The isolated heart-lung preparation in the cat. An in situ model to study the role of the lungs in the disposition of drugs.
In the search for drugs with an extreme short time course of action, compounds should be developed that are rapidly distributed to and temporarily stored in well-perfused organs. Since the lungs receive the complete cardiac output and have the ability to temporarily store drugs, we have developed an in situ, isolated lung preparation in the cat to study the contribution of the lungs to the disposition of drugs. The cat's own heart perfuses the lung in situ with autologous blood. The circulation between the left ventricle and the right atrium is short-circuited via an aorta-caval shunt. The right forelimb is added to study pharmacodynamics simultaneously (only for muscle relaxants). Validation of the model for 180 min of perfusion showed complete isolation of the organs without major biochemical changes or edema and a stable muscle response. In pilot experiments with two structurally related muscle relaxants, initial muscle relaxation was followed by spontaneous recovery of neuromuscular function and a gradually decreasing plasma concentration, indicating partial disposition by the lungs. This was confirmed by direct concentration measurements in the lung. The present model may provide a powerful experimental tool to elucidate the role of the lungs in the disposition of drugs.
Beaufort
A M
AM
Research Group for Experimental Anesthesiology and Clinical Pharmacology, University of Groningen, The Netherlands.
Wierda
J M
JM
Houwertjes
M C
MC
Kleef
U W
UW
Meijer
D K
DK
D000418:Albumins / Q000493:pharmacokinetics; D000732:Androstanols / Q000493:pharmacokinetics; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002415:Cats; D005112:Extracorporeal Circulation; D005552:Forelimb; D006321:Heart / Q000502:physiology*; D007457:Iodine Radioisotopes; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008168:Lung / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008954:Models, Biological; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D003473:Neuromuscular Nondepolarizing Agents / Q000097:blood / Q000493:pharmacokinetics*; D010477:Perfusion; D010976:Platelet Count; D000077123:Rocuronium; D014673:Vecuronium Bromide / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology
D000418:Albumins; D000732:Androstanols; D001798:Blood Proteins; D007457:Iodine Radioisotopes; D007527:Isoenzymes; D003473:Neuromuscular Nondepolarizing Agents; C058720:Org 7617; D014673:Vecuronium Bromide; D007770:L-Lactate Dehydrogenase; D000077123:Rocuronium