The isolated heart-lung preparation in the cat. An in situ model to study the role of the lungs in the disposition of drugs.
J Pharmacol Toxicol Methods
; 29(3): 147-56, 1993 Jun.
Article
in En
| MEDLINE
| ID: mdl-8103378
ABSTRACT
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Neuromuscular Nondepolarizing Agents
/
Heart
/
Lung
/
Models, Biological
Limits:
Animals
Language:
En
Journal:
J Pharmacol Toxicol Methods
Journal subject:
FARMACOLOGIA
/
TOXICOLOGIA
Year:
1993
Document type:
Article
Affiliation country:
Netherlands