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

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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