title: Alveolar inflation during generation of a quasi-static pressure/volume curve in the acutely injured lung.
abstract: OBJECTIVE
  Lower 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.
  
  
  METHODS
  Prospective, observational, controlled study.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Eight adult pigs.
  
  
  METHODS
  Pigs 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.
  
  
  RESULTS
  The 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 microm2) to 40 mL (12,935 +/- 1725 microm2) but did not increase further (220 mL, 14,058 +/- 1740 microm2) with lung inflation. Type III alveoli initially recruited with a relatively small area (20 mL lung volume, 798 +/- 797 microm2) and progressively increased in area throughout lung inflation (120 mL, 7302 +/- 1405 microm2; 220 mL, 11,460 +/- 1078 microm2)
  
  
  CONCLUSIONS
  The 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 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.
authors.affiliation: Departments of Surgery, SUNY Upstate Medical University, Syracuse, NY, USA.
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Schiller
authors.forename: Jay
authors.initials: J
authors.lastname: Steinberg
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Halter
authors.forename: Ulysse
authors.initials: U
authors.lastname: McCann
authors.forename: Monica
authors.initials: M
authors.lastname: DaSilva
authors.forename: Louis A
authors.initials: LA
authors.lastname: Gatto
authors.forename: Dave
authors.initials: D
authors.lastname: Carney
authors.forename: Gary
authors.initials: G
authors.lastname: Nieman
mesh_terms: D000403:Airway Resistance; D000818:Animals; D007091:Image Processing, Computer-Assisted; D008170:Lung Compliance; D008176:Lung Volume Measurements; D018715:Microscopy, Video; D011136:Polysorbates / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000473:pathology / Q000503:physiopathology*; D011663:Pulmonary Surfactants / Q000494:pharmacology; D012128:Respiratory Distress Syndrome / Q000473:pathology / Q000503:physiopathology*; D015656:Respiratory Mechanics; D013501:Surface-Active Agents / Q000494:pharmacology; D013552:Swine; D013990:Tidal Volume
chemical_list: D011136:Polysorbates; D011663:Pulmonary Surfactants; D013501:Surface-Active Agents