THE ISOLATED HEART-LUNG PREPARATION IN THE CAT - AN INSITU 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, c ompounds should be developed that are rapidly distributed to and tempo rarily stored in well-perfused organs. Since the lungs receive the com plete 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 c at's own heart perfuses the lung in situ with autologous blood. The ci rculation between the left ventricle and the right atrium is short-cir cuited via an aorta-caval shunt. The right forelimb is added to study pharmacodynamics simultaneously (only for muscle relaxants). Validatio n of the model for 180 min of perfusion showed complete isolation of t he organs without major biochemical changes or edema and a stable musc le response. In pilot experiments with two structurally related muscle relaxants, initial muscle relaxation was followed by spontaneous reco very of neuromuscular function and a gradually decreasing plasma conce ntration, indicating partial disposition by the lungs. This was confir med by direct concentration measurements in the lung. The present mode l may provide a powerful experimental tool to elucidate the role of th e lungs in the disposition of drugs.