Modulation by endogenous opioids of pulmonary vasoconstrictor response to acute lung injury

The effects of endogenously generated opioids on distribution of pulmonary perfusion (as assessed by radiolabeled microspheres) and overall gas exchange in acute acid-induced lung injury were studied. In 14 anesthesized dogs, sufficient acid was given to one lung to double shunt fraction (Q̇s/Q̇T) from 14.2 ± 0.8 to 32.4 ± 2.6% (SE). This resulted in a significant decrease in PO₂ from 495 ± 9 to 136 ± 21 Torr, cardiac output from 2.47 ± 0.27 to 1.46 ± 0.15 l/min, and blood pressure from 139 ± 3 to 116 ± 5 mmHg and a significant rise in pulmonary arterial pressure from 9.6 ± 0.8 to 14.9 ± 0.8 mmHg. After acid instillation, microsphere distribution to the injured lung segments decreased to 50% of the base-line value. At the same time, microsphere distribution in the normal segments increased to 160% of base line. In 7 of the 14 dogs the effects of naloxone (1 mg/kg) given after lung injury were compared with the other 7 animals that were given saline. Naloxone administration caused a significant redistribution of regional pulmonary perfusion such that microsphere distribution in the injured lung segments increased by a factor of 2 at 35 min compared with the animals given saline. Consistent with this finding, Q̇s/Q̇t in the naloxone group increased to 34.7 ± 5.0% at 35 min, whereas that of the saline group decreased to 28.2 ± 2.5%. The difference between the two groups was significant at 35 min. These changes occurred without further alterations in cardiac output, pulmonary arterial pressure, or systemic blood pressure in either group. These findings suggest that endogenous opioids contribute to the vasoconstriction associated with acute acid-induced lung injury.