Effect of exogenous cAMP and aminophylline on alveolar and lung liquid clearance in anesthetized sheep

A substantial body of evidence indicates that active transport of ions is important in modulating the resolution process of pulmonary edema. The biochemical regulation of this ion transport mechanism is still under investigation. In this study we evaluated the effect of an adenosine 3',5'-cyclic monophosphate (cAMP) analogue [dibutyryl cAMP (DBcAMP)] and a phosphodiesterase inhibitor (aminophylline) given alone or together on lung liquid and protein clearance. To study lung liquid and protein clearance, we measured the removal of 100 ml of autologous serum from the air spaces of anesthetized and ventilated adult sheep. Either serum alone or serum mixed with 10(-3) M DBcAMP, 10(-3) M or 10(-5) M aminophylline, or 10(-3) M aminophylline plus 10(-3) M DBcAMP was instilled. After 4 h, the residual lung water was 73.5 +/- 8.7 ml when serum alone was instilled and 56.8 +/- 13.6 ml when aminophylline and DBcAMP were given together. Neither aminophylline nor DBcAMP alone increased lung liquid clearance. However, the increase in clearance cannot be explained by an increase in protein clearance or changes in the pulmonary hemodynamics. These data suggest that the cAMP second messenger system can stimulate lung liquid clearance in vivo.