von Degenfeld Georges, Raake Philip, Kupatt Christian, Lebherz Corinna, Hinkel Rabea, Gildehaus Franz Josef, Münzing Wolfgang, Kranz Andrea, Waltenberger Johannes, Simoes Marcus, Schwaiger Markus, Thein Eckart, Boekstegers Peter
Internal Medicine I, Grosshadern, Grosshadern University Hospital, Munich, Germany.
J Am Coll Cardiol. 2003 Sep 17;42(6):1120-8. doi: 10.1016/s0735-1097(03)00915-x.
We sought to improve regional myocardial delivery and subsequent collateral perfusion induced by basic fibroblast growth factor-2 (FGF-2) using selective pressure-regulated retroinfusion of coronary veins for delivery. This hypothesis was tested in a newly developed pig model with percutaneous induction of chronic ischemia.
Selective pressure-regulated retroinfusion of coronary veins is a catheter-based procedure that has been shown to provide effective regional delivery of drugs and gene vectors into ischemic myocardium.
A high-grade stenosis with subsequent progression to total occlusion within 28 days was induced by implanting a reduction stent graft into the left anterior descending artery (LAD). After seven days, a 30-min retroinfusion (anterior cardiac vein) was performed with (n = 7) or without (n = 7) 150 microg FGF-2 and compared with a 30-min antegrade infusion of 150 microg FGF-2 into the LAD (n = 7). Sonomicrometry to assess regional myocardial function at rest and during pacing, and microspheres to assess regional myocardial blood flow, were performed 28 days after implantation of the reduction stent.
Retroinfusion of FGF-2 compared favorably with controls and with antegrade infusion of FGF-2 with regard to regional myocardial function at rest (18.5 +/- 4.1% vs. 5.7 +/- 2.9% vs. 7.9 +/- 1.8%, respectively, p < 0.05) and during pacing. Regional myocardial blood flow was also higher in the LAD territory after retroinfusion of FGF-2 (1.07 +/- 0.14 vs. 0.66 +/- 0.07 vs. 0.72 +/- 0.17 ml x min(-1) x g(-1), p < 0.05).
Selective pressure-regulated retroinfusion increased tissue binding of FGF-2 and enhanced functionally relevant collateral perfusion compared with antegrade intracoronary delivery in pigs with chronic myocardial ischemia.
我们试图通过使用选择性压力调节冠状静脉逆向输注法来改善碱性成纤维细胞生长因子-2（FGF-2）诱导的局部心肌递送及随后的侧支灌注。该假设在新建立的经皮诱导慢性缺血的猪模型中进行了验证。
选择性压力调节冠状静脉逆向输注是一种基于导管的操作，已被证明能有效地将药物和基因载体局部递送至缺血心肌。
通过向左前降支（LAD）植入缩窄支架移植物，诱导出严重狭窄并在28天内进展为完全闭塞。7天后，对7只猪进行30分钟的逆向输注（前心静脉），其中加入150微克FGF-2（n = 7），另外7只猪不加FGF-2作为对照，并与向LAD顺行输注150微克FGF-2的7只猪进行比较（n = 7）。在植入缩窄支架28天后，进行体腔测量以评估静息和起搏时的局部心肌功能，并用微球评估局部心肌血流。
在静息时（分别为18.5±4.1%对5.7±2.9%对7.9±1.8%，p < 0.05）和起搏时，FGF-2逆向输注在局部心肌功能方面优于对照组和顺行输注FGF-2。FGF-2逆向输注后，LAD区域的局部心肌血流也更高（1.07±0.14对0.66±0.07对0.72±0.17毫升·分钟-1·克-1，p < 0.05）。
在慢性心肌缺血的猪中，与冠状动脉顺行给药相比，选择性压力调节逆向输注增加了FGF-2的组织结合，并增强了功能相关的侧支灌注。
