MECHANICAL VENTILATION-INDUCED PULMONARY-EDEMA - INTERACTION WITH PREVIOUS LUNG ALTERATIONS

The risk of lung injury due to alveolar overdistension during mechanical ventilation has been clearly delineated in healthy animals with intact lungs. In contrast, the effect of high-volume ventilation (HV) on previously injured lungs is less well documented: whether HV would simply add its own deleterious effects or act synergistically with previous injury has not been addressed. We compared the effect of 7 ml/kg body weight tidal volume mechanical ventilation for 2 min with that of 25 (HV25), 33(HV33), and 45(HV45) ml/kg body weight HV in anesthetized rats previously exposed or not exposed to alpha-naphthylthiourea (ANTU). ANTU alone produced moderate permeability edema with significant increases in extravascular lung water (Qwl), dry lung weight (DLW), and albumin distribution space in lungs (ASp). HV alone resulted in a permeability edema in which severity was dependent on the magnitude of the tidal volume. The effects of HV25 and HV33 and those of ANTU were only additive, as indicated by the absence of any significant two-factor (ANTU-HV) interaction by analysis of variance (ANOVA). In contrast, HV45 after ANTU produced significantly greater increases in Qwl, DLW, and ASp than expected from the sum of the effects of either insult alone. Two-way ANOVA disclosed two-factor interactions with p values < 0.001, < 0.02, and < 0.01 for Qwl, DLW, and ASp, respectively, indicating synergistic adverse effects on pulmonary edema. Synergy was also observed between the effects of HV45 and the duration of anesthesia (a situation known to produce alveolar surface tension alterations in spontaneously breathing animals) prior to HV; HV45 produced more edema when anesthesia occurred 2 h before HV as compared with 30 min before HV. Two-factor interactions (duration of anesthesia-HV45) with p values < 0.05 and < 0.01 were found for Qwl and ASp, respectively, whereas duration of anesthesia did not affect the DLW increase, suggesting a role of increased filtration in the worsening of edema. Analysis of respiratory system compliance revealed that compliance at the beginning of HV45 correlated with the amount of edema after HV45 in both ANTU-treated and untreated animals anesthetized 30 min or 2 h before HV. These results suggest that previous lung alterations of different types and severity may synergistically potentiate ventilation-induced injury.