Delivery strategies to achieve therapeutic myocardial angiogenesis
Delivery strategies to achieve therapeutic myocardial angiogenesis
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DOI：
10.1161/01.cir.101.4.454
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发表时间：
2000-02-01
期刊：
影响因子：
37.8
通讯作者：
Epstein, SE
中科院分区：
文献类型：
--
作者：
Kornowski, R;Fuchs, S;Epstein, SE
利用重组基因或生长因子增强心肌侧支血管功能可能是治疗心血管疾病的一种新途径。概念验证已经在心肌缺血的动物模型中得到证实，临床试验正在进行中。目前，还不清楚哪种给药策略是在缺血心肌中诱导临床上重要的治疗性血管生成反应的最安全和最有效的给药策略，大多数血管生成因子的经导管给药策略都使用冠脉内途径，这可能由于基因或蛋白质的不精确定位和全身给药到非心脏组织而具有局限性。在实验模型中直接心肌内注射血管生成因子对侧支循环功能的影响已有报道，在患者的心内直视手术中直接心肌内注射血管生成多肽或质粒载体后，正在研究血管生成。以导管为基础的经心内膜内注射血管生成因子可以提供相同的益处，而不需要手术。由于心包的储藏功能，心包内输送血管生成因子可能提供一个理论上的优势，即冠状动脉或心肌组织长期暴露于给药药物中。本文就治疗性心肌血管生成治疗的不同给药方式进行综述。
The use of recombinant genes or growth factors to enhance myocardial collateral blood vessel function may represent a new approach to the treatment of cardiovascular disease. Proof of concept has been demonstrated in animal models of myocardial ischemia, and clinical trials are underway. Currently, it is unknown which is the safest and most effective delivery strategy to induce clinically important therapeutic angiogenic responses in ischemic myocardium, Most strategies fur transcatheter delivery of angiogenic factors have used an intracoronary route, which may have limitations because of imprecise localization of genes or proteins and systemic delivery to noncardiac tissue. The effect of direct intraoperative intramyocardial injection of angiogenic factors on collateral function has been reported in experimental models, and angiogenesis is being studied after direct intramyocardial injection of angiogenic peptides or plasmid vectors during open heart surgery in patients. Catheter-based transendocardial injection of angiogenic factors may provide equivalent benefit without the need for surgery. Intrapericardial delivery of angiogenic factors may offer a theoretical advantage of prolonged exposure of either coronary or myocardial tissue to the administered drug as result of a reservoir function of the pericardium. In this article, we review the different modes of administration for therapeutic myocardial angiogenesis therapy.