在无法进行手术的心绞痛患者中，采用VEGF-A165质粒进行心肌基因治疗后，心肌组织多普勒速度得到改善。

Myocardial Doppler tissue velocity improves following myocardial gene therapy with VEGF-A165 plasmid in patients with inoperable angina pectoris.

作者信息

Sylvén C, Sarkar N, Rück A, Drvota V, Hassan S Y, Lind B, Nygren A, Källner Q, Blomberg P, van der Linden J, Lindblom D, Brodin L A, Islam K B

机构信息

Karolinska Institute, Department of Cardiology, Huddinge University Hospital, Novum, Stockholm, Sweden.

出版信息

Coron Artery Dis. 2001 May;12(3):239-43. doi: 10.1097/00019501-200105000-00010.

DOI:10.1097/00019501-200105000-00010

PMID:11352080

Abstract

BACKGROUND

Myocardial tissue velocity and perfusion were studied in patients with severe angina pectoris following gene therapy by intramyocardial injection of phVEGF-A165 via thoracotomy. Plasma concentrations of VEGF-A increased postoperatively. Two months after treatment anginal status and myocardial tissue velocity improved and perfusion showed a tendency to improve. Tissue velocity imaging appears to be a sensitive, objective method for detecting changes in myocardial function following gene therapy.

OBJECTIVE

To study effects on myocardial tissue velocity and perfusion in patients with angina pectoris following intramyocardial injection of phVEGF-A165 via thoracotomy.

DESIGN

Open label, phase I/II.

METHODS

Six patients with Canadian Cardiovascular Society (CCS) angina pectoris functional class III - IV and with major defects at adenosine stress single-photon emission computerized tomography (SPECT) were studied. In addition to SPECT, coronary angiography and dobutamine stress echocardiography with tissue Doppler velocity imaging were performed before and two months after gene transfer.

RESULTS

Plasma concentrations of VEGF-A increased 2 to 3 times (P < 0.04) over baseline from 2 to 14 days after injection with normalization after 4 weeks. The CCS class improved about 40%, from 3.3 +/- 0.2 to 2.0 +/- 0.3 (P < 0.02) and nitroglycerine consumption decreased 30 - 40%, from 44 +/- 17 to 15 +/- 5 tablets per week (P < 0.05). The maximal systolic myocardial tissue velocity increased in all patients about 25% (P < 0.02) but did not reach the reference range. Myocardial perfusion at SPECT improved in four of the six patients.

CONCLUSIONS

Anginal status, myocardial tissue velocity and perfusion can be improved by phVEGF-A165 intramyocardial injection. Tissue velocity imaging appears to be a sensitive, objective method for detecting changes in myocardial function following gene therapy.

摘要

背景

通过开胸手术心肌内注射phVEGF - A165对严重心绞痛患者进行基因治疗后，对其心肌组织速度和灌注情况进行了研究。术后血浆VEGF - A浓度升高。治疗两个月后，心绞痛状态和心肌组织速度改善，灌注有改善趋势。组织速度成像似乎是检测基因治疗后心肌功能变化的一种敏感、客观的方法。

目的

研究开胸手术心肌内注射phVEGF - A165对心绞痛患者心肌组织速度和灌注的影响。

设计

开放标签，I/II期。

方法

对6例加拿大心血管学会（CCS）心绞痛功能分级为III - IV级且腺苷负荷单光子发射计算机断层扫描（SPECT）有主要缺损的患者进行了研究。除SPECT外，在基因转移前和转移后两个月进行了冠状动脉造影和多巴酚丁胺负荷超声心动图检查及组织多普勒速度成像。

结果

注射后2至14天，血浆VEGF - A浓度比基线水平升高2至3倍（P < 0.04），4周后恢复正常。CCS分级改善约40%，从3.3±0.2降至2.0±0.3（P < 0.02），硝酸甘油消耗量减少30 - 40%，从每周44±17片降至15±5片（P < 0.05）。所有患者的最大收缩期心肌组织速度增加约25%（P < 0.02），但未达到参考范围。6例患者中有4例SPECT心肌灌注改善。