Strauss B H, Wilson R A, van Houten R, van Suylen R J, Murphy E S, Escaned J, Verdouw P D, Serruys P W, van der Giessen W J
Department of Cardiology, Erasmus University Rotterdam, The Netherlands.
Coron Artery Dis. 1994 Jul;5(7):633-41. doi: 10.1097/00019501-199407000-00012.
Balloon angioplasty damages endothelial cells and stimulates smooth muscle cell proliferation. The effects of local cytotoxic drug therapy on formation of neointima and late endothelial function are not known. This study was designed to determine whether direct infusion of mitomycin C via a microporous balloon catheter could significantly reduce formation of neointima after angioplasty. Furthermore, we investigated whether endothelial cell function is normal 7 weeks after the initial microporous angioplasty procedure.
In 34 New Zealand white rabbits, bilateral external iliac arteries underwent balloon angioplasty, followed by either high-dose (0.66 mg/kg) or low-dose (0.025 mg/kg) mitomycin C in one iliac artery and saline infusion in the contralateral artery, and a control group was given saline in both vessels. Formation of neointima was measured in the iliac arteries after 7 weeks by morphometry. Before sacrifice of 17 'angioplasty' rabbits and three undamaged rabbits, graded doses of acetylcholine and isosorbide dinitrate were infused in the distal aorta, and the iliac artery diameter was measured by computerized quantitative angiography.
No significant differences in the absolute area of the intima or the intima: media ratio were demonstrated between control arteries and arteries that were directly infused with either high-dose or low-dose mitomycin. However, within the high-dose group, the mitomycin-treated vessel had a significantly lesser extent of formation of intimal hyperplasia (0.17 +/- 0.03 versus 0.27 +/- 0.03 mm2, P < 0.03) and lower intima: media area ratio (0.60 +/- 0.31 versus 1.09 +/- 0.42, P < 0.03) than the contralateral saline-treated vessel. Significant increases in mean luminal iliac artery diameter [0.18 mm (10.5%) at 1 min and 0.23 mm (13%) at 3 min, P < 0.05)] from baseline values following acetylcholine were observed in previously damaged iliac arteries. This vasodilatory response was not different from that in undamaged arteries.
Local delivery of mitomycin C had no favorable effect on the inhibition of intimal hyperplasia compared with control saline-treated arteries. Normal endothelial function, determined on the basis of dilatory response to acetylcholine, can be demonstrated 7 weeks after balloon angioplasty injury.
球囊血管成形术会损伤内皮细胞并刺激平滑肌细胞增殖。局部细胞毒性药物治疗对新生内膜形成和晚期内皮功能的影响尚不清楚。本研究旨在确定通过微孔球囊导管直接注入丝裂霉素C是否能显著减少血管成形术后新生内膜的形成。此外，我们还研究了在初次微孔血管成形术7周后内皮细胞功能是否正常。
对34只新西兰白兔的双侧髂外动脉进行球囊血管成形术，然后在一侧髂动脉注入高剂量（0.66mg/kg）或低剂量（0.025mg/kg）的丝裂霉素C，对侧动脉注入生理盐水，对照组的两只血管均注入生理盐水。7周后通过形态计量学测量髂动脉新生内膜的形成情况。在处死17只“血管成形术”兔子和3只未受损兔子之前，向远端主动脉注入分级剂量的乙酰胆碱和硝酸异山梨酯，并通过计算机定量血管造影测量髂动脉直径。
对照组动脉与直接注入高剂量或低剂量丝裂霉素的动脉在内膜绝对面积或内膜：中膜比值方面无显著差异。然而，在高剂量组中，与对侧注入生理盐水的血管相比，经丝裂霉素处理的血管内膜增生形成的范围明显较小（0.17±0.03对0.27±0.03mm²，P<0.03），内膜：中膜面积比值较低（0.60±0.31对1.09±0.42，P<0.03）。在先前受损的髂动脉中，观察到乙酰胆碱作用后平均髂动脉管腔直径较基线值显著增加[1分钟时增加0.18mm（10.5%），3分钟时增加0.23mm（13%），P<0.05]。这种血管舒张反应与未受损动脉的反应无差异。
与对照组注入生理盐水的动脉相比，局部递送丝裂霉素C对抑制内膜增生没有有利影响。基于对乙酰胆碱的舒张反应确定的正常内皮功能在球囊血管成形术损伤7周后可以得到证实。
