Reparative changes following oxygen-induced lung injury: effect on serotonin disposition and metabolism.

Exposure of mice to normobaric 100% oxygen for 72 hr has been shown to damage lung capillary endothelial cells and to markedly alter the pulmonary disposition and metabolism of endogenous serotonin (5-HT) and exogenous [3H]5-HT in a time-dependent manner. We have extended these studies to examine the reparative changes occurring in lung following moderate oxygen-induced injury. Pulmonary angiotensin converting enzyme (ACE) activity, a biochemical marker of endothelial cell injury, was decreased after a 72-hr oxygen exposure and progressively increased above control levels during the recovery period (130%, 168 hr) and paralleled lung protein content. The pulmonary disposition of [3H]5-HT also provided an index of endothelial cell function. Lung levels of [3H]5-HT were elevated 183% (0 hr) and 200% (24 hr) and returned to control values by 72 hr of air recovery. Pulmonary edema followed a similar time-course that corresponded to reported ultrastructural changes. The circulating platelet concentration progressively decreased from control values at 0 hr to 68% of control of 168 hr. In contrast to lung where 5-HT was significantly elevated during the early reparative period, platelet 5-HT content was significantly decreased and, like lung, returned to control values by 72 hr. The two forms of lung monoamine oxidase (MAO) showed different responses during the reparative phase. Type A MAO was slightly elevated throughout the recovery period. In contrast, type B MAO was decreased at 0 hr but increased throughout the reparative phase, being significantly elevated 128% at 72 hr and 139% at 168 hr. These data suggest that the lung is capable of readily recovering from moderate oxygen-induced injury and that certain biochemical parameters described herein provide useful indices of pulmonary microvascular function.