Chronic glucagon-like peptide-1 infusion sustains left ventricular systolic function and prolongs survival in the spontaneously hypertensive, heart failure-prone rat.
Chronic glucagon-like peptide-1 infusion sustains left ventricular systolic function and prolongs survival in the spontaneously hypertensive, heart failure-prone rat.
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DOI：
10.1161/circheartfailure.108.766402
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发表时间：
2008-09
期刊：
影响因子：
--
通讯作者：
Shannon RP
中科院分区：
文献类型：
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作者：
Poornima I;Brown SB;Bhashyam S;Parikh P;Bolukoglu H;Shannon RP
GLP-1治疗导致缺血性和非缺血性心肌病中心肌功能的短期改善。目前尚不清楚GLP-1在较长时间内给药是否能改善生存率。自发性高血压心力衰竭易感大鼠（SHHF）在15个月内进展为晚期心力衰竭和死亡。我们试图确定连续输注GLP-1是否会降低该模型中的死亡率。在9月龄时，将50只SHHF大鼠随机接受GLP-1或盐水的3个月连续输注。在研究开始和治疗完成时测量代谢参数并进行心脏超声检查。在12个月时对存活大鼠实施安乐死。在离体等容心脏制备物中灌注心脏，并对心肌样品进行Tunel染色。基线代谢和心功能参数相当。GLP-1处理的SHHF在12月龄时具有更高的存活率（72% vs. 44%，p =0.008）。此外，GLP-1治疗导致血浆胰岛素升高、血浆甘油三酯降低和LV功能保留。GLP-1处理的大鼠通过Tunel染色显示肌细胞凋亡减少，以及半胱天冬酶-3活化减少。未观察到p-BAD表达增加。在离体心脏中，GLP-1组的LV收缩压和发展压力更大。在GLP-1处理的SHHF中，心肌葡萄糖摄取也增加。长期GLP-1治疗可延长肥胖、高血压SHHF患者的生存期。这与左心室功能和左心室质量指数的保留、心肌葡萄糖摄取的增加和心肌细胞凋亡的减少有关。
GLP-1 treatment leads to short term improvements in myocardial function in ischemic and non-ischemic cardiomyopathy. It is unknown whether GLP-1 improves survival when administered over a longer time period. Spontaneously hypertensive, heart failure prone rats (SHHF) progress to advanced heart failure and death over a 15 month period. We sought to determine whether a continuous infusion of GLP-1 would reduce mortality in this model. At 9 months of age, 50 SHHF rats were randomized to receive a 3-month continuous infusion of either GLP-1 or saline. Metabolic parameters were measured and cardiac ultrasounds performed at study initiation and completion of treatment. Surviving rats were euthanized at 12 months. Hearts were perfused in an isolated, isovolumic heart preparation and Tunel staining of myocardial samples was performed. Baseline metabolic and cardiac functional parameters were comparable. GLP-1 treated SHHF had greater survival (72% vs. 44%, p =0.008) at 12 months of age. In addition, GLP-1 treatment led to higher plasma insulin, lower plasma triglycerides, and preserved LV function. GLP-1 treated rats demonstrated decreased myocyte apoptosis by Tunel staining, as well as reduced caspase-3 activation. No increase in p-BAD expression was seen. In isolated hearts, the LV systolic pressure and developed pressure were greater in the GLP-1 group. Myocardial glucose uptake was also increased in GLP-1 treated SHHF. Chronic GLP-1 treatment prolongs survival in obese, hypertensive SHHF. This is associated with preserved LV function and LV mass index, increased myocardial glucose uptake and reduced myocyte apoptosis.