Inflation-associated increases in lung polyamine uptake: role of altered pulmonary vascular flow

Unilateral pneumonectomy in rats leads to rapid compensatory growth of the remaining lung. Previous studies showed that postoperative increases in lung mass are preceded by enhanced uptake of exogenous polyamines and by alterations in adenosine 3',5'-cyclic monophosphate (cAMP) metabolism. These effects are both mimicked in lungs of intact animals subjected to increased inflation in vitro. Partial pneumonectomy also leads to increased flow to the contralateral lung associated with reduced pulmonary vascular resistance. This raises the possibility that the postoperative metabolic response is initiated by changes in pulmonary artery pressure (Pa) or flow, rather than altered inflation. The present studies were designed to investigate this issue. Uptake of exogenous [14C]spermidine by isolated perfused rat lungs was examined over a wide range (greater than 4-fold) of pulmonary flow and ventilation at fixed PaS. Assessment of tissue metabolism from rates of protein synthesis suggested stability of the isolated lung preparations. Apnea (0 ventilation) had no effect on spermidine uptake or flow rate, compared with lungs evaluated under normal conditions of ventilation (inspiratory pressure, 15 cmH2O; positive end expiratory pressure, 2 cmH2O; rate, 70 breaths/min). At both high and low Pa (at a flow rate of 37 +/- 1 and 11 +/- 2 ml/min, respectively, with 0 ventilation), removal of the left lung from the perfusion circuit increased specific right lung flow rate greater than 30% but had no effect on spermidine uptake. Similar alterations in flow rate to the right or both apneic lungs had no effect on the tissue content of cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)