In sheep, anesthetized and intubated, bilateral cervical vagotomy produced no change in lung compliance (Cl), reduced inspiratory resistance to airflow, increased expiratory resistance to airflow, and changed the pattern of breathing. Electrical stimulation of the peripheral end of the cut vagus nerve produced an immediate increase in lung volume due to an increase in inspiratory tonus, a fall in Cl, an increase in resistance to airflow, and a decrease in heart rate and systemic arterial pressure. Pulmonary arterial pressure remained unchanged; pulmonary arterial resistance increased. These effects were blocked by atropine. The lung mechanics changes were partly reversed spontaneously, completely reversed by forced inflation, and potentiated by prostigmine. The effects on lung mechanics suggest that vagal stimulation in the sheep mainly affects the peripheral airways producing airway closure, and indicates the possibility of a nervous mechanism for the control of the number of ventilated lung units. compliance; total pulmonary resistance; inspiratory; tonus; peripheral airway reaction; respiratory pattern Submitted on December 6, 1962

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•Acute pulmonary microembolism causes pulmonary vasoconstriction and closure of the terminal airways. We have given reasons to suppose that these effects are not entirely explicable in terms of mechanical obstruction or neurogenic vasoconstriction and we have postulated that the effects of microembolism may be due, in part, to release of some humoral agent.1 "3 The experiments described below were designed to test this hypothesis. Methods MATERIALFourteen technically satisfactory experiments were carried out on 14 pairs of sheep. Members of each pair will be referred to as recipient (A) and donor (B). The mean weight of the recipients (A) was 33.6 kg and that of the donors (B) was 35.0 kg. OPERATIVE PROCEDURESThe supine animals were anesthetized with 10 to 15 mg/kg iv of pentothal sodium (Thiopentone) followed by an intravenous drip of 0.20 to 0.25 mg/kg/min pentothal sodium and 0.15 to 0.20 mg/kg/min heparin given in saline.Following anesthesia the trachea was intubated with a cuffed Magill tube. Catheterization of the pulmonary artery was carried out via a femoral vein and the femoral artery was cannulated. A needle was inserted into the intrapleural space and a small (60 to 100 ml) pneumothorax was induced. Rectal temperature was measured with a thermometer. PRESSURE MEASUREMENTSFemoral arterial, pulmonary arterial, intrapleural, and (whenever a double-lumen catheter was

The cardiopulmonary consequences of coli-lipopolysaccharide and staphylococcus toxin administration were studied in sheep. Circulatory changes consisted mainly of a marked rise in pulmonary arterial and pulmonary arterial wedge pressure (with left atrial pressure unchanged), and a fall in cardiac output and in systemic arterial pressure. Fall in the latter closely followed the onset of pulmonary hypertension. The respiratory response consisted mainly of a severe fall in lung compliance produced by terminal airway closure. Continued perfusion of the nonventilated alveoli resulted in venous admixture. Premedication with antihistaminic, antiserotonin, or adrenolytic agents failed to affect the response. Norepinephrine or hypertensin administered after toxin injection had virtually no effect while isoproterenol treatment reduced pulmonary arterial pressure, increased cardiac output, arterial oxygen saturation, and, in cases of endotoxin shock, promptly raised systemic arterial pressure. Endotoxin-resistant sheep proved nonresponsive to minor pulmonary embolism and to incompatible blood transfusion. It is suggested that a common mediator agent is responsible for the similar cardiopulmonary consequences of these three diverse conditions. Submitted on November 26, 1962

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