INTRODUCTION: Mechanical ventilation with positive end expiratory pressure (PEEP) improves oxygenation and treats acute pulmonary failure. However, increased intrathoracic pressure may cause regional blood flow alterations that may contribute to mesenteric ischemia and gastrointestinal failure. We investigated the effects of different PEEP levels on mesenteric leukocyte-endothelial interactions. METHODS: Forty-four male Wistar rats were initially anesthetized (Pentobarbital I.P. 50mg/kg) and randomly assigned to one of the following groups: 1) NAIVE (only anesthesia; n=9), 2) PEEP 0 (PEEP of 0 cmH2O, n=13), 3) PEEP 5 (PEEP of 5 cmH2O, n=12), and 4) PEEP 10 (PEEP of 10 cmH2O, n=13). Positive end expiratory pressure groups were tracheostomized and mechanically ventilated with a tidal volume of 10 mL/kg, respiratory rate of 70 rpm, and inspired oxygen fraction of 1. Animals were maintained under isoflurane anesthesia. After two hours, laparotomy was performed, and leukocyte-endothelial interactions were evaluated by intravital microscopy. RESULTS: No significant changes were observed in mean arterial blood pressure among groups during the study. Tracheal peak pressure was smaller in PEEP 5 compared with PEEP 0 and PEEP 10 groups (11, 15, and 16 cmH2O, respectively; p<0.05). After two hours of MV, there were no differences among NAIVE, PEEP 0 and PEEP 5 groups in the number of rollers (118±9,127±14 and 147±26 cells/10minutes, respectively), adherent leukocytes (3±1,3±1 and 4±2 cells/100µm venule length, respectively), and migrated leukocytes (2±1,2±1 and 2±1 cells/5,000µm², respectively) at the mesentery. However, the PEEP 10 group exhibited an increase in the number of rolling, adherent and migrated leukocytes (188±15 cells / 10 min, 8±1 cells / 100 µm and 12±1 cells / 5,000 µm², respectively; p<0.05). CONCLUSIONS: High intrathoracic pressure was harmful to mesenteric microcirculation in the experimental model of rats with normal lungs and stable systemic blood pressure, a finding that may have relevance for complications related to mechanical ventilation.

A gravidade dos efeitos causados pela exposição ambiental e ocupacional ao benzeno determinou o controle de sua utilização. No entanto, mesmo nestas condições, toxicidade ao sistema imune e nervoso tem sido descrita. A toxicidade do benzeno é determinada pelos seus produtos de biotransformação, em que fenol (FE) e hidroquinona (HQ) têm papel relevante na imunotoxicidade. Neste contexto, o presente trabalho mostra que a exposição de ratos Wistar, machos, a doses de 5 ou 10 mg/kg de HQ (via i.p., uma vez ao dia, 13 doses consecutivas, com intervalos de 2 dias a cada 5 doses) provocou reduções acentuadas no influxo de leucócitos polimorfonucleares (PMN) e mononucleares (MN) para o pulmão 24 horas após inalação de Lipopolissacarídeo (LPS) de Salmonella abortus. Diferentemente, a migração de leucócitos em animais expostos ao FE não foi alterada. A exposição a ambos os agentes químicos simultaneamente (dose de 5 mg/kg cada) manteve a redução na migração de MN detectada em animais expostos à HQ e potencializou o efeito inibitório da HQ sobre a migração de leucócitos PMN. Os prejuízos nas migrações de leucócitos não foram decorrentes de modificações no número destas células na circulação. É importante ressaltar que os efeitos foram induzidos por doses dos agentes químicos que não causaram prejuízo à função hepática ou renal, determinados pela atividade das transaminases hepáticas e a concentração de creatinina no soro. Em conjunto, os dados obtidos mostram a exposição a baixas doses de HQ não provoca alterações nos parâmetros empregados como indicadores de toxicidade. No entanto, os efeitos tóxicos são manifestados resposta do organismo ao trauma.

The high toxicity induced by occupational and environmental benzene exposure lead to its use restriction. However, at these conditions, neuronal and immune toxicity has been described. It is well known that benzene metabolites, such as hydroxyl compounds phenol (PHE) and hydroquinone (HQ), are responsible for immunotoxicity. In this context, it has shown herein that male Wistar rats exposed to HQ (doses of 5 or 10 mg/kg/day; 13 days with 2-day intervals every 5 doses) presented marked reduction in the number of mononuclear (MN) and polymorphonuclear (PMN) leukocytes in the bronchoalveolar fluid 24 hours after inhalation of Lipopolyssacaride of Salmonella abortus (LPS; 100 µg/mL). On the other hand, leukocyte migration into inflamed lungs was not altered in FE exposed rats, since values obtained were similar to those detected in control animals. Simultaneous exposure to HQ and PHE (5 mg/kg each compound) maintained the decreased number of MN cells observed in HQ exposed rats and potentiated the reduction of PMN cells induced by HQ exposure. The impaired leukocyte migration into inflamed lung did not reflect alterations on number of circulating cells. Moreover, it is important to emphasize that schedule of intoxication did not alter the functional ability of liver and kidney, as detected by normal activity of transaminases and creatinine concentration in the serum. Therefore, it is shown herein that in vivo exposures to lower doses of HQ do not alter end points used as biological indicators of toxicity, nevertheless toxic effects are evident after a host defense.