小型猪冠状动脉再狭窄模型中普通肝素用量的探讨

The dose investigation of unfractionated heparin in minipig model for coronary artery restenosis

目的:评价低、中度肝素化在小型猪冠状动脉再狭窄模型中的应用效果,探讨该模型合理的普通肝素用量。方法:根据普通肝素用量将24只健康小型猪随机分为低度肝素化组(100U/kg)和中度肝素化组(150U/kg)。分别测定基础活化凝血时间(activating clotting time,ACT)值和静脉注射肝素后不同时间点ACT值。比较2组的抗凝效果,术后压迫止血情况及术中、术后24h的安全性。结果:中度肝素化组和低度肝素化组在静脉推注普通肝素后5minACT达到峰值〔(315.1±50.85)svs(276.2±59.38)s,P=0.110〕,20min时2组均维持较高ACT值,但中度肝素化组明显高于低度肝素化组〔(284.8±45.14)svs(206.3±32.44)s,P=0.003〕。60min时中度肝素化组仍维持较高的ACT值(193.9±21.87)s,而低度肝素化组ACT值明显回落(132.2±13.30)s,与前者相比差异有统计学意义(P<0.001)。中度肝素化组术后徒手压迫止血时间显著长于低度肝素化组有〔(17.3±2.06)minvs(13.5±2.94)min,P=0.006〕。总体手术平均时间为(13.2±2.34)min。2组术中和术后24h均未发生冠状动脉事件。结论:在小型猪冠状动脉再狭窄模型中,若手术时间控制在20min内,则低度肝素化(100U/kg)既可保证手术的安全性又可缩短压迫止血时间。

Backgroun：Currently,the investigation of new drug eluting stent is paid more attention.The use of the juvenile Chinese experimental mini-pigs model for coronary artery restenosis is increasing.In the past,The procedure needed under general anesthesia and tracheal cannula.We had to do femoral artery arteriotomy to creat the femoral approach.The time was long and the dose of unfractionated heparin in the model was high（about 200 U/kg） so as to keep a appropriate anticoagulation effect.As a result,the incidence of hemorrhage and the mortality is both high.Objective：To evaluate the effects of different dose unfractionated heparin in minipig model for coronary artery restenosis and search the suitable dose for the model.Methods：All animals were treated with clopidogrel（25 mg） and aspirin（500mg） for 2 days prior to the procedure and then daily throughout the study period.A total of twenty-four juvenile Chinese experimental mini-pigs（23.1 ± 4.4 kg） of female gender were allocated into two groups-low heparinization group（100 U/kg）and midrange heparinization group（150 U/kg）-according to the dose of unfractionated heparin in randomization.Under general anesthesia,the swine received the placement of 6 Fr introducer sheath into the porcine femoral arteries by a modified Seldinger technique.Take the samples of blood before intravenous injection of unfractionated heparin as Foundation.Through the femoral approach,6 Fr Judkins right 4 catheters were used for both left main and right ostia.After coronary angiography,each animal underwent placement of stents in coronary arteries.72 stents were being placed in the left anterior descending,circumflex and right coronary artery in the same animals.The guiding catheter was used as a reference to obtain a 1.1：1 to 1.2：1 stent/artery ratio compared with the baseline vessel diameter.Meanwhile take the samples on the point of 5 minutes,20 minutes,30 minutes and 60 minutes,and determine the activated clotting time.The effects of unfractionated heparin were analyzed with statistical methods.Results：Both low heparinization group and midrange heparinization group can achieve the target ACT value on the point of 5 minute〔（315.1 ± 50.85）s vs（276.2 ± 59.38）s,P = 0.110〕and keep the target ACT in 20 minutes.But The ACT value of midrange heparinization group is longer than low heparinization group on the point of 20 minutes,30 minutes and 60 minutes〔（284.8 ± 45.14）s vs（206.3 ± 32.44）s,P = 0.003〕;〔（252.1 ± 38.50） vs（189.3 ± 29.82）,P = 0.006〕;〔（193.9 ± 21.87）s vs（132.2 ± 13.30）s,P = 0.0005〕.However the time for compress hemostasis is elongated too〔（17.3 ± 2.06）min vs（13.5 ± 2.94）min,P = 0.006〕.The safety of the two grops is similar.Conclusion：Our data demonstrates that low heparinization can provid the safty of operation and reduce the time for compress hemostasis,if we can complete the operation in 20 minutes.