Ulysse G. McCann

Altered alveolar mechanics in the acutely injured lung.

ObjectivesAlterations in alveolar mechanics (i.e., the dynamic change in alveolar size during tidal ventilation) are thought to play a critical role in acute lung injuries such as acute respiratory distress syndrome (ARDS). In this study, we describe and quantify the dynamic changes in alveolar mechanics of individual alveoli in a porcine ARDS model by direct visualization using in vivo microscopy. DesignProspective, observational, controlled study. SettingUniversity research laboratory. SubjectsTen adult pigs. InterventionsPigs were anesthetized and placed on mechanical ventilation, underwent a left thoracotomy, and were separated into the following two groups post hoc: a control group of instrumented animals with no lung injury (n = 5), and a lung injury group in which lung injury was induced by tracheal Tween instillation, causing surfactant deactivation (n = 5). Pulmonary and systemic hemodynamics, blood gases, lung pressures, subpleural blood flow (laser Doppler), and alveolar mechanics (in vivo microscopy) were measured in both groups. Alveolar size was measured at peak inspiration (I) and end expiration (E) on individual subpleural alveoli by image analysis. Histologic sections of lung tissue were taken at necropsy from the injury group. Measurements and Main Results In the acutely injured lung, three distinct alveolar inflation-deflation patterns were observed and classified: type I alveoli (n = 37) changed size minimally (I − E&Dgr; = 367 ± 88 &mgr;m2) during tidal ventilation; type II alveoli (n = 37) changed size dramatically (I − E&Dgr; = 9326 ± 1010 &mgr;m2) with tidal ventilation but did not totally collapse at end expiration; and type III alveoli (n = 12) demonstrated an even greater size change than did type II alveoli (I − E&Dgr; = 15,418 ± 1995 &mgr;m2), and were distinguished from type II in that they totally collapsed at end expiration (atelectasis) and reinflated during inspiration. We have termed the abnormal alveolar inflation pattern of type II and III alveoli “repetitive alveolar collapse and expansion” (RACE). RACE describes all alveoli that visibly change volume with ventilation, regardless of whether these alveoli collapse totally (type III) at end expiration. Thus, the term “collapse” in RACE refers to a visibly obvious collapse of the alveolus during expiration, whether this collapse is total or partial. In the normal lung, all alveoli measured exhibited type I mechanics. Alveoli were significantly larger at peak inspiration in type II (18,266 ± 1317 &mgr;m2, n = 37) and III (15,418 ± 1995 &mgr;m2, n = 12) alveoli as compared with type I (8214 ± 655 &mgr;m2, n = 37). Tween caused a heterogenous lung injury with areas of normal alveolar mechanics adjacent to areas of abnormal alveolar mechanics. Subsequent histologic sections from normal areas exhibited no pathology, whereas lung tissue from areas with RACE mechanics demonstrated alveolar collapse, atelectasis, and leukocyte infiltration. ConclusionAlveolar mechanics are altered in the acutely injured lung as demonstrated by the development of alveolar instability (RACE) and the increase in alveolar size at peak inspiration. Alveolar instability varied from alveolus to alveolus in the same microscopic field and included alveoli that changed area greatly with tidal ventilation but remained patent at end expiration and those that totally collapsed and reexpanded with each breath. Thus, alterations in alveolar mechanics in the acutely injured lung are complex, and attempts to assess what may be occurring at the alveolar level from analysis of inflection points on the whole-lung pressure/volume curve are likely to be erroneous. We speculate that the mechanism of ventilator-induced lung injury may involve altered alveolar mechanics, specifically RACE and alveolar overdistension.

Alveolar inflation during generation of a quasi-static pressure/volume curve in the acutely injured lung.

ObjectiveLower and upper inflection points on the quasi-static curve representing a composite of pressure/volume from the whole lung are hypothesized to represent initial alveolar recruitment and overdistension, respectively, and are currently utilized to adjust mechanical ventilation in patients with acute respiratory distress syndrome. However, alveoli have never been directly observed during the generation of a pressure/volume curve to confirm this hypothesis. In this study, we visualized the inflation of individual alveoli during the generation of a pressure/volume curve by direct visualization using in vivo microscopy in a surfactant deactivation model of lung injury in pigs. DesignProspective, observational, controlled study. SettingUniversity research laboratory. SubjectsEight adult pigs. InterventionsPigs were anesthetized and administered mechanical ventilation, underwent a left thoracotomy, and were separated into two groups: control pigs (n = 3) were subjected to surgical intervention, and Tween lavage pigs (n = 5) were subjected to surgical intervention plus surfactant deactivation by Tween lavage (1.5 mL/kg 5% solution of Tween in saline). The microscope was then attached to the lung, and the size of each was alveolus quantified by measuring the alveolar area by computer image analysis. Each alveolus in the microscopic field was assigned to one of three types, based on alveolar mechanics: type I, no visible change in alveolar size during ventilation; type II, alveoli visibly change size during ventilation but do not totally collapse at end expiration; and type III, alveoli visibly change size during tidal ventilation and completely collapse at end expiration. After alveolar classification, the animals were disconnected from the ventilator and attached to a super syringe filled with 100% oxygen. The lung was inflated from 0 to 220 mL in 20-mL increments with a 10-sec pause between increments for airway pressure and alveolar confirmation to stabilize. These data were utilized to generate both quasi-static pressure/volume curves and individual alveolar pressure/area curves. Measurements and Main ResultsThe normal lung quasi-static pressure/volume curve has a single lower inflection point, whereas the curve after Tween has an inflection point at 8 mm Hg and a second at 24 mm Hg. Normal alveoli in the control group are all type I and do not change size appreciably during generation of the quasi-static pressure/volume curve. Surfactant deactivation causes a heterogenous injury, with all three alveolar types present in the same microscopic field. The inflation pattern of each alveolar type after surfactant deactivation by Tween was notably different. Type I alveoli in either the control or Tween group demonstrated minimal change in alveolar area with lung inflation. Type I alveolar area was significantly (p < .05) larger in the control as compared with the Tween group. In the Tween group, type II alveoli increased significantly in area, with lung inflation from 0 mL (9666 ± 1340 &mgr;m2) to 40 mL (12,935 ± 1725 &mgr;m2) but did not increase further (220 mL, 14,058 ± 1740 &mgr;m2) with lung inflation. Type III alveoli initially recruited with a relatively small area (20 mL lung volume, 798 ± 797 &mgr;m2) and progressively increased in area throughout lung inflation (120 mL, 7302 ± 1405 &mgr;m2; 220 mL, 11,460 ± 1078 &mgr;m2) ConclusionThe normal lung does not increase in volume by simple isotropic (balloon-like) expansion of alveoli, as evidenced by the horizontal (no change in alveolar area with increases in airway pressure) pressure/area curve. After surfactant deactivation, the alveolar inflation pattern becomes very complex, with each alveolar type (I, II, and III) displaying a distinct pattern. None of the alveolar pressure/area curves directly parallel the quasi-static lung pressure/volume curve. Of the 16, only one type III atelectatic alveolus recruited at the first inflection point and only five recruited concomitant with the second inflation point, suggesting that neither inflection point was due to massive alveolar recruitment. Thus, the components responsible for the shape of the pressure/volume curve include all of the individual alveolar pressure/area curves, plus changes in alveolar duct and airway size, and the elastic forces in the pulmonary parenchyma and the chest wall.

Alveolar mechanics alter hypoxic pulmonary vasoconstriction.

ObjectivesHypoxic pulmonary vasoconstriction is the primary physiologic mechanism that maintains a proper ventilation/perfusion match, but it fails in diffuse lung injuries such as acute respiratory distress syndrome. Acute respiratory distress syndrome is associated with pulmonary surfactant loss that alters alveolar mechanics (i.e., dynamic change in alveolar size and shape during ventilation), converting normal stable alveoli into unstable alveoli. We hypothesized that alveolar instability stents open pulmonary microvessels and is the mechanism of hypoxic pulmonary vasoconstriction failure associated with acute respiratory distress syndrome. DesignProspective, randomized, controlled study. SettingUniversity research laboratory. SubjectsTen adult pigs. InterventionsAnesthetized ventilated pigs were prepared surgically for hemodynamic monitoring and were subjected to a right thoracotomy. An in vivo microscope was attached to the right lung, and the microvascular response to hypoxia (Fio2, 15%) was measured in a lung with normal stable alveoli and in a lung with unstable alveoli caused by surfactant deactivation (Tween lavage). Measurements and Main ResultsAlveolar instability, defined as the difference between alveolar area at peak inspiration and end expiration and assessed as a percentage change (I-E&Dgr;%), was significantly increased after Tween (23.9 ± 3.0, I-E&Dgr;%) compared with baseline (2.4 ± 1.0, I-E&Dgr;%). Alveolar instability was associated with the following microvascular changes: a) increased vasoconstriction (Tween, 14.9 ± 1.0%) in response to hypoxia compared with baseline (10.8 ± 1.2%, p < .05); and b) increased mean vascular diameter (Tween, 41.2 ± 1.5 &mgr;m) compared with the mean diameter at baseline (24.6 ± 1.0 &mgr;m, p < .05). ConclusionUnstable alveoli stent open pulmonary vessels, which may explain the failure of hypoxic pulmonary vasoconstriction in acute respiratory distress syndrome.