冠状静脉逆行灌注碱性成纤维细胞生长因子的体内浓度梯度

In vivo concentration gradient of basic fibroblast growth factor after coronary venous retrograde perfusion

背景:体外研究发现,碱性成纤维细胞生长因子浓度梯度能够促进干细胞的迁移和增殖。然而,采用冠状静脉逆行灌注途径能否建立在体碱性成纤维细胞生长因子浓度梯度尚不明确。目的:评价冠状静脉逆行灌注实验方法的安全性,建立并检测冠状静脉与局部缺血心肌间的碱性成纤维细胞生长因子浓度梯度,探讨逆行灌注后碱性成纤维细胞生长因子浓度梯度存在的时间窗。方法:开胸结扎法建立犬急性心肌梗死模型,1周后经冠状静脉逆行灌注碱性成纤维细胞生长因子。灌注结束后球囊充盈时间分别为0,5,10,15min。解除球囊充盈后即刻处死动物,ELISA法测量血浆和梗死区心肌、梗死边缘区心肌组织匀浆中碱性成纤维细胞生长因子的浓度,在体评价在不同时间点冠状静脉血液与梗死区心肌以及梗死边缘区心肌之间的碱性成纤维细胞生长因子浓度梯度。结果与结论:逆行灌注成功率为100%,无死亡、心脏压塞和恶性心律失常等并发症发生。灌注后5min和10min,冠状静脉血液与梗死区心肌之间碱性成纤维细胞生长因子浓度的差异有显著性意义,梗死区心肌浓度明显高于其他2种组织。球囊充盈15min后2组之间浓度差异无显著性意义。结果表明,经冠状静脉逆行灌注碱性成纤维细胞生长因子后,球囊充盈的时间为5-10min能在冠状静脉血液与梗死心肌之间建立稳定的碱性成纤维细胞生长因子浓度梯度,而且在梗死心肌区域浓度最高。此时间窗内灌注干细胞有望增强其移行活力。

BACKGROUND： In vitro studies have demonstrated that the concentration gradient of basic fibroblast growth factor can promote the migration and proliferation of stem cells. However, it is unclear whether in vivo basic fibroblast growth factor concentration gradient can be established by coronary venous retrograde perfusion. OBJECTIVE： To evaluate the safety of coronary venous retrograde perfusion and establish the concentration gradient of basic fibroblast growth factor between coronary venous blood and target myocardium, and to investigate the time window of basic fibroblast growth factor concentration gradient after coronary venous retrograde perfusion. METHODS： The acute myocardial infarction models were established with ligating method, and 1 week later, coronary venous retrograde perfusion of basic fibroblast growth factor was performed. After perfusion, the time of balloon dilation was 0, 5, 10 and 15 minutes. The animals were sacrificed immediately after balloon inflation lifting and then the enzyme-linked immunosorbent assay was used to measure the concentration of basic fibroblast growth factor in the plasma, farcted myocardium and homogenates of myocardium in the infarct border zone. The basic fibroblast growth factor concentration gradient between the coronary venous blood and infarcted myocardium and myocardium in the infarct border zone was in vivo evaluated. RESULTS AND CONCLUSION： The success rate of coronary venous retrograde perfusion was 100%. No death, cardiac tamponade, or ventricular arrthythmia occurred. There was no significant difference in concentration of basic fibroblast growth factor between coronary venous blood and infarcted myocardium at 5 and 10 minutes after perfusion, while the concentration of basic fibroblast growth factor in the infarcted myocardium was higher than that in the coronary venous blood and myocardium in the infarct border zone. There was no significant difference in the concentration between two groups after balloon dilation for 15 minutes. The results indicate that after coronary venous retrograde perfusion of basic fibroblast growth factor, the time of balloon dilation was 5-10 minutes which can establish stable basic fibroblast growth factor concentration gradient between the coronary venous blood and infarcted myocardium, and the concentration is highest in the infarcted myocardium. The stem cell infusion in this time window can enhance its transitional vitality.