The Effects of Low and High Tidal Volume and Pentoxifylline on Intestinal Blood Flow and Leukocyte-Endothelial Interactions in Mechanically Ventilated Rats

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 H2O and F-IO2 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 H2O [IQR 10.2-10.4 cm H2O]) than in the high-V-T group (12.6 cm H2O [10.2-14.9 cm H2O]) or the high-V-T/pentoxifylline group (12.8 cm H2O [10.7-16.0 cm H2O]). There were fewer adherent leukocytes (P = .005) and fewer migrated leukocytes (P = .002) in the low-V-T group (5 cells/100 gm length [IQR 4-7 cells/100 mu m length] and 1 cell/5,000 mu m(2) [IQR 1-2 cells/5,000 mu m(2)], respectively) and the high-V-T/pentoxifylline group (5 cells/100 mu m length [IQR 3-10 cells/100 mu m length] and 1 cell/5,000 mu m(2) [IQR 1-3 cells/5,000 mu m(2)], respectively) than in the high-V-T group (14 cells/100 mu m length [IQR 11-16 cells/100 mu m length] and 9 cells/5,000 mu m(2) [IQR 8-12 cells/5,000 mu m(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.