Influence of chronic cigarette smoke exposure on the uptake and efflux of imipramine in the isolated perfused rat lung.

The pulmonary uptake and efflux of imipramine was determined in lungs removed from cigarette smoke-exposed and nonexposed rats. Using an isolated perfused lung preparation, the lung was perfused for 220 sec with medium containing 2.5 X 10(-7) M imipramine, followed by a 28-min drug-free perfusion. There was no significant difference (p less than 0.05) between either the rate or the amount of imipramine accumulated in the smoke-exposed and nonexposed animals. During the drug-free perfusion, the previously accumulated imipramine was released from two distinct pools (E1 and E2). Calculation of the total amount of effluxable imipramine indicated that in the nonexposed animals approximately 30% of the amount taken up did not efflux at a measurable rate but formed a "noneffluxable" pool. In the smoke-exposed animals, however, all of the accumulated imipramine appeared to be effluxable. These data demonstrate that there may be components of cigarette smoke which are sequestered by lung tissue at the binding sites associated with the noneffluxable pool of imipramine. The presence in cigarette smoke of components possessing such high pulmonary affinity may be a factor in cigarette smoke-mediated lung damage; this possibility is discussed.