Influence of temperature and plasma protein on doxorubicin uptake by isolated lungs

To examine the influence of hyperthermia and plasma albumin binding on doxorubicin uptake by the isolated perfused lung, and on some indices of the physiologic stability of the lung, rabbit lungs were perfused in a recirculating system with a physiologic salt solution containing either 5% bovine serum albumin or 5% dextran, and uptake of doxorubicin from the perfusate into the lungs was studied at 36°C and 43°C. The rate of doxorubicin uptake by the lung was approximately doubled by increasing the lung temperature from 36°C to 43°C. The impact of albumin binding on the doxorubicin uptake was mainly to decrease the tissue to perfusate concentration ratio at equilibrium. Perfusion pressure, lung compliance, lung weight, and glutathione efflux were measured as indicators of the status of the perfused lungs during the perfusion period. In general, the changes in these variables indicate that the deterioration with time was greater at 43°C than at 36°C, regardless of the perfusate composition, and that at 36°C the lungs were more stable when albumin was present in the perfusate.