【作者】 陈庆亮；

【导师】 王钢；

【作者基本信息】 南方医科大学 ， 骨外科学， 2008， 硕士

【摘要】 背景:随着显微外科的发展,皮瓣移植成为修复创伤组织缺损最有效的方法。皮瓣移植的血管口径一般在1～3mm间,这些血管在组织上有明显的肌层,对各种物理化学刺激具有高度敏感性,所以吻合口及附近的一段血管极易发生痉挛,是显微外科手术中和手术后的常见并发症。严重持久的血管痉挛导致移植组织缺血缺氧甚至坏死,导致手术失败。临床上在显微外科皮瓣移植术后,常用罂粟碱等血管舒张药预防和解除血管痉挛,增加皮瓣循环血流量,使皮瓣存活能力明显增强。给药途径主要有:(1)采用一日多次,连续数日臀部肌肉注射;(2)24小时连续静脉注射。虽然临床效果较好,但这两种方法仍存在着不同程度的缺陷。如果静脉注射药物速度掌握不好、剂量过大,易导致心律失常、血压下降等到严重不良反应,加重组织缺血缺氧;而臀部肌肉注射如果剂量过大,将导致病人难于耐受,剂量过小则解痉效果差。而且有研究表明罂粟碱30～60 mg肌注或静脉注射后经过吸收和分布,作用于远端的药物浓度甚微,经计算到达手指仅有几微克。但皮瓣局部应用扩血管药物尚未常规采用,且效果如何?目前国内尚无对皮瓣近距离注射血管扩张剂给药途径的系统研究。目的:探讨定量(1.5 mg/Kg)罂粟碱不同给药途径对兔腹壁浅动脉皮瓣血管阻力的影响,寻找出一种最佳的给药途径,提高皮瓣存活率,并减少药物引起的不良反应和并发症,具有较大的实用价值。材料与方法:①选用雄性新西兰兔24只,实验方法符合动物伦理学要求。采用完全随机设计,按给药途径把24只兔分成4组(n=6),即皮瓣蒂部皮下注射组、皮瓣中央皮下注射组、臀部肌肉注射组及静脉推注组。②建立下腹部腹壁浅动脉皮瓣模型。术后1 h～7 d,按实验方案要求的部位注射罂粟碱,剂量为1.5 mg/Kg,1次/d。③术后1 h～7 d,利用彩色多普勒超声监测、比较分析近距离靶部位(皮瓣蒂部、皮瓣中央皮下)、远距离全身(传统臀部肌肉注射、静脉推注)注射罂粟碱前,注射罂粟碱后10 min,60 min时间点的血流阻力指数。④在统计方法上,使用spss11.5统计软件包处理数据,各处理组间术前皮瓣血流阻力指数的比较和各处理组间术后皮瓣血流阻力指数的比较用完全随机方差分析Duncan多重比较法;各组内术前及术后注药前皮瓣血流阻力指数用配对t检验;各组间皮瓣各时间点的血流阻力指数显著性检验均采用完全随机方差分析Duncan多重比较法。上述各统计学处理均规定P＜0.05为差异有显著性意义。结果:24只兔的实验数据全部进入结果分析。①术后各组皮瓣的血流阻力指数均高于术前(P＜0.05)。②术后注药后10min静脉注射组与皮瓣中央组的皮瓣血流阻力指数无显著性差异(P＞0.05),但均低于皮瓣蒂部注射组和臀甲⑸渥?有显著性差异(P＜0.05);手术后第1天、第2天、第4天注药后10min皮瓣蒂部注射组、静脉注射组和皮瓣中央皮下注射组之间皮瓣血流阻力指数比较无显著性差异(P＞0.05),但低于臀部肌肉注射组,差异具有显著性意义(P＜0.05);手术后第3天、第5天注药后10min皮瓣蒂部注射组、静脉注射组和臀部肌肉注射组之间皮瓣血流阻力指数比较无显著性差异(P＞0.05),但皮瓣中央皮下注射组皮瓣血流阻力指数最低,与其余三组差异具有显著性意义(P＜0.05);手术后第6天、第7天注药后10min皮瓣血流阻力指数无显著性差异(P＞0.05)。③手术后注药后1h各组之间的皮瓣血流阻力指数比较,无显著性差异(P＞0.05);手术后第1天、第2天、第3天注药后1h皮瓣中央皮下注射组的皮瓣血流阻力指数最低,与臀部肌肉注射组相比差异具有显著性意义(P＜0.05),与其他两组差异无显著性意义(P＞0.05);手术后第4天注药后1h皮瓣中央皮下注射组的皮瓣血流阻力指数最低,与其他3组差异具有显著性意义(P＜0.05);手术后第5天注药后1 h除臀部肌肉注射组略高于手术前(0.542±0.058)外,其他各组的皮瓣血流阻力指数均略低于手术前,3组之间差异无显著性意义(P＞0.05);手术后第6天、第7天注药后1 h各组之间皮瓣血流阻力指数比较,无显著性差异(P＞0.05)。结论:①移植皮瓣术后应用罂粟碱,经皮瓣蒂部皮下注射、皮瓣中央皮下注射、臀部肌肉注射及静脉推注四种给药途径,均能明显降低皮瓣的血流阻力指数。②移植皮瓣术后应用罂粟碱,经皮瓣中央皮下注射给药降低皮瓣的血流阻力指数效果最好,臀肌注射给药降低皮瓣的血流阻力指数效果最差。更多还原

【Abstract】 Background:With the development of microscopic surgery,transplantation of skin flaps has become the most effective method for repairing the traumatic tissue defection.There were visible muscle layer on the blood vessel,which has high sensitivity to all kinds of physical and chemical stimulation.So spasm occured to the anastomotic and the nearby section vessel very easily,which was the common complication during or after the microsurgical operation.The severe and lasting vasospasm resulted in transplanted tissue ischemia and hypoxia and even necrosis, thus induced the failure of operation.In clinical application,after operation of microscopic vascular of skin flaps,vasodilatator such as papaverine was frequently used to prevent and relieve vasospasm,increase cyclic blood flow of skin flaps and significantly reinforced skin flaps survivial capability.There were two major injection approaches:(1) using intramuscular injection in the buttocks many times per day for many days;(2) intravenous injection for 24 hours.Although clinical effects were good,the two methods still existed different degree of defect.If couldn’t control the speed of drug in intravenous injection,or injected too much,which would easily lead to severe bad reaction such as arrhythmia and blood pressure decrease,and aggravate ischemia and hypoxia in transplanted tissue;to intramuscular injection in muscle of buttocks,if dosage is too great,patients could not tolerant,but dosage is too low,the effects of spasmolysis were poor.Experiment results also showed that papaverine has been absorbed and distributed by 30～60 mg after intramuscular injection or intravenous injection,the concentration of drug acted on the remote end was very tiny, by calculating only several microgram could reach fingers.However,vasodilator drugs has not been conventional used in locally applied of flaps,and how to effects? At present,there was not system study about injection approaches of vasodilators by close distance of flaps.Objective:To investigate the influence of quantified papaverine(1.5 mg/kg) by different injection approaches on peripheral resistance of hypogastrium superficial epigastric artery skin flaps of rabbits,we explore the best administration approach to increase the survival ratio of skin flaps and reduce the adverse drug reactions and complications,which has considerable practical value.Material and methods:①Twenty-four male New Zealand rabbits were selected and randomized into 4 groups(n=6):skin flaps pedicle subcutaneous injection group,skin flaps center subcutaneous injection group,intramuscular injection group and intravenous injection group.The experimental procedure was accorded with animal ethical standards.②Bilateral hypogastric flap models were set up,and quantified papaverine(1.5 mg/kg) was administrated in each group by different approaches 1-7 hours postoperatively,once per day.③The resistance index of skin flaps were observed and comparative analysis by color Doppler ultrasound before operation,before injection,10 minutes and 1 hour after injection with one week after operation at close-distance targeted position(skin flap pedicle, skin flap center) and long-distance systemic(intramuscular injection,intravenous injection).④The results were analyzed by SPSS11.5 statistical package including paired T test and duncan’s test,A P value of＜0.05 was considered significant.Results:Twenty-four rabbits were included in final analysis.①The resistance index of flap blood flow in each group after operation was higher than before operation(P＜0.05).②The postoperative index of flap blood in skin flaps center group at 10 minutes after injection was no significant difference from intravenous injection group(P＞0.05).But they were lower than skin flaps pedicle subcutaneous injection group and intramuscular injection group,both of them have a statistical signification(P＜0.05).There was no statistical difference among these postoperative resistance index of flap blood flow of the skin flaps pedicle subcutaneous injection group and skin flaps center subcutaneous injection group and intravenous injection group at 10 minutes after injection on the first and second and fourth day(P＞0.05). But they were significantly lower than the intramuscular injection group(P＜0.05). There was no statistical difference among these postoperative resistance index of flap blood flow of the skin flap pedicle subcutaneous injection group and intramuscular injection group and intravenous injection group at 10 minutes after injection on the third and fifth day(P＞0.05),but the postoperative resistance index of flap blood flow of the skin flap center subcutaneous injection group was the lowest than others and it was a statistical signification(P＜0.05).There was no statistical difference among these postoperative resistance index of flap blood flow of the all group at 10 minutes after injection on the sixth and seventh day(P＞0.05).③There was no statistical difference among these postoperative resistance index of flap blood flow of the all groups at 1 hour after injection(P＞0.05),the postoperative resistance index of flap blood flow of the skin flap center subcutaneous injection group was the lowest at 1 hour after injection on the first and second and third day,there was a statistical signification compared with the intramuscular injection group(P＜0.05),but no statistical difference compared with other two groups(P＞0.05).The postoperative resistance index of flap blood flow of the skin flap center subcutaneous injection group was the lowest at 1 hour after injection on fourth day,there was statistical signification(P＜0.05).The postoperative resistance index of flap blood flow of the intramuscular injection group was slightly higher than preoperative at 1 hour after injection on fifth day(0.542±0.058),the others three resistance index were slightly lower preoperative,there was no statistical difference among three groups(P＞0.05). There was no statistical difference among these postoperative resistance index of flap blood flow of the all group at 1 hour after injection on sixth and seventh day(P＞0.05).Conclusion:①The papaverine could significantly decrease resistance index by skin flap pedicle subcutaneous injection and skin flap center intravenous injection and subcutaneous injection and intramuscular injection after operation.②After skin flap operating,papaverine injection in skin flap center achieves the best effect of decreasing resistance index,and intramuscular injection shows the worst effect of decreasing resistance.更多还原