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 degrees C and 43 degrees C. The rate of doxorubicin uptake by the lung was approximately doubled by increasing the lung temperature from 36 degrees C to 43 degrees 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 degrees C than at 36 degrees C, regardless of the perfusate composition, and that at 36 degrees C the lungs were more stable when albumin was present in the perfusate.
Bongard
R D
RD
Department of Physiology, Medical College of Wisconsin, Milwaukee.
Roerig
D L
DL
Johnston
M R
MR
Linehan
J H
JH
Dawson
C A
CA
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism / Q000502:physiology*; D004317:Doxorubicin / Q000493:pharmacokinetics*; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D008170:Lung Compliance / Q000502:physiology; D009929:Organ Size / Q000502:physiology; D010477:Perfusion; D011485:Protein Binding; D011817:Rabbits; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013696:Temperature
D001798:Blood Proteins; D012710:Serum Albumin, Bovine; D004317:Doxorubicin; D005978:Glutathione