Serum and lung endothelin-1 increased in a canine model of ventilator-induced lung injury

Background Nitric oxide (NO) plays an important role in acute lung injury (ALI), acute respiratory distress syndrome(ARDS), and in ventilator-induced lung injury (VILI). A change in the balance of endothelin-1 (ET-1) and NO in theALI/ARDS can also add to these problems. However, the profile of ET-1 and the balance of ET-1 and NO are stillunknown in a VILI model.Methods Models of oleic acid induced ALI were established in dogs; these models were then randomized into threegroups undergone different tidal volume (VT) mechanical ventilation, which included a VT6 group (VT equaled to 6 ml/kgbody weight, positive end expiratory pressure (PEEP) equaled to 10 cmHO, n=6), a VT10 group (VT equaled to 10 ml/kgbody weight, PEEP equaled to 10 cmHO, n=4) and a VT20 group (VT equaled to 20 ml/kg body weight, PEEP equaledto 10 cmHO, n=6) for 6-hour ventilation. The levels of ET-1 and NO in serum and tissue homogenates of lung wereobserved throughout the trial.Results PaOwas increased after mechanical ventilation, but hypercapnia occurred in the VT6 group. The magnitudesof lung injury in the VT20 group were more severe than those in the VT6 group and the VT10 group. Serum levels of ET-1and NO increased after ALI models were established and slightly decreased after a 6-hour ventilation in both the VT6group and the VT20 group. The serum ET-1 level in the VT20 group was higher than that in the VT6 group and the VT10group after the 6-hour ventilation (P <0.05) while the serum NO levels were similar in the three groups (all P >0.05).There was no significant difference in serum ratio of ET-1/NO between any two out of three groups (P >0.05), althoughthere was a significant positive relationship between serum ET-1 and serum NO (r=0.80, P<0.01). The levels of ET-1 andNO in the lung were increased after ventilation. The lung ET-1 level in the VT20 group was significantly higher than that inthe VT6 group and VT10 group (both P <0.05) while there was no significant difference in lung NO levels between twogroups (P>0.05). In the lung tissue, the ratio of ET-1/NO was significantly higher in the VT20 group than in the VT6 groupand VT10 group after the 6-hour ventilation (P<0.05) as there was a significant positive relationship between ET-1 andNO in the lung (r=0.54, P<0.05).Conclusions The production of ET-1 and NO was increased in serum and lung tissue in a VILI model. But the ET-1levels increased much more than the NO levels in the lung, though there was a significant positive relationship betweenlevels of ET-1 and NO. These results showed that there was an interaction between ET-1 and NO in a VILI model andchanging the balance of ET-1 and NO levels might contribute to the pathophysiologic process of VILI.