Effects of low molecular heparin combined with dexamethasone on coagulation and fibrinolysis at early stage in rats with acute respiratory distress syndrome / 中国中西医结合急救杂志

ABSTRACT

Objective To observe the effects of low molecular weight heparin (LMWH) combined with dexamethasone (Dex) on coagulation and fibrinolysis at the early stage in rats with acute respiratory distress syndrome (ARDS) induced by two-hit of oleic acid (OA) and lipopolysaccharide (LPS).Methods Forty healthy adult male Sprague-Dawley (SD) rats were randomly divided into sham operation, ARDS model, Dex, LMWH and combining therapy groups (8 rats in each group). The rat ARDS model was established by sequential two-hit with intravenous injection of OA 0.2 mL/kg in a tail vein and intra-peritoneal injection of LPS 5 mg/kg. After model establishment, the rats in Dex group were intra-peritoneally injected with 10 mg/kg Dex, and those in LMWH group were intravenously injected with 200 U/kg LMWH, while the rats in combining therapy group were given Dex and LMWH simultaneously with the same dosages and methods as above mentioned respectively. In sham operation group, however, the rats were intravenously injected with 0.4 mL of normal saline (NS) and were given 2 mL/kg of intra-peritoneal NS injection, and they accepted another 1 mL/kg NS intra-peritoneal injection 4 hours later, the other procedures being the same as those in the model group. The experiment was ended at 6 hours after the establishment of ARDS model. A light microscope was used to observe the pathological changes in lung tissues, partial pressure of arterial blood oxygen (PaO2) was measured, and the oxygenation index (PaO2/FiO2) was calculated. Wet to dry weight (W/D) ratio of lung tissues was also checked. Coagulation indexes were measured by solidification method, and the serum level of plasminogen activator inhibitor-1 (PAI-1) as well as the content of procollagen type Ⅲ (PC-Ⅲ) was determined by enzyme linked immunosorbent assay (ELISA).Results Under the light microscope, effusion of red blood cells, fibrin deposit in the lung interstitium and alveoli, formation of transparent membrane at alveolar wall, inflammatory cells infiltration in pulmonary interstitial tissue, and fibrinous thrombi in lung capillaries or lung arterioles were seen in the model group. Compared with model group, the red blood cells effusion and fibrin deposition in the lung interstitium and alveoli were less, inflammatory cells infiltration in pulmonary interstitium was alleviated and the fibrinous blood emboli in the lung capillaries or lung small arterioles were also decreased in Dex, LMWH and combining therapy groups, among the three groups, the best results being in the combining therapy group. Compared with sham operation group, the PaO2/FiO2 was significantly lowered [mmHg (1 mmHg = 0.133 kPa) 272.02±28.28 vs. 420.24±35.52,P < 0.01], the lung W/D ratio was obviously higher (5.59±0.40 vs. 3.82±0.28,P < 0.01), prothrombin time (PT) as well as thrombin time (TT) were markedly longer [PT (s) 18.78±1.57 vs. 16.36±0.97, TT (s) 39.02±5.03 vs. 29.22±8.83, bothP < 0.05], fibrinogen (Fib) content was significantly decreased (g/L 1.82±0.26 vs. 2.69±0.40,P < 0.01), but both the serum contents of PAI-1 and PC-Ⅲ were remarkably elevated in model rats [PAI-1 (ng/L) 719.04±103.74 vs. 517.25±119.18, PC-Ⅲ (μg/L) 29.93±3.24 vs. 22.97±6.26, bothP < 0.01); Compared with model group, the level of PaO2/FiO2 was significantly elevated, and the lung W/D ratio was obviously decreased in Dex, LMWH and combining therapy groups respectively, the most significant changes being in combining therapy group [PaO2/FiO2 (mmHg) 376.78±25.25 vs. 272.02±28.28, lung W/D ratio 4.14±0.42 vs. 5.59±0.4, bothP < 0.01] , in LMWH group, the prolongation of TT was the longest (s 52.00±4.24 vs. 39.02±5.03,P < 0.05), while Fib contents in the three treatment groups were all obviously increased (g/L 2.37±0.38, 2.59±0.51, 2.59±0.24 vs. 1.82±0.26,P < 0.05 orP < 0.01); meanwhile, the decrease of PAI-1 in combining therapy group was the greatest (ng/L 546.02±93.94 vs. 719.04±103.74,P < 0.01). The indexes showed no statistically significant differences among the three treatment groups, except that PT in combining therapy group which was significantly longer than that in Dex and LMWH groups (s 19.98±1.61 vs. 17.20±1.48, 17.02±2.34, bothP < 0.05). Conclusions The rats with ARDS induced by two-hit of OA combined with LPS have coagulation dysfunction and fibrinolytic inhibition. Using LMWH early can improve coagulation and fibrinolytic status in the rats with ARDS, and the therapeutic effects of LMWH plus Dex for treatment of ARDS are better than those of using each of them alone.