ABSTRACT
Objective To establish an animal model by placing one end of PICC in the hepatic portal vein of a beagle dog and leaving the other end out of its body.Methods Six Beagle dogs were given respiration anesthesia through orotracheal intubation.An incision was made through the right rectus abdominalis to locate the superior mesenteric vein (SMA) and the main hepatic portal vein.The left branch of SMA was separated and cut to put PICC into the main hepatic portal vein before being ligated and fixed.The other end of PICC was elicited through the right abdominal wall and passed beneath the skin to the back neck and fastened in case of movement.Results The anesthetic effect was good and all the operations were successful.The mean operation time was about an hour and the mean blood loss was about 15 ml.The incision healed 5-7 d after operation.Conclusion The establishment of the model can improve the effects of liver-targeting drugs,which can cut down the dosage,lower the cost of treatment and experiment and reduce the adverse effect of medicines.Through PICC,we can directly draw blood from the hepatic portal vein to measure the blood concentration before the first pass elimination.Then according to the concentration,we can calculate the absorption rate in the gastrointestinal tract,which can facilitate related experimental studies.
ABSTRACT
Objective@#To determine the scavenging effect and the change of metabolism of paraquat (PQ) using hemoperfusion (HP) once and twice within 12 hours after intoxication and explore the better scheme of HP.@*Methods@#18 beagles were randomly divided into 3 groups. Single HP group, Double HP group and Control group. Peripheral veins blood was collected at different times within 48 hours after exposure in each group. Toxin concentration was measured, analyzed and compared among 3 groups.@*Results@#6 hours after exposure, Single HP group and Double HP group has finished the first HP treatment, and the concentration of PQ was lower than that of the control group, the difference was statistically significant (P<0.05) . 10 hours after exposure, there was no statistical difference of toxin concentration among 3 groups (P>0.05) . 12 hours after exposure, Double HP group has finished the second HP treatment, the concentration of PQ was significantly lower than that of Single HP group and Control group (P<0.05) . 24 hours and 48 hours after exposure, there was no statistical difference of toxin concentration among 3 groups (P>0.05) . Statistical difference were not observed in toxicokinetical parameters among 3 groups (P>0.05) .@*Conclusion@#HP treatment once and twice within 12 hours after intoxication could effectively reduce the toxin concentration in the peripheral veins blood after HP for about 4 hours, then the toxin concentration would return to the same level as Control group quickly. It was suggested that at the beginning of poisoning, HP treatment once or twice could not significantly change the metabolism of paraquat.
ABSTRACT
Objective To study the adsorption effect of activated charcoal suspension on paraquat (PQ) in gastrointestinal tract of beagles exposed to PQ.Methods Twenty healthy male beagles were randomly divided into experimental group and control group,with 6 beagles in each group.20％ PQ solution (a dose of 30 mg/kg) was prescribed through stomach for beagles in both groups.After exposure to PQ for 30 minutes,the beagles in experimental group were given activated charcoal suspension (1.0 g/kg of type Ⅰ activated charcoal powder mixed with 100 mL of normal saline) by gavage,while the control group was only given equal volume of normal saline.After exposure to PQ for 10 minutes,30 minutes,and 1,2,4,8,12,24,and 48 hours,blood was collected from hepatic portal veins and peripheral veins to detect the PQ concentration change in the plasma.The toxicokinetics software DAS 2.1.1 was applied to analyze PQ concentration and compare the change in toxicokinetics parameters between the both groups.The change in vital signs including heart rate (HR),respiratory rate (RR) and pulse oxygen saturation (SpO2) was dynamically monitored 10 minutes before exposure,4 hours and each day from the 1st to the 7th day after exposure.Results After exposure to PQ,the poison concentration in the plasma of hepatic portal veins and peripheral veins in the control group rose quickly and reached peak 4 hours later.It fell quickly at first,and fell slowly 8 hours later.But in the experimental group,the increase rate to the peak was significantly slow.Besides,PQ peak fell more obviously than that in the control group and it was about 50％ of the control group (μg/L:123.50 ± 11.67 vs.255.18 ± 12.29 in blood from hepatic portal veins,122.35± 11.72 vs.250.86± 11.15 in blood from peripheral veins).After 8 hours it fell much more quickly than that of the control group.After exposure to PQ for 48 hours,PQ concentration in the plasma was still lower than that of the control group (μg/L:0.53 ± 0.18 vs.15.98 ± 5.58 in blood from hepatic portal veins,0.31 ± 0.01 vs.15.03 ± 4.82 in blood from peripheral veins,both P ＜ 0.01).With the toxicokinetics analysis,compared with the control group,the maximum concentration (Cmax) and area under the curve (AUC) of PQ in the plasma of hepatic portal veins and peripheral veins in the experimental group were significantly decreased [Cmax (μg/L):125.07 ± 9.49 vs.255.18 ± 12.29 in blood from hepatic portal veins,123.38 ± 9.52 vs.250.86 ± 11.15 in blood from peripheral veins;AUC (mg· L-1· h-1):1.6±0.2vs.3.3 ± 0.4 in blood from hepatic portal veins,1.5 ± 0.2 vs.3.2 ± 0.3 in blood from peripheral veins],time to the peak (Tmax) of PQ was slowed (hours:5.3 ± 1.9 vs.4.0 ± 0.0 in blood from hepatic portal veins,4.7 ± 1.5 vs.4.0 ± 0.0 in blood from peripheral veins),and PQ plasma half-life (t1/2) and mean retention time (MRT) were significantly shortened [t1/2 (hours):3.8 ± 1.2 vs.15.4± 3.7 in blood from hepatic portal veins,3.5 ± 1.0 vs.15.5 ± 2.7 in blood from peripheral veins;MRT (hours):8.0± 1.5 vs.13.4± 1.2 in blood from hepatic portal veins,7.6± 1.3 vs.13.3± 1.2 in blood from peripheral veins;all P ＜ 0.01].After exposure to PQ,HR and RR in both the experimental group and the control group increased and reached to the peak about the 4th day and then the increase rate began to slow down gradually;SpO2slowed down gradually and reached to the valley about the 4th day and then it began to recover,but the change range of vital signs in the experimental group was smaller than that of the control group,and the parameters were significantly better than those of control group [4-day HR (bpm):134.50±3.00 vs.142.00±6.43,4-day RR (times/min):31.00±0.58 vs.34.33±0.94,4-day SpO2:0.900±0.006 vs.0.873±0.005,all P ＜ 0.05].Conclusion Activated charcoal administrated at 30 minutes after PQ poisoning can slow down the increase rate of PQ concentration in the plasma,decrease the peak concentration and has less influence on vital signs in beagles.