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The left lung from a dog was removed, ventilated with negative pressure, and perfused with venous blood. Pulmonary arterial, venous, and alveolar pressures could be varied over a large range. The distribution of blood flow in the lung was measured with Xe133. Under these conditions, there was no blood flow above the level at which alveolar equaled arterial pressure (measured at the arterial cannula). Below this level there was a linear increase in blood flow down the lung when the venous pressure was kept low. Raising the venous pressure made the distribution of flow more uniform below the level at which venous and alveolar pressures were equal although flow still increased down this zone. The flow distribution could be completely accounted for by the mechanical effects of the pressure inside and outside the blood vessels which each behaved like a Starling resistance. It was possible to simulate the flow distributions found in man in various physiological and diseased states. pulmonary; hydrostatic effect; Starling resistance Submitted on November 15, 1963

We report the development of a 3D OrbiSIMS instrument for label-free biomedical imaging. It combines the high spatial resolution of secondary ion mass spectrometry (SIMS; under 200 nm for inorganic species and under 2 μm for biomolecules) with the high mass-resolving power of an Orbitrap (>240,000 at m/z 200). This allows exogenous and endogenous metabolites to be visualized in 3D with subcellular resolution. We imaged the distribution of neurotransmitters-gamma-aminobutyric acid, dopamine and serotonin-with high spectroscopic confidence in the mouse hippocampus. We also putatively annotated and mapped the subcellular localization of 29 sulfoglycosphingolipids and 45 glycerophospholipids, and we confirmed lipid identities with tandem mass spectrometry. We demonstrated single-cell metabolomic profiling using rat alveolar macrophage cells incubated with different concentrations of the drug amiodarone, and we observed that the upregulation of phospholipid species and cholesterol is correlated with the accumulation of amiodarone.

Inhaled radioactive CO2 is rapidly taken up by pulmonary blood. By external counting over the chest during breath holding, the clearance rate of radioactive CO2xs from the counting field can be recorded, and is proportional to the regional perfusion. In normal subjects, the clearance rate varied from about 20%/ sec. at the base of the lung to virtually nil at the apex, and the change was approximately linear with distance up the chest. The difference between upper and lower zones was reduced on moderate exercise and eliminated when the subject lay on his back. By relating the counting rate at the end of inspiration to the volume of lung in the counting field, the difference in ventilation between upper and lower zones was measured and found to be small. Variation in ventilation-perfusion ratio was thus determined. Alveolar-arterial O2 gradient expected from this ventilation-perfusion ratio inequality was calculated to be about 4 mm Hg. This suggests that the variation in blood flow between upper and lower parts of the lung in erect man accounts for the whole of the ventilation-perfusion ratio inequality in the normal lung. Submitted on November 23, 1959

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