Trimetaphan (Arfonad), which acts as a histamine-releasing agent in dogs, was observed to increase the shunt of blood through the lungs. Although external examination of the lungs showed no appreciable collapse, more detailed examination of lungs fixed by perfusion showed that the shunt could be explained on the basis of alveolar collapse and there was no need to postulate the opening of anatomical shunts. Histamine-releasing agents or histamine produced rapid, shallow breathing, which persisted after inflation of the lungs sufficient to restore the elastic and non-elastic resistance of the lungs to normal. It seems possible that the rapid, shallow breathing is due to sensitization of vagal nerve endings by the histamine or by some other substance released from the mast cells.
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