EFFECTS OF CHRONIC SYSTEMIC ADMINISTRATION OF BASIC FIBROBLAST GROWTH-FACTOR ON COLLATERAL DEVELOPMENT IN THE CANINE HEART
EFFECTS OF CHRONIC SYSTEMIC ADMINISTRATION OF BASIC FIBROBLAST GROWTH-FACTOR ON COLLATERAL DEVELOPMENT IN THE CANINE HEART
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DOI：
10.1161/01.cir.91.1.145
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发表时间：
1995-01-01
期刊：
影响因子：
37.8
通讯作者：
UNGER, EF
中科院分区：
文献类型：
--
作者：
LAZAROUS, DF;SCHEINOWITZ, M;UNGER, EF
最近我们报道了冠状动脉内注射碱性成纤维细胞生长因子（bFGF），一种专利的血管生成肽，增加了进行性左回旋支冠状动脉（LCx）闭塞犬的侧支血流量。本研究的目的是检查全身给药的bFGF对侧支血流量的影响，并评估其药代动力学和潜在的副作用。方法和结果47只狗进行了渐进ameroid诱导闭塞的LCx，干预已知诱导侧支血管的发展。在研究的第一阶段，犬随机接受bFGF 1.74 mg/d（n = 10）或生理盐水（n = 9）作为左心房注射4周。在最大冠状动脉舒张期间，在清醒状态下用放射性标记微球连续评估相对侧支血流量。bFGF治疗的开始与侧支发育的显著加速在时间上相关;然而，对照犬的侧支血流在研究结束时有所改善，在38天终点接近bFGF治疗犬。研究的第二阶段是一项持续时间较长的三臂研究，以确定bFGF是否引起侧支功能的持续增加。犬随机接受bFGF 1.74 mg/d治疗9周（n = 7），bFGF 1.74 mg/d治疗5周，随后安慰剂治疗4周（n = 11），或安慰剂治疗9周（n = 10）。在冠状动脉最大血管扩张过程中，用微球连续评估相对和绝对侧支血流量。在ameroid放置后第10天和第17天之间，bFGF治疗的狗表现出侧支血流的显著改善，使得在5周交叉点处最大侧支传导超过对照组24%。最终侧支传导性在接受bFGF 5周和9周的狗中相似，尽管前一组中的治疗被撤销。bFGF给药与最终侧支传导增加21%以及侧支区血管密度增加49%相关。长期的bFGF管理也与动脉压，中度血小板减少症，中度，可逆性anemia.Conclusions全身施用bFGF增强侧支传导在狗进行性单血管冠状动脉闭塞的降低。bFGF的有益作用主要发生在治疗的第7天和第14天之间，并且在停止治疗后没有注意到侧支发展的消退。目前的调查提供了动力的概念，侧支的发展，可以提高药理学，特别是bFGF的可能性，这种干预可能最终应用于临床。
Background Recently we reported that intracoronary administration of basic fibroblast growth factor (bFGF), a patent angiogenic peptide, increases collateral blood flow in dogs subjected to progressive left circumflex coronary artery (LCx) occlusion. The aim of the present study was to examine the effect of systemically administered bFGF on collateral blood flow and to assess its pharmacokinetics and potential side effects.Methods and Results Forty-seven dogs were subjected to progressive ameroid-induced occlusion of the LCx, an intervention known to induce the development of collateral vessels. In phase I of the investigation, dogs were randomized to receive bFGF 1.74 mg/d (n=10) or saline (n=9) as a left atrial injection for 4 weeks. Relative collateral blood flow was assessed serially with radiolabeled microspheres in the conscious state during maximal coronary vasodilatation. Initiation of bFGF treatment was temporally associated with a marked acceleration of collateral development; however, collateral flow in control dogs improved toward the end of the study, approaching that of bFGF-treated dogs at the 38-day end point. Phase II of the investigation was a three-armed study of extended duration to determine whether bFGF caused a sustained increase in collateral function. Dogs were randomized to receive bFGF 1.74 mg/d for 9 weeks (n=7), bFGF 1.74 mg/d for 5 weeks followed by placebo for 4 weeks (n-11), or placebo for 9 weeks (n=10). Relative and absolute collateral blood flow were assessed serially with microspheres during maximal coronary vasodilatation. Between the 10th and 17th days after ameroid placement, bFGF-treated dogs exhibited marked improvement in collateral flow such that maximal collateral conductance exceeded that of controls by 24% at the 5-week crossover point. Final collateral conductance was similar in dogs receiving bFGF for 5 and 9 weeks despite withdrawal of treatment in the former group. bFGF administration was associated with a 21% increase in final collateral conductance as well as a 49% increase in collateral zone vascular density. Prolonged bFGF administration was also associated with a decrease in arterial pressure, moderate thrombocytopenia, and moderate, reversible anemia.Conclusions Systemic administration of bFGF enhanced collateral conductance in dogs with progressive single-vessel coronary occlusion. The beneficial effect of bFGF occurred primarily between the 7th and 14th days of therapy, and regression of collateral development was not noted after withdrawal of treatment. The present investigation provides impetus to the concept that collateral development can be enhanced pharmacologically-specifically by bFGF-raising the possibility that such an intervention might eventually be applied clinically.