.6–6.4] | [3.9–10.0] | |||
| High-FZP# | 0.9 (5) | 1.2 (5) | 2.0 (5) | 2.4 (5) | 2.4 (5) | 2.9 (5) | 4.0 (5) | 4.6 (5) | 0.27 | |
| [0.6–1.1] | [0.9–1.3] | [1.3–4.0] | [1.7–4.8] | [2.1–4.6] | [2.4–4.2] | [3.6–6.2] | [3.9–7.9] | |||
| EVLW | Control | 283 (5) | 274 (5) | 297 (5) | 337 (5) | 315 (5) | 291 (5) | 330 (4) | 359 (4) | |
| (%) | [250–300] | [239–317] | [286–432] | [323–363] | [289–339] | [283–474] | [307–381] | [274–428] | ||
| Low-FZP | 374 (5) | 392 (5) | 378 (5) | 373 (5) | 354 (5) | 360 (5) | 399 (4) | 407 (3) | 0.82 | |
| [292–378] | [290–478] | [254–412] | [284–414] | [261–415] | [272–461] | [307–577] | [367–412] | |||
| High-FZP | 311 (5) | 309 (5) | 293 (5) | 345 (5) | 342 (5) | 312 (5) | 308 (5) | 352 (5) | 0.51 | |
| [282–338] | [293–339] | [284–354] | [289–406] | [285–384] | [288–368] | [287–433] | [315–466] | |||
| PVPI | Control# | 2.62 (5) | 2.45 (5) | 2.80 (5) | 3.78 (5) | 4.02 (5) | 3.83 (5) | 4.68 (4) | 4.91 (4) | |
| (%) | [1.80–2.80] | [2.00–2.77] | [1.80–3.88] | [2.50–4.50] | [2.50–4.38] | [2.20–6.40] | [2.65–4.97] | [2.08–6.40] | ||
| Low-FZP# | 2.73 (5) | 3.17 (5) | 2.95 (5) | 3.57 (5) | 3.67 (5) | 3.60 (5) | 4.61 (4) | 6.16 (3) | 0.72 | |
| [2.50–3.57] | [2.77–5.33] | [2.35–4.55] | [3.10–4.77] | [3.13–5.37] | [3.16–5.83] | [4.10–6.97] | [3.90–6.50] | |||
| High-FZP# | 3.03 (5) | 3.15 (5) | 3.03 (5) | 3.88 (5) | 4.30 (5) | 4.30 (5) | 4.73 (5) | 5.20 (5) | 0.64 | |
| [2.38–3.53] | [2.40–3.37] | [2.50–3.38] | [3.27–3.93] | [3.60–4.37] | [3.37–4.80] | [4.20–5.57] | [3.68–6.73] | |||
Values represent the median (number of pigs) [min–max]. Fuzapladib (FZP): Time: P-values indicate the P-values for the interaction between the dosage of fuzapladib and the elapsed time after LPS in a linear mixed-effects model. *: vs. control group (P<0.05), #: There was a significant increase in temporal changes within each group (P<0.05). ♭: There was a significant decrease in temporal changes within each group (P<0.05). PaO2: partial pressure of arterial oxygen, pHa: pH of arterial blood, PaCO2: partial pressure of arterial carbon dioxide, HCO3−: bicarbonate ion, B.E.: base excess, EVLW: extravascular lung water, PVPI: pulmonary vascular permeability index. For other complete blood cell count and biochemical test results, please refer to Supplementary File 3.