Platelet-derived growth factor improves cardiac function in a rodent myocardial infarction model.
Platelet-derived growth factor improves cardiac function in a rodent myocardial infarction model.
复制标题
血小板衍生生长因子可改善啮齿动物心肌梗死模型中的心脏功能。
DOI：
10.1097/00019501-200402000-00009
复制
发表时间：
2004
影响因子：
1.8
通讯作者：
Edelberg,JayM
中科院分区：
文献类型：
--
作者：
Zheng,Jingang;Shin,JinH;Xaymardan,Munira;Chin,Andrew;Duignan,Inga;Hong,MunK;Edelberg,JayM
心肌梗死的心脏保护治疗需要临床前证实急性冠状动脉闭塞后心血管功能的改善。我们以前的研究表明，用血小板衍生生长因子（PDGF）预处理啮齿动物心脏可促进血管生成，并降低组织学测量的心肌损伤程度。本研究的目的是确定这些组织学结果的相关性与非侵入性措施的改善在cardiac function.MethodsRats心肌内注射PDGF（100 ng）或磷酸盐缓冲液（PBS）（每组n= 6）急性给药前24 h，14天后通过Masson三色染色评估左前降支永久结扎和心肌损伤程度。为了评估冠状动脉闭塞后PDGF预处理的生理效应，通过心电图、运动试验和超声心动图非侵入性地评估心脏功能，并与直接组织学测量结果相关。（基线以上0.12±0.02 mV; P< 0.05）。冠脉闭塞后14天运动试验显示，PDGF预处理组大鼠最大运动速度（28.54±3.98 m/min）明显快于对照组（24.98±3.13 m/min; P< 0.05）。超声心动图显示，PDGF预处理组大鼠左室收缩率（18.47±12.21%）显著高于对照组（4.91±7.21%）（P< 0.05）。基于PDGF的心脏保护作用的策略可能为心肌梗死的治疗提供显著的进展。
ObjectivesThe translation of cardioprotective therapies for myocardial infarction requires a preclinical demonstration of improved cardiovascular function following acute coronary occlusion. We previously showed that pretreatment of rodent hearts with platelet-derived growth factor (PDGF) promotes angiogenesis and decreases the extent of myocardial injury measured by histology. The present study aimed to determine the correlation of these histological findings with noninvasive measures of improvement in cardiac function.MethodsRats were treated with intramyocardial injections of PDGF (100 ng) or phosphate buffer solution (PBS)(n= 6 per group) 24 h prior to acute, permanent ligation of the left anterior descending artery and the extent of myocardial injury was assessed by Masson's trichrome staining 14 days later. To assess the physiological effects of PDGF pretreatment after coronary occlusion, cardiac function was assessed noninvasively by electrocardiography, exercise testing and echocardiography and correlated with direct histological measures.ResultsPhysiological studies demonstrated that PDGF resulted in lower ST-segment elevation at the time of coronary occlusion (0.12±0.02 mV above baseline) than in PBS control rats (0.35±0.05 mV; P< 0.05). Exercise testing 14 days after coronary occlusion revealed that PDGF pretreatment resulted in faster maximal exercise speeds (28.54±3.98 m/min) than in control rats (24.98±3.13 m/min; P< 0.05). Echocardiography also revealed that the left ventricular factional shortening in the PDGF-pretreated rats was significantly greater (18.47±12.21%) than in control animals (4.91±7.21%; P< 0.05).ConclusionsThese studies demonstrate that PDGF pretreatment improves cardiac function following acute coronary occlusion. Strategies based on the cardioprotective actions of PDGF may provide a significant advance in the treatment of myocardial infarction.