Effects of mechanical ventilation with different tidal volumes on coagulation/fibrinolysis in rabbits with acute respiratory distress syndrome

Abstract

To observe the effects of mechanical ventilation with different tidal volumes (VT) on coagulability and fibrinolytic characteristics in rabbits with acute respiratory distress syndrome (ARDS) induced by two-hits with oleic acid (OA) and lipopolysaccharide (LPS). Forty healthy adult male rabbits were randomly divided into five groups (8 rabbits in each group): sham operation group, model group, low VT group (6 mL/kg), rontine VT group (10 mL/kg ), high VT group (15 mL/kg). ARDS model was reproduced by sequential injection of 0.1 mL/kg OA and 500 μg/kg LPS via auricular vein, and the rabbits in sham operation group received normal saline in same volume. Mechanical ventilation was performed in different VT groups after model reproduction, and the end of the experiment was determined as 6 hours after LPS injection. Blood was collected from the carotid artery at 30 minutes and 360 minutes after LPS injection, with which arterial partial pressure of oxygen (PaO2) was determined, and oxygenation index was calculated. Internal jugular vein blood was collected at 5, 120, 240, and 360 minutes after LPS injection, and activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (Fib) and antithrombin III (AT-III) were determined. The blood was collected at the end of the experiment, and then the rabbits were sacrificed, and serum levels of procollagen type III (PIIIP), plasminogen activator inhibitor-1 (PAI-1) as well as PIIIP level in lung tissue were determined. The wet/dry weight ratio (W/D) of lung tissues was calculated. Compared with sham operation group, oxygenation index at both 30 minutes and 360 minutes were significantly decreased in model group, while W/D ratio was significantly increased. PT and APTT at 5 minutes were significantly shortened followed by a gradual increase. Fib and AT-III showed no change at 5 minutes followed by a gradual decrease, while serum PAI-1 and PIIIP as well as PIIIP in lung tissue were significantly increased. There was no significant difference in oxygenation index between all VT groups and model group, with a tendency to increase in low VT group. W/D ratio in low VT group was the lowest (5.09±0.19), and it was significantly lower than that of the model group (6.02±0.27, P<0.01), while it was the highest in high VT group (6.27±0.32). PT and APTT in all VT groups were gradually prolonged, and Fib and AT-III were gradually decreased. PT and APTT in low VT group were significantly shorter than those in model group from 120 minutes on [PT (s): 120 minutes: 8.90±0.28 vs. 11.43±0.28, 240 minutes: 9.18±0.21 vs. 11.99±0.50, 360 minutes: 9.25±0.15 vs. 12.49±0.29; APTT (s): 120 minutes: 69.09±3.91 vs. 76.08±4.21, 240 minutes: 67.53±2.14 vs. 79.71±2.25, 360 minutes: 66.95±1.13 vs. 83.21±4.01, all P<0.05], Fib (g/L) was significantly elevated (120 minutes: 3.80±0.09 vs. 3.38±0.15, 240 minutes: 3.91±0.05 vs. 2.47±0.16, 360 minutes: 4.06±0.13 vs. 2.39±0.16, all P<0.05), and no significant difference was found in AT-III. Serum contents of PAI-1 and PIIIP as well as PIIIP in lung tissue were significantly lowered [ serum PAI-1 (ng/L): 1.14±0.26 vs. 1.63±0.91, serum PIIIP (ng/L): 1.62±0.52 vs. 2.91±0.64, lung PIIIP (ng/L): 4.40±0.58 vs. 5.75±0.47, all P<0.01]. The change tendency of all parameters in routine VT group was lower than that in low VT group, PT at 120 minutes and 360 minutes, APTT at 240 minutes and 360 minutes was significantly shorter than that in model group, and Fib at 120 minutes and 240 minutes were significantly higher than those in model group (all P<0.05). No significant difference was found in AT-III, serum PAI-1 and PIIIP as well as lung PIIIP as compared with model group. PT and APTT at 360 minutes in high VT group were significantly longer than those in model group, Fib at 360 minutes was significantly lower than that in model group, and lung PIIIP was significantly higher than that in model group. There are some important changes in coagulability which changes from a hyper state into a hypo coagulate state, while fibrinolysis is inhibited during the pathological process of ARDS produced by two-hit of OA and LPS. Mechanical ventilation with low VT can obviously improve coagulability and fibrinolytic status, while ventilation with routine VT has little effect on coagulability and fibrinolytic status. Mechanical ventilation with high VT, however, will greatly deteriorate the coagulability and fibrinolytic function in ARDS.