Age-Related Differences in Vascular Effects of Pentoxifylline in Isolated Perfused Ferret Lungs

Abstract

We have determined the magnitude and sites of action of pentoxifylline (PTX), a methylxanthine derivative, in the adult and 3- to 4-week old ferret pulmonary circulation. Lungs of 8 ferrets, four 3- to 4-week-old and 4 adult, were isolated and perfused with blood. During perfusion, blood flow was kept constant, as were airway and left atrial pressures (6 and 8 cm H2O respectively, zone 3 conditions). In all lungs, pulmonary artery pressure was measured continuously and the circulation was partitioned into arteries, microvessels and veins, by measurement of pressures in 20-50 microns diameter subpleural arterioles and venules using the micropipette-servonulling method. Pressures were obtained in each lung during baseline, after vasoconstriction with hypoxia, and again after the infusion of PTX, 20 mg/kg, during hypoxia. We found that with hypoxia, total vascular resistance increased by approximately 90% in both adult and neonatal lungs; arterial and venous resistances increased by 100-180% in both age groups, with little change in microvascular resistance. PTX resulted in a significant decrease in total vascular resistance, due to a decrease in resistance in both arteries and veins. The decrease in resistance with PTX was greater in adult lungs (of the increase in resistance induced by hypoxia, 80% was eliminated by PTX) than in 3- to 4-week old lungs (51% elimination of tone induced by hypoxia). This difference was mainly due to a smaller reduction in arterial resistance with PTX in 3- to 4-week-old lungs. We conclude that PTX is a powerful pulmonary vasodilator in ferrets and that its effectiveness as a vasodilator depends on the age of the animal, the older animal showing greater responsiveness.