We perfused in situ isolated left lower lung lobes at a steady flow rate in zone 3 condition. When the lobar arterial inflow was suddenly occluded, the arterial pressure (Pa) fell rapidly and then more slowly. When the lobar venous outflow was suddenly occluded, the venous pressure (Pv) rose rapidly and then continued to rise more slowly. The rapid changes in Pa and Pv with inflow and outflow occlusion, respectively, represent the pressure drops across the arterial (delta Pa) and venous (delta Pv) relatively indistensible vessels. The total arteriovenous pressure difference (delta Pt) minus delta Pa + delta Pv gives the pressure drop across the vessels in the middle (delta Pm) that are much more distensible. Serotonin and histamine infusion increased delta Pa and delta Pv, respectively, but left delta Pm unchanged. delta Pa and delta Pv, but not delta Pm, increased as flow rate was increased. The studies with varying flow rate and venous pressures suggested that the arteries and veins became resistant to distension when their transmural pressures exceeded 10--5 Torr, respectively. Under the conditions studied, the middle nonmuscular segment contributed a major fraction of the vascular compliance and less than 16% of the total resistance. The muscular arteries and veins contributed equally to the remaining resistance. We conclude that the arterial and venous occlusion method is a useful technique to describe the resistance and compliance of different segments of the pulmonary vasculature.

Postobstructive pulmonary vasculopathy (POPV) was produced by chronic ligation (120 days) of the left main pulmonary artery of seven dogs. To explain the abnormal physiological changes found using arterial and venous occlusion (AVO) in POPV (J. Appl. Physiol. 69: 1022-1032, 1990), the light-microscopic morphology, morphometry (n = 5), and ultrastructure (n = 6) of ligated left lower lobes were compared with contralateral control right lower lobes. First, there was a proliferation of bronchial vessels around pulmonary vessels and airways to explain bronchial blood flow rates of 330 ml/min in left lower lobes. The walls of the bronchial vessels contained smooth muscle with minimal elastic tissue and prominent myoendothelial junctions. Second, focal bronchopulmonary anastomoses were seen in pulmonary arteries approximately equal to 100 microns diam, which is consistent with our conclusion that the major site of communication is at the precapillary level and suggests that the limit between arterial and middle segments defined by AVO may lie in arteries of approximately equal to 100 microns. Third, to explain the increased arterial resistance in POPV, the pulmonary arteries had an increased percent medial muscle thickness, peripheral muscularization, and focal intimal thickening but had no plexiform lesions. The ultrastructure of the arteries revealed new intimal cells and numerous myoendothelial junctions rarely found in controls. Capillaries and veins were only subtly altered. Fourth, the hyperreactivity of arteries to serotonin and of veins to histamine found using AVO was partially explained by the increased medial thickness and decreased diameter but may also be due to increased receptor concentration or related to the myoendothelial junctions. We conclude that most of the hemodynamic alterations in POPV are related to morphological abnormalities and that this model has clinical and experimental relevance in the study of bronchopulmonary vascular interactions.

To explain the changes in pulmonary vascular resistance (PVR) with positive- and negative-pressure inflation (PPI and NPI, respectively), we studied their effects in isolated canine left lower lobes perfused at constant flow rate. The venous pressure was kept constant relative to atmospheric pressure during lung inflation. The total arteriovenous pressure drop (delta Pt) was partitioned with the arterial and venous occlusion technique into pressure drops across arterial and venous segments (large indistensible extra-alveolar vessels) and a middle segment (small distensible extra-alveolar and alveolar vessels). PPI caused a curvilinear increase in delta Pt due to a large Starling resistance effect in the alveolar vessels associated with a small volume-dependent increase in the resistance of alveolar and extra-alveolar vessels. NPI caused an initial decrease in delta Pt due to reduction in the resistance of extra-alveolar vessels followed by an increase in delta Pt due to a volume-dependent increase in the resistance of all vessels. In conclusion, we provided for the first time evidence that lung inflation results in a volume-dependent increase in the resistance of both alveolar and extra-alveolar vessels. The data suggest that while the volume-related changes in PVR are identical with PPI and NPI, there are pressure-related changes that can be different between the two modes of inflation.

We applied the arterial and venous occlusion technique in an in situ, isolated left lower lobe preparation of a dog lung to compare the effects of hypoxia with the effects of airway pressure elevation, and the infusion of serotonin, norepinephrine, and histamine. The total arteriovenous pressure drop across the lobe was partitioned longitudinally into pressure drops across the relatively indistensible arteries (delta Pa) and veins (delta Pv) and across the middle distensible vessels (delta Pm). Hypoxia increased primarily delta Pm, as did elevation of airway pressure, whereas the vasoactive drugs increased either delta Pa or delta Pv. The increases in pulmonary arterial pressure (Pa) caused by hypoxia and by elevation of airway pressure were independent of blood flow rate, but increases in Pa induced by the vasoactive drugs were dependent on flow rate. We conclude that in the dog hypoxia acts primarily on small distensible vessels, whereas pulmonary vasoactive drugs constrict the relatively indistensible arteries and veins. It is possible that the increase in pulmonary vascular resistance during hypoxia did not involve smooth muscle contraction.

Chronic unilateral pulmonary arterial ligation has been touted as a model of arteriopathy resulting in a tremendous increase in anastomotic bronchial flow (Qbr) via collaterals. To investigate its effects on the pulmonary vasculature, we ligated the left main pulmonary artery of seven dogs and 120 days later pump perfused their left lower lobes (LLL) via a cannula in the pulmonary artery at pulmonary arterial flow (Qpa) of 250 ml/min. We measured Qbr (330 ml/min) and compared LLL with control contralateral right lower lobes (RLL) and three LLL from normal dogs. Pressure-flow (P-Q) curves were obtained by varying Qpa. With arterial and venous occlusion we measured total, arterial, venous, and middle segment resistances under baseline conditions, after serotonin and histamine, either with or without Qpa and with antegrade and retrograde Qbr. Light microscopy was done postmortem. The slope of the P-Q curve was 33.4 mmHg.l-1.min in the ligated lobes compared with 15.9 in the controls, attributable by the occlusion technique mainly to a rise in arterial resistance (22.4 mmHg.l-1.min compared with 7.4 in the controls) with a small rise in venous resistance. This was explained by significant arterial medial muscle thickening and some loss of LLL volume. The arterial segment was markedly hypersensitive to serotonin, and the venous segment was mildly hypersensitive to histamine compared with controls. The occlusion data also enabled us to model the point of entry of the bronchial circulation into the pulmonary circuit at the precapillary level and to calculate bronchial vascular resistance. We conclude that postobstructive vasculopathy substantially raises pulmonary vascular resistance, mainly upstream from the site of entry of the bronchial circulation. The role of the latter may be to keep it from rising excessively in the segments it perfuses, i.e., the middle and venous ones.