The combined use of HGF gene therapy and ventricular assist device improves left ventricular function and enables bridge to recovery in goat model of severe heart failure

终末期心力衰竭患者需要在心室辅助装置（VAD）下数月甚至数年，直至接受心脏移植。在本研究中，我们对需要VAD支持的山羊热衰竭模型进行了肝细胞生长因子（HGF）基因治疗，并检查了“恢复桥”的可能性。6只成年山羊（56- 65 kg）接受了左冠状动脉前降支结扎，发生严重充血性心力衰竭，并接受了双心室VAD（BiVAD）植入术。HGF组直接心肌内注射HGF c-DNA质粒2.0mg，对照组注射空质粒，在BiVAD支持下，所有山羊均维持良好的体循环和左室去负荷，4周后尝试脱离VAD。肝细胞生长因子组在去除VAD后血流动力学良好，而对照组血流动力学明显恶化。与对照组相比，HGF组的%FS明显改善，左室扩张明显抑制（HGF vs.对照组，%FS;36±0.8vs24± 0.6%，LVDd;34± 2 vs 46 ± 2 mm，p<0.05）。组织学上，梗死区周围的血管密度显着增加，和纤维化的变化被抑制在HGF group.In结论，这些结果表明，基因治疗使用HGF可能会增加“桥恢复”的受损心脏需要VAD支持的机会。

Patients with end-stage heart failure require several months and even years under ventricular assist device (VAD) until receiving heart transplantation. Therefore, additional therapy such as regeneration therapy that promotes recovery of cardiac function is desired.In this study, we performed gene therapy with Hepatocyte Growth Factor (HGF) in the goat heat failure model requiring VAD support and examined the possibility of "bridge to recovery".Six adult goats (56-65kg) underwent ligation of the left anterior descending coronary artery, developed severe congestive heart failure and received the implantation of biventricular VAD (BiVAD). The HGF group was administered HGF c-DNA-plasmid of 2.0mg directly in myocardium, and the control group was administered empty plasmid.Under the BiVAD support, all goats maintained good systemic circulation and LV unloading for four weeks and after that periods we tried weaning from VAD. The HGF group showed good hemodynamics after the removal of VAD, while the control group showed the significant deterioration of hemodynamic condition. The %FS was significantly improved and LV dilatation was markedly suppressed in the HGF group than the control group (HGF vs. control, %FS;36±0.8vs24±0.6%, LVDd;34±2vs46±2mm, p<0.05). Histologically, vascular density around the infarcted area was markedly increased, and fibrous change was suppressed in the HGF group.In conclusion, these results suggest that gene therapy using HGF may increase the chance of "bridge to recovery" in the impaired heart requiring VAD support.