Background: The combination of high PEEP and low tidal volume (V(T)) decreases some risks of mechanical ventilation, including pulmonary overdistention, damage due to cyclic opening and closing of the alveoli, and inflammatory responses that can lead to multiple-organ dysfunction. We hypothesized that high V(T) and high PEEP induce mesenteric microcirculatory disturbances and that those disturbances would be attenuated by pentoxifylline, which is anti-inflammatory.
Methods: We anesthetized (isoflurane 1.5%), tracheostomized, and mechanically ventilated 57 male Wistar rats with PEEP of 10 cm H(2)O and F(IO(2)) of 0.21 for 2 hours. One group received low V(T) (7 mL/kg), another group received high V(T) (10 mL/kg), and a third group received high V(T) plus pentoxifylline (25 mg/kg). We measured mean arterial pressure, respiratory mechanics, mesenteric blood flow, and leukocyte-endothelial interactions.
Results: The mean arterial pressure was similar among the groups at baseline (108 mm Hg [IQR 94-118 mm Hg]) and after 2 hours of mechanical ventilation (104 mm Hg [IQR 90-114 mm Hg]). Mesenteric blood flow was also similar between the groups: low V(T) 15.1 mL/min (IQR 12.4-17.7 mL/min), high V(T) 11.3 mL/min (IQR 8.6-13.8 mL/min), high-V(T)/pentoxifylline 12.4 mL/min (10.8-13.7 mL/min). Peak airway pressure after 2 hours was lower (P = .03) in the low-V(T) group (10.4 cm H(2)O [IQR 10.2-10.4 cm H(2)O]) than in the high-V(T) group (12.6 cm H(2)O [10.2-14.9 cm H(2)O]) or the high-V(T)/pentoxifylline group (12.8 cm H(2)O [10.7-16.0 cm H(2)O]). There were fewer adherent leukocytes (P = .005) and fewer migrated leukocytes (P = .002) in the low-V(T) group (5 cells/100 μm length [IQR 4-7 cells/100 μm length] and 1 cell/5,000 μm(2) [IQR 1-2 cells/5,000 μm(2)], respectively) and the high-V(T)/pentoxifylline group (5 cells/100 μm length [IQR 3-10 cells/100 μm length] and 1 cell/5,000 μm(2) [IQR 1-3 cells/5,000 μm(2)], respectively) than in the high-V(T) group (14 cells/100 μm length [IQR 11-16 cells/100 μm length] and 9 cells/5,000 μm(2) [IQR 8-12 cells/5,000 μm(2)], respectively).
Conclusions: Low V(T) with high PEEP was lung-protective, and early pentoxifylline reduced the inflammatory response to high V(T) with high PEEP (and presumed lung overdistention) during mechanical ventilation.