| Objective: With the rapid development of society, there are a lot of vascular injuries of extremity in clinical. In the procedure to save the limb, vascular anastomosis is the most important part. However, vascular spasm is a common and serious complication during vascular anastomosis operation, which occured mostly within 48 hours after operation reported from the literature. It usually presents a strong vascular contraction, and can sustain from a few minutes to several hours , the length of vascular spasm varies from local part to a longer one. If not handled properly, blood vessels spasm could result in a series of pathological changes, such as the vascular intima shedding and thrombosis, tissue is chemia-hypoxia and even necrosis. Currently the treatment methods in clinical includes: (1)Elevate the injuried limb, massage, remove compression bandaging or skin dressing in order to decompression and so on.(2)Heat, relieve pain, local anesthesia, vasodilator drugs, intravenous heparin and other methods. Although these mehods have no obvious trauma, their effect are uncertain for many patients. If the clinical application of these methods have no effect, exploratory surgery is needed immediately, but sometimes surgical exploration itself cannot resolved all the problems such as intractable vasospasm, no-reflow phenomenon, and so on, in this condition the operation only increases the suffering of patients. If postoperative medication can prevent or mitigate the vascular crisis, it will be of great significance.Papaverine is a morphine-type, non-specific relieving spasm drugs. It could relieve vascular smooth muscle spasm and pain during 4 ~ 6h. Intraoperative application of papaverine wet packing can completely relax blood vessels to relieve vasospasm effectively. Intravenous injection or intramuscular injection in accordance with body weight of papaverine for vasospasm has a better results.There are vomiting, nausea, headache and other side effects, after systemic application of papaverine. Used with a long time, it is easy to get addiction and has toxic effects on the liver. There are some studies about local application of papaverine, which are mainly focused on the comparison of postoperative local and systemic medication. Wang Peiji gave papaverine and lidocaine to the tiny blood vessels anastomosis by the use of PCA pump. He found it was effective in preventing and treatment of vascular spasm, but there were a few literatures on the effects of local dose, so it will be very useful to determine the local minimum papaverine effective dose range of drugs, and it will provide experimental data for clinical intervention and prevention of vascular spasm through papaverine.Methods: 1 Experimental animal groups: 48 New Zealand white rabbits(2.5-3.0 kg, 5 months old, Hebei Medical University animal experiment center)were randomly divided into four groups. Each group had 12 rabbits. The animals of Group received normal saline as a control group, while the animals of group B were given papaverine in accordance with 1.5 mg / kg dose. The doses of Papaverine given to Group C and Group D were 3.0 mg/kg and 4.5 mg/kg respectively.2 Vascular anastomosis model and drug treatment: Each animal was given 30mg/kg pentobarbital anesthesia through line ear vein injection. The other procrdures were done as follow: The left groin and thigh hair removal, routine disinfection, sterile shop towels, the surgical exposure of the left femoral artery, then cut off the femoral artery in the point which was 2cm away from the distal bifurcation of the artery itself, gave anastomosis with 10-0 non-invasive suture, placed an epidural catheter(inner diameter 1 mm)on the anastomosis of the femoral artery, whose end was fixed to the infusion pump in vitro through the skin, stopped bleeding, sew up the wound layer by layer after saline washing, figured out the papaverine amount through per kilogram of body weight, diluted it with normal saline to 24ml, and gave it to the animal at the infusion rate of 1 mL / h by using infusion pump. 3 The animals were fed in normal diet after the operation, 4 animals were chosen randomly from each group after 6 hours of the operation, they were given the same anesthesia as done before, then each animal received ultrasound measurement of bilateral femoral, the results of RI(resistance index), PI(pulse index)were recorded, endothelin(ET), nitric oxide(NO) concentration were detected after separation of serum which was got from the heart blood sample.SPSS13.0 statistical package was used for data analysis, data were presented in mean±standard deviation(±s), single-factor analysis of variance was used for the comparision between the groups, the SNK test was used for, all reported P value are two sided(with values less than 0.05 considered to indicate statistically significance).Results:1 General conditions: The 48 experimental animals had good spirits, normal eating habit, good range of activities, there were no infection of the incision no rupture of the anastomosis, no loosening, extrusion, blocking of the indwelling tube.2 Hemodynamic indices: RI(resistance index), PI(pulse index): The resistance indices RI and PI got 6 hours after the operation: There were statistically significant(P<0.05)between Group A(0.74±0.02, 1.81±0.11), B group(0.72±0.03, 1.75±0.07) and group C(0.62±0.04, 1.48±0.10), group D(0.61±0.06,1.50±0.08). The resistance indice RI got 12 hours after the operation: There were no statistically significant (P >0.05) between all the groups the resistance indice PI got 12 hours after the operation: There were statistically significant(P <0.05) between group A(1.81±0.11), group B (1.75±0.07) and group C(1.48±0.10), group D(1.50±0.08). The resistance indices RI and PI got 24 hours after the operation: There were statistically significant(P <0.05) between group A(0.70±0.08, 1.75±0.10), group B(0.69±0.06, 1.56±0.08) and group C(0.56±0.06, 1.35±0.12 ), group D(0.55±0.08, 1.36±0.07), but there also was statistically significant (P <0.05)between group A(1.75±0.10) and group B(1.56±0.08) in the datd analysis of PI. 3 Blood endothelin concentration(ETC, pg/ml), nitric oxide concentration (NOC, uM/L): The ETC got 6hours, 12hours, 24hours after the operation in group C(99.33±6.61, 116.38±7.47, 94.91±7.25) and group D(101.44±7.45, 114.67±7.04, 99.09±7.40) were all less than those of group A (131.85±9.61, 143.03±8.53, 127.57±6.79) and group B(120.16±14.67, 137.07±8.33, 111.29±10.04) respectively, there was statistically significant (P <0.05). The NOC got 6 hours, 12 hours, 24 hours after the operation in group C(259.7±10.1, 384.1±31.4, 325.5±55.1) and group D(270.3±15.1, 361.2±61.9, 370.7±48.7) were all all less than those of group A(148.7±8.2, 157.5±13.8, 182.3±34.9) and group B(159.7±8.1, 180.8±24.5, 252.6±22.3) respectively, there was statistically significant(P<0.05). There also was statistically significant(P <0.05) in the NOC got 24hours after the operation between group A(182.3±34.9) and group B(252.6±22.3).Conclusions: Topical application of papaverine whose concentration was 3.0mg/kg or 4.5mg/kg could effectively alleviate vascular spasm after anastomosis, have good effect on vascular anastomosis patency, prevent the occurrence of vascular crisis and minimize the complications of systemic medication as much as possible. The results of this study could provide valuable reference for the practise of clinical medicine. |
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