Effect of early intervention with heparin on function of coagulopathy, liver and kidney in rats with exertional heatstroke under the ambient air of high temperature and low humidity

Abstract

To explore the effects of early intervention with heparin on function of coagulopathy, liver and kidney as well as the prognosis in rats with exertional heatstroke (EHS) under the ambient air of high temperature and low humidity. 108 healthy SPF male Sprague-Dawley (SD) rats were randomly divided into normal temperature control group, EHS + normal saline (NS) group and EHS + heparin group. Of which 54 rats were collected for survival analysis (18 rats in each group), the weight change and 8-hour survival rate were observed, and Kaplan-Meier survival curves were drawn. Other 54 rats were collected for intervention experiment, the rats in each group were subdivided into 0, 1, 2 hours subgroups according to the time points of intervention with heparin after model reproduction, with 6 rats in each subgroup. The rats were placed in an artificial experiment cabin with northwest special environment, and the temperature and the relative humidity were (25.0±1.0) centigrade and (35±5)%, respectively, in normal temperature control group, and the rats were not treated in the cabin. The rats in EHS + NS group and EHS + heparin group kept running in the cabin which temperature and relative humidity were set at (43.0±0.5) centigrade and (35±5)% until the anus temperature of rats reached 43.0 centigrade, and then the rats were placed in room temperature. The rats were injected with 1 mL/kg NS or 250 U/kg heparin sodium injection through their caudal veins at 0, 1, and 2 hours, respectively, and then the blood was collected after 1.5 hours to determine the biochemical parameters including coagulation, liver and kidney as well as platelet count (PLT). (1) The weight loss of EHS + NS group and EHS + heparin group was more significant than that of normal temperature control group (g: 8.28±1.41, 8.39±1.38 vs. 2.06±1.06, both P < 0.05), but there was no significant difference between EHS + NS group and EHS + heparin group. (2) As the time went on after modeling, serum creatinine (SCr), blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), activated partial thromboplastin time (APTT), and D-dimer of EHS rats showed a tendency of increasing, but fibrinogen (FBG), antithrombin III (AT III) and PLT were decreased gradually, which were obviously abnormal as compared with those at corresponding time point of the normal temperature control group. Heparin intervention 0 hour after modeling could improve the function of liver and kidney, FBG, D-dimer, AT III and PLT, but APTT was prolonged further. The SCr, BUN, ALT, AST and CK in EHS 2 hours + heparin group were still better than EHS + NS group [SCr (μmol/L): 93.33±7.69 vs. 110.50±13.56, BUN (mmol/L): 20.55±1.35 vs. 24.88±2.41, ALT (U/L): 322.17±36.36 vs. 492.33±64.19, AST (U/L): 1 252.33±240.86 vs. 2 725.67±461.17, CK (U/L): 1 4628.67±2 784.68 vs. 2 6843.00±2 637.16, all P < 0.01], APTT was significantly prolonged (s: 51.83±6.11 vs. 33.83±4.31, P < 0.01), and AT III and PLT were significantly increased [AT III: (78.03±9.15)% vs. (64.28±12.55)%, PLT (×109/L): 457.67±32.33 vs. 415.83±26.45, both P < 0.05], however, there was no obvious influence on FBG or D-dimer. (3) The rats in normal temperature control group were all survived within 8 hours, and all dead in EHS + NS group. The survival rate of rats given heparin intervention at 0, 1, 2 hours after successfully modeling was 50.0%, 33.3% and 0%, respectively. Kaplan-Meier survival curve analysis showed that 8-hour cumulative survival rate in EHS 0 hour, 1 hour + heparin groups was higher than that in EHS 0 hour, 1 hour + NS groups (χ12 = 7.930, P1 = 0.005; χ 22 = 4.408, P2 = 0.036), however, there was no significant difference between EHS 2 hours + heparin group and EHS 2 hours + NS group (χ 2 = 2.660, P = 0.103). Early heparin intervention can improve the coagulation function and organ function of EHS rats, while improving the survival rate of rats, indicating the earlier intervention of heparin, the better prognosis of rats is.