Orthopedic trauma-induced pulmonary injury in the obese Zucker rat

Abstract

Objective: Obese subjects with orthopedic trauma exhibit increased inflammation and an increased risk of pulmonary edema. Prostaglandin E(2) (PGE(2) ) production is elevated during inflammation and associated with increased vascular permeability. We hypothesize that pulmonary edema in obesity following orthopedic trauma is due to elevated PGE(2) and resultant increases in pulmonary permeability.

Methods: Orthopedic trauma was induced in both hindlimbs in lean (LZ) and obese Zucker rats (OZ). On the following day, plasma interleukin-6 (IL-6) and PGE(2) levels, pulmonary edema, and pulmonary gas exchange capability were compared between groups: LZ, OZ, LZ with trauma (LZT), and OZ with trauma (OZT). Vascular permeability in isolated lungs was measured in LZ and OZ before and after application of PGE(2) .

Results: As compared with the other groups, the OZT exhibited elevated plasma IL-6 and PGE(2) levels, increased lung wet/dry weight ratio and bronchoalveolar protein concentration, and an impaired pulmonary gas exchange. Indomethacin treatment normalized plasma PGE(2) levels and pulmonary edema. Basal pulmonary permeability in isolated lungs was higher in OZ than LZ, with a further increase in permeability following treatment with PGE(2) .

Conclusions: These results suggest that pulmonary edema in OZ following orthopedic trauma is due to an elevated PGE(2) and resultant increases in pulmonary permeability.

Figure 1

1a and 1b represents the plasma IL-6 and PGE₂ levels in each animal group, respectively. OZ exhibited higher basal levels of circulating IL-6 as compared with the LZ. Orthopedic trauma further increased the IL-6 levels in OZ with no effect in the LZ (* P < 0.05 vs. lean; + P < 0.05 vs. control within obese; n = 5 for each group). OZT exhibited a significant higher PGE₂ levels as compared with the other groups (+ P < 0.01 OZT vs. the other groups; n = 6 for LZ, n = 4 for OZ, n = 5 for LZT, OZT and OZT + indomethacin).

Figure 2

2a and 2b represents the bronchoalveolar protein concentrations and the ratio of wet and dry lung weight, respectively. The bronchoalveolar protein concentrations (*P < 0.05 vs. OZ; n = 4 for each groups) or the wet and dry lung weight ratio (*P < 0.05 vs. OZ; n = 10 for each group) were similar between LZ, OZ, and LZT but were significantly increased in the OZT.

Figure 3

a shows that the basal capillary permeability is significantly higher in the OZ as compared with LZ, with orthopedic trauma altering the permeability in neither LZT nor OZT. Treatment with PGE₂ increased the vascular permeability (Figure 3a) without altering the resistance in both LZ and OZ (Figure 3b) (* P < 0.05 PGE₂ vs. control or trauma; + P < 0.01 lean vs. obese; n = 5 for the all lean and obese within control and lean within trauma; n = 4 for lean and obese within PGE₂ and obese with trauma).

Figure 4

a shows that breathing 100% O₂ resulted a blunted vasoconstriction in OZT, with treatment with indomethacin normalizing the vasoconstrictor response (* P < 0.01 vs. all the other groups; n = 8 for LZ; n = 5 for the other groups). Figure 4b shows that increasing [O₂] in the PSS resulted in similar vasoconstrictor responses between groups (n = 5 for each group).