经皮冠脉内腺病毒载体介导的血管内皮生长因子基因转移治疗严重冠心病

Percutaneous Gene Transfer of Intracoronary Adenovirus-mediated Vascular Endothelial Growth Factor 165 for Patients with Severe Coronary Artery Disease

目的 :观察经皮冠脉内腺病毒载体介导的血管内皮生长因子 (VEGF)基因转移治疗严重冠心病的疗效。方法 :2例病人均为严重弥漫性三支病变 ,临床上心绞痛为Ⅳ级 ,药物治疗效果不好 ,采用经皮冠脉内途径导入表达人VEGF16 5的腺病毒载体 (AdCMV .VEGF16 5 )。结果 :手术操作过程中 ,患者耐受良好 ,无不良反应发生。两例均在术后 1h出现一过性发热 ,持续 3h ,经处理后体温恢复正常。未发生心肌梗塞 ,心律失常 ,血流动学不稳定或心功能改变 ,随访 6周未出现与腺病毒载体有关的心脏及全身不良反应。 2例病人心绞痛症状均显著改善 (由术前每天需 18～ 2 0片消心痛至术后 3～ 6片 /d ,心绞痛分级由术前Ⅳ级提高至术后Ⅱ级 ) ,术后 45d时冠脉造影示冠脉闭塞区域心肌侧支循环增加。结论 :通过这 2例初步经验 ,提示经皮冠脉内腺病毒载体介导的VEGF16 5基因转移治疗严重冠心病可促进侧支循环形成以及临床心绞痛症状改善。

s: Objective To observe the effects of percutaneous intracoronary gene transfer of adenovirus-mediated vascular endothelial growth factor 165 in the treatment of patients with severe ischemic heart disease. Methods A replication-defective adenovirus vector expressing human vascular endothelial growth factor 165 cDNA(AdCMV.VEGF165) was percutaneously introduced into the coronary arteries of two patients with severe diffuse triple vessel disease, class IV angina, and bad response to antiangina medication. Results The two patients tolerated the procedures very well.A transient fever occured one hour after the procedure in both patients and the temperature returned to normal 3 hours later. No myocardial infarction,arrhythmia,hemodynamic instability,or change in ventricular function occurred,with no evidence of systemic or cardiac-related adverse events related to vector administration during the six weeks' follow-up. Both patients had significant reduction in angina (Isordil was reduced from 18-20 tablets/day before to 3-6 tablets/day after gene therapy,angina grade from Ⅳ to Ⅱ after therapy). Coronary angiographic evidence of improved collateral filling of at least one occluded coronary vessel was observed in both patients evaluated at 45 days after the operation. Conclusions This preliminary application of adenovius-mediated gene transfer to the treatment of myocardial ischemia suggests that percutaneous intracoronary infusion of adenevirus vector expressing VEGF165 may result in significant symptomatic improvement in patients with sever diffuse coronary artery disease.