Nakanishi K, Tajima F, Osada H, Nakamura A, Yagura S, Kawai T, Suzuki M, Torikata C
Biochemical Division, Japan Air Self-Defense Force, Tachikawa, Japan.
Pathol Res Pract. 1996 Oct;192(10):1057-67. doi: 10.1016/S0344-0338(96)80049-5.
High altitude hypoxia is known to cause pulmonary hypertension in humans. Altitudes of 5500 m and 4000 m above sea level are considered to be the upper limits for short-term human survival and long-term human residence, respectively. To study the effects of hypobaric-hypoxic environments on pulmonary vascular beds, the physiologic and morphometric differences occurring in the pulmonary arteries of rats at the equivalent of these two altitude levels were compared. One hundred and ninety male rats were housed in a double-roomed mechanical chamber and subjected for 12 weeks to hypobaric-hypoxic environments equivalent to an altitude level of 5500 m or 4000 m. After 6-8 weeks, mean pulmonary arterial pressure (PAPm) was significantly higher in rats at the 5500 m level than in those at 4000 m. The external diameter of muscular arteries (M) and of partially muscular arteries (PM) in the lungs of rats at 8 and 12 weeks, and those of nonmuscular arteries (NM) around the alveolar sacs at 2 and 8 weeks were each significantly less in rats exposed to the 5500 m level than in those at 4000 m. At 4 weeks, the ratio of medial thickness to external diameter for M and PM around the alveolar ducts and alveolar sacs were greater in rats exposed to the 5500 m level than in those at 4000 m. Erythrocyte count, hemoglobin and hematocrit tests showed polycythemic patterns during the initial hypobaric period in both 5500 m-, and 4000 m-level rats. However, from 4 to 12 weeks, the hematologic values of the 4000 m-level rats declined progressively toward the upper end of the normal range. This study suggests (i) that elevated PAPm in rats exposed to hypobaric-hypoxic environments results from structural remodeling of all M, PM and NM within the lobule, and (ii) that an environment equivalent to the 5500 m level causes more severe pulmonary vascular changes than one equivalent to the 4000 m level. The hematologic results suggest that rats exposed to the equivalent of the upper limit for long-term human residence can acquire acclimatization, but not those exposed to the equivalent of the upper limit for short-term human survival.
众所周知，高原缺氧会导致人类患肺动脉高压。海拔5500米和4000米分别被认为是人类短期生存和长期居住的上限。为了研究低压低氧环境对肺血管床的影响，比较了在相当于这两个海拔水平的环境下，大鼠肺动脉出现的生理和形态学差异。190只雄性大鼠被饲养在一个双室机械舱中，在相当于海拔5500米或4000米的低压低氧环境中饲养12周。6 - 8周后，海拔5500米组大鼠的平均肺动脉压（PAPm）显著高于4000米组。在8周和12周时，暴露于海拔5500米环境的大鼠肺内肌性动脉（M）和部分肌性动脉（PM）的外径，以及在2周和8周时肺泡囊周围无肌性动脉（NM）的外径，均显著小于4000米组。在4周时，暴露于海拔5500米环境的大鼠肺泡管和肺泡囊周围M和PM的中膜厚度与外径之比大于4000米组。红细胞计数、血红蛋白和血细胞比容测试显示，在低压低氧初期，海拔5500米组和4000米组大鼠均出现红细胞增多模式。然而，从4周到12周，海拔4000米组大鼠的血液学值逐渐下降至正常范围上限。本研究表明：（i）暴露于低压低氧环境的大鼠PAPm升高是由于小叶内所有M、PM和NM的结构重塑所致；（ii）相当于海拔5500米的环境比相当于海拔4000米的环境引起更严重的肺血管变化。血液学结果表明，暴露于相当于人类长期居住上限环境的大鼠可以获得适应性，但暴露于相当于人类短期生存上限环境的大鼠则不能。
