Smith R A, Venus B, Mathru M, Shirakawa Y
Crit Care Med. 1984 Jul;12(7):576-8. doi: 10.1097/00003246-198407000-00006.
Acute alveolar injury induced by subcutaneous injection of N-nitroso-N-methylurethane (NNNMU) closely resembles the pathology of human adult respiratory distress syndrome (ARDS). However, its effects on cardiovascular function have not been evaluated. We measured hemodynamic variables and venous admixture (Qsp/Qt at FIO2 0.21) and shunt fraction (Qsp/Qt at FIO2 1.0) in 7 dogs. The measurements were repeated when a single subcutaneous injection of 8.0 mg/kg NNNMU decreased PaO2 on room air to 40 torr (phase I) and 30 torr (phase II). Within 5 to 7 days after injection, PaO2 decreased to 40 torr, Qsp/Qt at FIO2 0.21 increased from 0.18 to 0.70, Qsp/Qt at FIO2 1.0 increased to 0.55, and pulmonary vascular resistance index (PVRI) increased from 213 +/- 37 to 407 +/- 142 dyne X sec/cm5 X m2 (p less than .05). However, a decrease in mean arterial pressure (MAP) from 153 +/- 16 to 131 +/- 32 mm Hg was the only significant hemodynamic change. At phase II, decreased systemic vascular resistance index (SVRI) was the only significant hemodynamic alteration. We conclude that single subcutaneous injection of NNNMU produces hemodynamic and pulmonary dysfunction similar to that seen in human ARDS. This acute lung-injury model may be useful for evaluating different ARDS therapies.
皮下注射N-亚硝基-N-甲基脲（NNNMU）诱导的急性肺泡损伤与人类成人呼吸窘迫综合征（ARDS）的病理非常相似。然而，其对心血管功能的影响尚未得到评估。我们测量了7只狗的血流动力学变量以及静脉血掺杂（吸入氧分数为0.21时的Qsp/Qt）和分流分数（吸入氧分数为1.0时的Qsp/Qt）。当单次皮下注射8.0mg/kg NNNMU使室内空气中的动脉血氧分压（PaO2）降至40托（I期）和30托（II期）时，重复进行这些测量。注射后5至7天内，PaO2降至40托，吸入氧分数为0.21时的Qsp/Qt从0.18增加到0.70，吸入氧分数为1.0时的Qsp/Qt增加到0.55，肺血管阻力指数（PVRI）从213±37增加到407±142达因·秒/厘米5·平方米（p<0.05）。然而，平均动脉压（MAP）从153±16毫米汞柱降至131±32毫米汞柱是唯一显著的血流动力学变化。在II期，全身血管阻力指数（SVRI）降低是唯一显著的血流动力学改变。我们得出结论，单次皮下注射NNNMU会产生与人类ARDS中所见相似的血流动力学和肺功能障碍。这种急性肺损伤模型可能有助于评估不同的ARDS治疗方法。
