Effects of Locally Applied Transdermal Nitroglycerin for the Treatment of Chronic Limb Ischemia

我们评估了局部应用经皮硝酸甘油（NTG）治疗外周血管疾病引起的慢性肢体缺血的效果，采用1)15例经皮PO2/PCO2张力（tcPO2/tcPCO2）测量，2)25例近红外光谱（NIRS）跑步机步行试验，3)9例皮肤血流和温度用激光多普勒测速仪测量，4)NTG血药浓度测量。同时进行tcPO2/PCO2和皮肤血流量测量。在缺血腿上涂敷5毫克的NTG贴片或12毫克的NTG软膏。局部应用NTG贴片，tcppo2从24.3【负加】19.6 mmHG显著升高至41.1【负加】22.0 mmHG (p<0.0001)， tcPCO2从50.1【负加】8.54 mmHG显著降低至44.5【负加】5.53 mmHG （p<0.001）。近红外光谱法测定的氧化血红蛋白恢复时间，在被测腿上应用NTG贴片（3.65【负加】2.06分钟，p<0.05）和对侧腿上应用NTG贴片（3.84【负加】2.20分钟，p<0.05）比未应用NTG贴片（4.26【负加】2.60分钟）显著缩短。应用NTG软膏后，皮肤血流量由101±66 BPU显著增加至196±116 BPU (p<0.01)，皮肤温度由30.5【负正】1.0℃显著升高至34.2【负正】1.2℃（p<0.001）。应用NTG软膏对未治疗的对侧腿部皮肤血流量无显著变化，但温度由32.0【负正】1.0℃显著升高至34.2【负正】1.3℃（p<0.05）。贴药30 min和120 min后，腿部股静脉NTG血药浓度分别为1.69【负正】1.67 ng/ml和9.99【负正】7.16 ng/mg，而肘静脉NTG血药浓度未检出。涂药120 min后，腿部股静脉NTG血药浓度为23.55【±±】27.46 ng/ml，显著高于肘静脉（0.40【±±】0.22 ng/ml），差异有统计学意义（p<0.05）。我们推测，NTG产生的一氧化氮在缺血的腿内高浓度存在，促进循环并提供有益的作用。综上所述，局部经皮给药NTG是治疗外周血管疾病的有效方法，且局部给药效果优于其他部位给药。少

We evaluated the effects of locally applied transdermal nitroglycerin (NTG) for the treatment of chronic limb ischemia due to peripheral vascular disease, using 1) transcutaneous PO2/PCO2 tension (tcPO2/tcPCO2) measurement in 15 patients, 2) treadmill walking test with near-infrared spectroscopy (NIRS) in 25 patients, 3) cutaneous blood flow and temperature measurement using laser Doppler velocimeter in 9 patients, and 4) measurement of blood concentration of NTG, simultaneously with tcPO2/PCO2 and cutaneous blood flow measurements. Five milligram NTG patches or 12 mg NTG ointments were applied to the ischemic legs.TcPO2 significantly increased from 24.3【minus-plus】19.6 mmHG to 41.1【minus-plus】22.0 mmHg (p<0.0001) and tcPCO2 significantly decreased from 50.1【minus-plus】8.54 mmHg to 44.5【minus-plus】5.53 mmHg (p<0.001) by local application of NTG patches. Recovery-time of oxyHb measured by NIRS significantly reduced, when NTG patches were applied to measured legs (3.65【minus-plus】2.06 mi … More nutes, p<0.05) and contralateral legs (3.84【minus-plus】2.20 min., p<0.05), compared with when which were not (4.26【minus-plus】2.60 min.). The cutaneous blood flow of the NTG applied legs significantly increased from 101±66 BPU to 196±116 BPU (p<0.01) and the cutaneous temperature significantly elevated from 30.5【minus-plus】1.0℃ to 34.2【minus-plus】1.2℃ (p<0.001) by application of NTG ointments. The cutaneous blood flow of the contralateral legs with no treatment did not significantly changed by application of NTG ointments, while the temperature significantly elevated from 32.0【minus-plus】1.0℃ to 34.2【minus-plus】1.3℃ (p<0.05). The NTG blood concentration of the femoral vein of the patches applied legs was 1.69【minus-plus】1.67 ng/ml and 9.99【minus-plus】7.16 ng/mg, respectively 30 min. and 120 min. after the application, whereas that of the cubital vein was not detectable. The NTG blood concentration of the femoral vein of the ointments applied legs was 23.55【minus-plus】27.46 ng/ml 120 min. after the application, significantly higher than that of the cubital vein (0.40【minus-plus】0.22 ng/ml), (p<0.05).We speculate that nitric oxide produced from NTG, which exists in high concentration within ischemic legs, enhances circulation and provided beneficial effects. In conclusion, the local transdermal administration of NTG to ischemic limb is a useful therapeutic method for the treatment of peripheral vascular disease, and the administration at the site of ischemia could provides larger effects than that at other sites. Less