Glucagon-like peptide-1 (7-36) but not (9-36) augments cardiac output during myocardial ischemia via a Frank-Starling mechanism.
Glucagon-like peptide-1 (7-36) but not (9-36) augments cardiac output during myocardial ischemia via a Frank-Starling mechanism.
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DOI：
10.1007/s00395-014-0426-9
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发表时间：
2014
影响因子：
9.5
通讯作者：
Mather KJ
中科院分区：
文献类型：
--
作者：
Goodwill AG;Tune JD;Noblet JN;Conteh AM;Sassoon D;Casalini ED;Mather KJ
本研究观察了GLP-1(7-36)或(9-36)在正常灌流和急性局部心肌缺血期间对在体心肌耗氧量、功能和全身血流动力学的影响。以1.5、3.0、10.0pmoL/kg/min的速度依次全身注射生理盐水或GLP-1(7-36或9-36)30min，然后以10.0pmol/kg/min的速度结扎左旋支动脉。系统性GLP-1(9-36)对局部心肌缺血前后冠脉流量、血压、心率及心功能指标均无影响。系统性GLP-1(7-36)在缺血前对心脏代谢或血流动力学无影响。在缺血期间，GLP-1(7-36)使心输出量增加约2 L/分钟，与空白对照组相比(p=0.003)。使用非去极化神经节阻滞剂六甲溴铵治疗后，这种反应不会减弱。结果显示，GLP-1(7-36)在局部缺血时舒张末容量(74±1至92±5毫升；p=0.03)和容量轴截距(8±2至26±8；p=0.05)显著增加，收缩末压-容量关系斜率与负荷无关。与车辆相比，GLP-1(9-36)在这些参数中没有任何变化。这些发现表明，在局部心肌缺血期间，使用GLP-1(7-36)而不是GLP-1(9-36)的短期全身治疗可显著增加心输出量，这是通过增加心室前负荷而不改变心脏变力来实现的。
This study examined the cardiovascular effects of GLP-1 (7–36) or (9–36) on myocardial oxygen consumption, function and systemic hemodynamics in vivo during normal perfusion and during acute, regional myocardial ischemia. Lean Ossabaw swine received systemic infusions of saline vehicle or GLP-1 (7–36 or 9–36) at 1.5, 3.0, and 10.0 pmol/kg/min in sequence for 30 min at each dose, followed by ligation of the left circumflex artery during continued infusion at 10.0 pmol/kg/min. Systemic GLP-1 (9–36) had no effect on coronary flow, blood pressure, heart rate or indices of cardiac function before or during regional myocardial ischemia. Systemic GLP-1 (7–36) exerted no cardiometabolic or hemodynamic effects prior to ischemia. During ischemia, GLP-1 (7–36) increased cardiac output by approximately 2 L/min relative to vehicle-controls (p=0.003). This response was not diminished by treatment with the non-depolarizing ganglionic blocker hexamethonium. Left ventricular pressure-volume loops measured during steady state conditions with graded occlusion of the inferior vena cava to assess load-independent contractility revealed that GLP-1 (7–36) produced marked increases in end diastolic volume (74 ± 1 to 92 ± 5 mL; p=0.03) and volume axis intercept (8 ± 2 to 26 ± 8; p=0.05), without any change in the slope of the end systolic pressure volume relationship vs. vehicle during regional ischemia. GLP-1 (9–36) produced no changes in any of these parameters compared to vehicle. These findings indicate that short-term systemic treatment with GLP-1 (7–36) but not GLP-1 (9–36) significantly augments cardiac output during regional myocardial ischemia, via increases in ventricular preload without changes in cardiac inotropy.
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影响因子：
9.5
作者：
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作者：
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通讯作者：
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作者：
Nguyen, T. Dung;Shingu, Yasushige;Doenst, Torsten
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