Effect of Altered Inflation on Pulmonary Uptake of Methylglyoxal Bis(Guanylhydrazone)

Abstract

The effects of increased pulmonary ventilation on uptake of an exogenous, nonme-tabolized polyamine analog, methylglyoxal bis(guanylhydrazone) [MGBG] were investigated in rat lungs perfused in situ with buffer containing 4.5% bovine serum albumin, 5.6 mM glucose and plasma levels ofamino acids. The perfusate was equilibrated and the lungs were ventilated with warmed, humidified O₂/N₂/CO₂ (20:75:5). A 28% increase in lung inflation rapidly accelerated MGBG uptake at low (1.5 μM) but not at high (50 μM) substrate concentration, a change which appeared to reflect a decrease in the apparent Km of the uptake pathway. This effect was not associated with acute alterations in pulmonary vascular permeability or resistance, nor with instability of the preparations. Taken with observations made previously, these results suggest that deformation of the tissue by increased inflation may account for increased MGBG uptake by lungs from rats subjected to partial pneumonectomy.