Haemodynamic, gasometric and haematological effects of air infusion in dogs: leukotriene inhibition with U-60,257.

Air embolization has been shown to produce a reversible permeability-type of pulmonary oedema. The present study investigated the haemodynamic, gasometric and haematological changes associated with air infusion in the spontaneously breathing dog (weight 31 +/- 5 kg). Air was infused at a rate of 10 ml X min-1 for 60 min (10 dogs) or 180 min (5 dogs). During the air infusion, a dramatic increase in pulmonary artery pressure was associated with only a moderate increase in right atrial pressure and limited decreases in arterial pressure and in cardiac output. A marked decrease in end-tidal PCO2 reflected the increase in dead space. These changes were stable during air infusion, but rapidly reversed after the end of infusion. However, hypoxaemia, defined by a decreased PaO2/PAO2 ratio, deteriorated with time and was only partially reversible. At histological examination, interstitial pulmonary oedema was present around the pulmonary arterioles. Air infusion was associated with rapid decreases in circulating leukocytes and platelets and complement activation. Since leukotriene release might be associated with leukocyte activation in this model, seven additional dogs were pretreated by inhalation of 10 mg of the leukotriene inhibitor U-60,257. The increase in pulmonary vascular resistance and in pulmonary shunt were moderately reduced and the drop in circulating leukocytes and platelets was strikingly abolished in the treated animals. Air infusion in the spontaneously breathing dog represents a model of very stable and reversible pulmonary hypertension. It can reproduce important pathophysiological features implicated in the development of pulmonary oedema.(ABSTRACT TRUNCATED AT 250 WORDS)