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The release and detection of bronchoactive substances by serially perfused isolated lungs

A residual increase in air overflow volume during anaphylaxis of the Konzett Rossler preparation of guinea-pig lungs in vivo occurred after pretreatment of the animal with antagonists of histamine, 5-hydroxytryptamine (5-HT), the Hounslow preparation of slow-reacting substances in anaphylaxis (SRS-A-H), and bradykinin (Collier & James, 1967). This increase was intensified by blockade of /3-receptors for adrenaline and was not prevented by destruction of the central nervous system. That papaverine lessened the residual effect suggested that it was wholly or partly due to bronchoconstriction. Suggested mechanisms, by which this residual bronchoconstriction might occur, included the failure of the antagonists used to suppress a known humoral factor and the release of an unidentified factor not susceptible to these antagonists (Collier & James, 1967). A preparation of serially perfused isolated lungs described below has been developed to explore these possibilities. Guinea-pig lungs were isolated by the technique of Bhattacharya & Delaunois (1955). The guinea-pig was lightly anaesthetized with phenobarbitone (30 mg/kg, i.p.), the trachea was cannulated and artificial ventilation was established with a pump of 5-8 ml stroke volume at a rate of 40 strokes/min. The pulmonary artery and vein were cannulated and the lungs perfused by a peristaltic pump at 8-12 ml/ min with Tyrode solution containing 2.5% w/v polyvinyl pyrrolidone at 37". The lungs were then excised and suspended in a heating jacket containing water at 37" (Fig. 1). The pressure in the trachea was measured by a pressure transducer in the side-arm of the tracheal cannula. The perfusion pressure was measured by a Statham pressure transducer from a needle inserted above the pulmonary artery. The lungs were suspended from a strain gauge to detect increase in weight and hence oedema formation.