Objective To observe the effects of penehyclidine hydrochloride ( PHCD) combined with mechanical ventilation ( MV) on inflammatory response in rats with ARDS induced by oleic acid ( OA) .Methods The rat ARDS model was established by OA via intravenous injection ( iv) . 32 adult healthy male SD rats were randomly divided into four groups, ie. a normal control group( group C: intra-peritoneal injection of a same amount of normal saline and intravenous injection of a same amount of normal saline respectively rather than PHCD) , a model group( group A1) , a PHCD group ( group A2: intra-peritoneal injection of 0. 5 mg/kg PHCD30 minutes before OA iv) and a PHCD+MV group ( group A3: VT = 4 mL/kg,respiratory rate =70 beats /min, I∶E =1∶2, FiO2 =21%) . Four hours after OA iv, arterial partial pressure of oxygen ( PaO2 ) was measured, and the oxygenation index ( PaO2 /FiO2 ) as well as wet /dry weight ratio( W/D) of lung tissue were calculated respectively. The pathological changes of lung tissue was observed through light microspcope. Interlukin-8 ( IL-8 ) , myeloperoxidase ( MPO) and NF-κB in lung tissue homogenate were measured by enzyme linked immunosorbent assay ( ELISA ) . Results Extensive pneumonedema, pneumorrhagia, focal atelectasis and amout of inflammatory cells infiltration in lung tissues were all revealed in ARDS rats. Lung injury score ( 8. 63 ±2. 20 vs. 1. 38 ±0. 92) , W/D ratio ( 8. 37 ±0. 99 vs. 4. 08 ±0. 65) were all higher in the ARDS rats than those in group C( all P lt;0. 01) . PaO2 /FiO2 was lower in group A1 than that in group C [ ( 206 ±32) mm Hg vs. ( 428 ±28) mm Hg, P lt; 0. 01] . The concentrations of MPO [ ( 33. 91 ±1. 43) ng/mL vs. ( 20. 92 ±1. 40) ng/mL) ] , IL-8 [ ( 809 ±39) ng/L vs. ( 583 ±91) ng/L] and NF-κB [ ( 1163 ±105) ng/L vs. ( 803 ±130) ng/L] in lung tissue homogenate were significantly increased in the ARDS rats than those in group C ( all P lt;0. 01) . Pathological changes of lung tissue ( including pneumonedema, pneumorrhagia, atelectasis and inflammatory cell infiltration, etc. )obviously improved when treated by PHCD or/and PHCD combined with MV ( all P lt;0. 05) . PaO2 /FiO2 in group A2 and A3 were both significantly increased when compared with group A1 ( both P lt; 0. 05) .Meanwhile,W/D ratio, lung injury score, and concentrations of MOP, IL-8 and NF-κB were sharply decreased in group A2 and A3 ( all P lt;0. 05) . The improvement in all above indices were more significant in group A3 than those in group A2, despite all those indices failed to meet the levels of normal rats ( all P lt; 0. 05) .Conclusion PHCD can inhibit the inflammatory response in ARDS rats induced by OA iv, through which it protect the lung tissue frominjury induced by OA. The protective role of PHCD plus MV is superior to that of PHCD only.
Objective To observe whether additional penehycl idine hydrochloride (PHC) in mechanical ventilation produces therapeutic effect on oleic acid (OA) induced acute lung injury (ALI) in canine. Methods Seventeen male canines (weighing 12-17 kg) were divided into control group (n=5), OA group (n=6) and PHC group (n=6). ALI model was developed by central venous injection of OA in canines of OA and PHC groups. ALI model was kept steady in air, all groups received mechanical ventilation 90 minutes later. Three groups received normal sal ine 0.25 mg/kg without injection of OA(control group), normal sal ine 0.25 mg/kg after injection of OA (OA group) and PHC 0.25 mg/kg after injection of OA (PHCgroup) respectively at 0 h (90 minutes after onset time of ALI/ARDS). The heart rate (HR), mean arteial pressure (MAP), mean pulmonary arterial pressure (MPAP), central venous pressure (CVP), pulmonary artery wedge pressure (PAWP), artery blood gas analysis, cardiac output (CO), extravascular lung water index (EVLWI), FiO2 and VT were observed respectively at basel ine, onset time of ALI/ARDS and 0 h, then again at 1 hour intervals for 6 hours. Besides the above, airway peak pressure (Ppeak), airway plat pressure (Pplat), mean airway pressure (Pmean) and positve end-expriatory pressure (Peep) were also observed each hour during 1-6 hours. Oxygenation index (OI), pulmonary vascular resistance (PVR), systemic vascular resistance (SVR), alveolar-arterial differences for O2 (AaDO2) and dynamic lung compl iance (DLC) were calculated and pulmonary tissue was collected for histopathologic investigation and dry wet weight ratio (WDR) test. Results The functional parameters of PHC group were improved when compared those of OA group, but there was no siginficant difference; WDR of independent region of three groups were 80.42% ± 3.48%, 82.67% ± 4.01% and 82.26% ± 1.43% respectively; WDR of dependent region of three groups were 80.51% ± 3.60%, 83.71% ± 1.98% and 82.57% ± 1.08% respectively. WDR of PHC group were obviously improved when compared with those of OA group, but there was no significant difference. Independent and dependent regions of PHC group were significantly improved when compared those of OA group in histopathologic scores, alveolar edema, inflammatory infiltration and over-distension (P lt; 0.01). Conclusion Additional PHC in mechanical ventilation produces obvious therapeutic effect on OA induced acute lung injury in canine.
