Postlethwait E M, Langford S D, Bidani A
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555-0876.
Toxicol Appl Pharmacol. 1994 Mar;125(1):77-89. doi: 10.1006/taap.1994.1051.
Using an isolated rat lung model, we investigated the characteristics of pulmonary O3 absorption, including the contributory role of chemical reaction vs physical solubility. Due to the physicochemical similarities between O3 and NO2, we utilized investigational strategies analogous to those previously employed to characterize NO2 absorption kinetics. The effects of vascular perfusion, temperature, inspired concentration ([O3]i), surface area, and minute ventilation (tidal volume (Vt) times ventilation frequency (f)) on air space O3 clearance during quasi-steady-state exposures were investigated using fractional uptakes (%U) and reactive uptake coefficients (k') as endpoints. We found the following: (1) At 1 ppm [O3]i (37 degrees C), %U (95 +/- 5%) was perfusion independent (60 min). (2) %U displayed temperature dependence (r = 0.99). Activation energies (Ea) and Q10 were computed from Arrhenius plots (ln k' vs 1/T; r = -0.99). For 1 ppm (11-37 degrees C), Ea = 4140 kcal/g.mol and Q10 = 1.23. (3) Absorption demonstrated [O3]i dependence. At 25 degrees C, < or = 1 ppm displayed %U = 86 +/- 4% with k' = 234 ml/min. Exposures > 1 ppm resulted in decreasing %U and k' (5 ppm %U = 60 +/- 3% and k' = 121 ml/min). (4) To evaluate epithelial damage, lactate dehydrogenase (LDH) activity was quantified in cell-free bronchoalveolar lavage fluid. For exposures < or = 1 ppm LDH equaled control, while for exposures > 1 ppm LDH steadily increased to a four-fold maximum at 5 ppm. (5) O3 uptake was independent of functional residual capacity-induced changes in air space surface area. (6) Absorption was proportional to Vt (r = 0.99) and displayed notable ventilation frequency-dependent decline above 70 breaths per minute. Based on the perfusion independence, temperature dependence, and the Ea and Q10, we conclude that O3 absorption in isolated lungs involves a reactive component. While k' remained stable from 0 to 1 ppm O3, at concentrations above 1 ppm other contributory factors such as O3/substrate reaction kinetics, epithelial damage, and solute O3 backpressure may affect the overall net absorption rate. In addition, the data suggest that O3 uptake may be principally localized to the conducting airways.
我们使用离体大鼠肺模型，研究了肺对臭氧（O₃）吸收的特性，包括化学反应与物理溶解度的贡献作用。由于O₃与二氧化氮（NO₂）在物理化学性质上相似，我们采用了类似于先前用于表征NO₂吸收动力学的研究策略。以分数摄取率（%U）和反应摄取系数（k'）为指标，研究了在准稳态暴露期间血管灌注、温度、吸入浓度（[O₃]i）、表面积和分钟通气量（潮气量（Vt）乘以通气频率（f））对气腔O₃清除率的影响。我们发现：（1）在37℃、[O₃]i为1 ppm时，%U（95±5%）与灌注无关（60分钟）。（2）%U表现出温度依赖性（r = 0.99）。根据阿伦尼乌斯图（ln k'对1/T；r = -0.99）计算活化能（Ea）和Q₁₀。对于1 ppm（11 - 37℃），Ea = 4140千卡/克·摩尔，Q₁₀ = 1.23。（3）吸收表现出[O₃]i依赖性。在25℃时，≤1 ppm时%U = 86±4%，k' = 234毫升/分钟。暴露于>1 ppm时，%U和k'降低（5 ppm时%U = 60±3%，k' = 121毫升/分钟）。（4）为评估上皮损伤，对无细胞支气管肺泡灌洗液中的乳酸脱氢酶（LDH）活性进行了定量分析。暴露于≤1 ppm时LDH与对照组相当，而暴露于>1 ppm时，LDH在5 ppm时稳定增加至最大值的四倍。（5）O₃摄取与功能残气量引起的气腔表面积变化无关。（6）吸收与Vt成正比（r = 0.99），且在每分钟呼吸频率高于70次时表现出明显的通气频率依赖性下降。基于灌注独立性、温度依赖性以及Ea和Q₁₀，我们得出结论，离体肺中O₃的吸收涉及一个反应性成分。虽然在O₃浓度从0到1 ppm时k'保持稳定，但在浓度高于1 ppm时，其他影响因素如O₃/底物反应动力学、上皮损伤和溶质O₃背压可能会影响整体净吸收率。此外，数据表明O₃摄取可能主要局限于传导气道。
