Hemodynamic alterations in canine acute lung injury induced with N-nitroso-N-methylurethane

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.