PURPOSE: To investigate the protective effect of pentoxifylline against the lung injury observed after intestinal ischemia (I) followed by a period of reperfusion (R). METHODS: Twenty-eight male Wistar rats were equally divided into 4 experimental groups and operated under ketamine-xylazine anesthesia. (1) Sham: falsely-operated animals; (2) SS+IR: intestinal ischemia was accomplished by clipping the superior mesenteric artery during 60 minutes, with an administration of a standard volume of saline solution (SS) 5 min before the end of the ischemia period; the clip was then releases or a 120-min period of reperfusion; (3) I+PTX+R: ischemia as above, PTX was administered (25 mg/kg) and the gut reperfused as above; (4) PTX+I+PTX+R: Five minutes before arterial occlusion PTX was administered; the superior mesenteric artery was then clipped for 60 minutes. After 55-min ischemia, an additional dosis of PTX was administered; the clip was removed for reperfusion as above. At the 60th min of reperfusion a third dosis of PTX was administered. RESULTS: PTX markedly attenuated lung injury as manifested by significant decreases (all P<0.001 as compared with the SS+IR group) of pulmonary wet/dry tissue weight ratio, total protein content, myeloperoxidase activity and tumor necrosis factor-alpha. Moreover, it was apparent that in the group PTX+I+PTX+R the improvements have been even more significant. CONCLUSION: PTX exerted a protective effect on the lung from the injuries caused by intestinal ischemia/reperfusion.

Although assist ventilation with FIO2 0.21 is the preferable mode of ventilation in the intensive care unit, sometimes controlled ventilation with hyperoxia is needed. But the impact of this setting has not been extensively studied in elderly subjects. We hypothesized that a high fraction of inspired oxygen (FiO(2)) and controlled mechanical ventilation (CMV) is associated with greater deleterious effects in old compared to adult subjects. Adult and old rats were submitted to CMV with low tidal volume (6 ml/kg) and FiO(2) 1 during 3 or 6 h. Arterial blood gas samples were measured at 0, 60 and 180 min (four groups: old and adult rats, 3 or 6 h of CMV), and additionally at 360 min (two groups: old and adult rats, 6 h of CMV). Furthermore, total protein content (TPC) and tumor necrosis factor-alpha (TNF-α) in bronchoalveolar lavage were assessed; lung tissue was used for malondialdehyde and histological analyses, and the diaphragm for measurement of contractile function. Arterial blood gas analysis showed an initial (60 min) greater PaO(2) in elderly versus adult animals; after that time, elderly animals had lowers pH and PaO(2), and greater PaCO(2). After 3 h of CMV, TPC and TNF-α levels were higher in the old compared with the adult group (P < 0.05). After 6 h of MV, malondialdehyde was significantly higher in elderly compared with the adult animals (P < 0.05). Histological analysis showed leukocyte infiltration and edema, greater in old animals. In diaphragm, twitch contraction with caffeine significantly declined after 6 h of CMV only for the elderly group. These data support the hypothesis that relatively short-term CMV with low tidal volume and hyperoxia has greatest impact in elderly rats, decreasing diaphragmatic contractile function and increasing lung inflammation.

Oliveira-Júnior IS de, Maganhin CC, Carbonel AAF, Monteiro CMR, Cavassani SS, Oliveira-Filho RM. Effects of pentoxifylline on tnf-alpha and lung histophatology in hcl-induced lung injury. Clinics. 2008;63(1):77-84. OBJECTIVE:To evaluate the effects of pentoxifylline on hydrochloric acid-induced lung lesions in rats subjected to mechanical ventilation. METHODS: Twenty male, adult Wistar-EPM-1 rats were anesthetized and randomly grouped (n=5 animals per group) as follows: control-MV (mechanical ventilation, MV group); bilateral instillation of HCl (HCl group); bilateral instillation of HCl followed by pentoxifylline (50 mg/kg bw) infusion (HCl+PTX group) and pentoxifylline infusion followed by bilateral instillation of HCl (PTX+HCl group). At 20, 30, 90 and 180 min after treatments, the blood partial pressures of CO 2 and O 2 were measured. The animals were euthanized, and bronchoalveolar lavages were taken to determine the contents of total proteins, corticosteroid and TNF-α. Samples of lung tissue were used for histomorphometric studies and determining the wet-to-dry (W/D) lung weight ratio. RESULTS: In the MV group, rats had alveolar septal congestion, and, in the HCl group, a remarkable recruitment of neutrophils and macrophages into the alveoli was noticed; these events were reduced in the animals with PTX+HCl. The partial pressure of oxygen increased in PTX+HCl animals (121±5 mmHg) as compared with the HCl (62±6 mmHg) and HCl+PTX (67±3 mmHg) groups within 30 minutes. TNF-α levels in bronchoalveolar lavage were significantly higher in the HCl group (458±50 pg/mL), reduced in the HCl+PTX group (329±45 pg/mL) and lowest in the PTX+HCl group (229±41 pg/mL). The levels of corticosteroid in bronchoalveolar lavage were significantly lower in the HCl (8±1.3 ng/mL) and HCl+PTX group (16±2 ng/mL) and were highest in the PTX+HCl (27±1.9 ng/mL). CONCLUSION: Pretreatment with PTX improves oxygenation, reduces TNF-α concentration and increases the concentration of corticosteroid in bronchoalveolar lavage upon lung lesion induced by HCl.

Purpose:To evaluate the effects of mechanical ventilation (MV) of high-oxygen concentration in pulmonary dysfunction in adult and elderly rats. Methods: Twenty-eight adult (A) and elderly (E), male rats were ventilated for 1 hour (G-AV1 and G-EV1) or for 3 hours (G-AV3 and G-EV3). A and E groups received a tidal volume of 7 mL/kg, a positive end-expiratory pressure of 5 cm H2O, respiratory rate of 70 cycles per minute, and an inspiratory fraction of oxygen of 1. We evaluated total protein content and malondialdehyde in bronchoalveolar lavages (BAL) and performed lung histomorphometrical analyses. Results: In G-EV1 animals, total protein in BAL was higher (33.0±1.9 µg/mL) compared with G-AV1 (23.0±2.0 µg/mL). Upon 180 minutes of MV, malondialdehyde levels increased in elderly (G-EV3) compared with adult (G-AV3) groups. Malondialdehyde and total proteins in BAL after 3 hours of MV were higher in elderly group than in adults. In G-EV3 group we observed alveolar septa dilatation and significative increase in neutrofiles number in relation to adult group at 60 and 180 minutes on MV. Conclusion: A higher fraction of inspired oxygen in short courses of mechanical ventilation ameliorates the parameters studied in elderly lungs.

Acute respiratory distress syndrome secondary to sepsis is associated with high morbidity and mortality. The purpose of this study was to characterize the effects of ventilatory strategy and the modulating activity of pentoxifylline in a sepsis-induced lung dysfunction model. Male Wistar rats were randomly divided into six groups, undergoing two different ventilatory strategies. Rats received live Escherichia coli or saline intraperitoneally. After 6 hours, the septic animals were treated with either pentoxifylline (25 mg/kg for 20 minutes) or normal saline infusion and ventilated with low tidal volume (6 mL/kg; septic animals with E. coli intraperitoneal [IP] infusion, PTX-treated and ventilated with low tidal volume and septic animals with E. coli IP infusion and ventilated with low tidal volume, respectively) or high tidal volume (12 mL/kg; septic animals with E. coli IP infusion, PTX-treated and ventilated with high tidal volume and septic animals with E. coli IP infusion and ventilated with high tidal volume, respectively) for 3 hours. The control animals received normal saline infusion and, after 6 hours, were ventilated with low or high tidal volume (control animals with saline infusion and ventilated with low tidal volume and control animals with saline infusion and ventilated with high tidal volume, respectively). Lung dysfunctions were assessed by wet-to-dry lung ratios, total cell count, total protein, malondialdehyde, and tumor necrosis factor-alpha concentrations in bronchoalveolar lavage (BAL). Septic animals with E. coli IP infusion and ventilated with high tidal volume presented increased wet-to-dry lung ratios, total cell count, total protein, and malondialdehyde in BAL compared with the septic animals ventilated with low tidal volume. Septic animals treated with pentoxifylline presented higher arterial oxygenation and lower cellular influx, protein leakage, malondialdehyde concentration, and tumor necrosis factor-alpha levels in BAL compared with septic animals undergoing the same ventilatory support strategies (septic animals with E. coli IP infusion and ventilated with low tidal volume and septic animals with E. coli IP infusion and ventilated with high tidal volume). Ventilatory strategy modulated the inflammatory response and pulmonary alterations in a sepsis-induced acute lung injury model, and these effects are improved by pentoxifylline.