The study of the pulmonary vessels presents numerous difficulties, even in open chest experiments, because these vessels are placed between the right and the left heart. Therefore, changes of flow and pressure due to changes of right or left cardiac function are reflected by passive changes in caliber of the pulmonary vessels. The effect of drugs or nerve stimuli on the vessels of the lungs themselves is further complicated by the weakness of their musculature and by the fact that the pulmonary capillaries may be distended through either dilatation of the arterioles or contraction of the venules.In order to study changes of filling of the lung vessels, the following technique was employed:1. Right heart catheterization through a jugular vein and penetration of the catheter into the main pulmonary artery.2. Left heart catheterization through a femoral artery and penetration into the left atrium.3. Placement of a third catheter into the other femoral artery for recording peripheral pressure. 4. Opening of the chest following tracheotomy and artificial respiration. Placement of a pulmonary lobe between a photocell and a source of light. 5. Permanent distention of the lungs with a continuous jet of oxygen (or air) reaching the bifurcation of the trachea through a catheter. In later experiments, artificial respiration with air was continued throughout the experiment and the lobe under study was kept distended with a jet of nitrogen. 6. Use of one strain-gage and two electromanometers for recording pressures, and use of a chopper-amplifier connected to the photocell. 7. Use of a Sanborn Polyviso with direct-writing tracings recorded at a speed of 1 mm/sec. 8. Injection of drugs through cannulation of the right jugular vein. ACTION OF DRUGS ON THE PULMONARY VESSELSWith the above described method, the effects of 42 injections of drugs have been studied in 9 successful animal experiments. The drugs were:(a) Epinephrine in doses from 0.1 to 1 mg. (b) Nor-1-epinephrine in doses from 0.2 to 3 mg. (c) Histamin in doses from 1 to 5 mg. (d) Acetylcholine in doses from 2 to 5 mg. (e) Serotonin in doses from 2 to 15 mg.Isolated experiments have been made also with pitressin, peptone, and choledyl.

The mechanism of pulmonary edema caused by stimulation of the central nervous system was studied in 33 dogs. Stimulation was obtained by the intracisternal injection of veratrine, or of air or saline under high pressure, or by electric stimulation of the hypothalamus. Pressure changes in the pulmonary artery, left atrium and left ventricle were recorded by means of three catheters introduced through the right external jugular vein and the left femoral artery. Experiments were performed with closed or open chest, and following ligation of the thoracic aorta and inferior cava. Lung opacity was studied as a means to estimate the blood content of this organ. Data obtained in closed-chest experiments suggest that a blood shift from the systemic to the pulmonary circulation may be a factor in veratrine-induced pulmonary edema. This was confirmed by the observation that, following mechanical exclusion of the systemic circulation, no pulmonary edema occurred while the changes of left ventricular pressure were minimal and inconstant. In these animals, pulmonary artery pressure still rose indicating vasoconstriction while an increase of lung opacity suggested that the vasoconstriction was greater in the pulmonary veins than in the arteries. Injection of air or saline under high pressure into the cisterna magna and faradic stimulation of the hypothalamus caused pulmonary hypertension, even after exclusion of the systemic circulation. In these experiments, a decreased lung opacity suggested that the pulmonary constriction was greater on the arterial than on the venous side. These findings are offered as evidence that the caliber of the pulmonary vessels may be influenced by central nervous system stimulation, an additional element to be considered in the mechanism of pulmonary edema.

The effect of various operative procedures and tissue extracts on epinephrine-induced pulmonary edema (EPE) was studied in 338 rabbits. Anesthesia and laparotomy with manipulation of the viscera had a definite protective effect against EPE. Similar effects were obtained with the intraperitoneal injection of a foreign substance or pretreatment with ACTH or adrenal cortex steroids. This protection is believed to be the result of adrenal cortical activation by stress. Splenectomy had a protective effect against EPE which was greater than that of sham operations. The injection of splenic extract in splenectomized animals decreased survival time and increased the severity of the edema, whereas injection of hepatic extract had a less marked effect. Both unilateral and bilateral nephrectomy had a protective effect against EPE.