Adenosine diphosphate reduces infarct size and improves porcine heart function after myocardial infarct.
Adenosine diphosphate reduces infarct size and improves porcine heart function after myocardial infarct.
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DOI：
10.1002/phy2.3
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发表时间：
2013-06
影响因子：
2.5
通讯作者：
Rosenmeier, Jaya B
中科院分区：
文献类型：
--
作者：
Bune, Laurids T;Larsen, Jens R;Thaning, Pia;Bune, Nethe E T;Rasmussen, Peter;Rosenmeier, Jaya B
急性心肌梗塞仍然是发病率和死亡率的主要原因。及时再灌注可以显著改善结果，因此在再灌注期间给予心脏保护物质是非常有吸引力的。二磷酸腺苷（ADP）和尿苷-5-三磷酸（UTP）在心肌缺血时均释放，影响血流动力学。两者都介导组织纤溶酶原激活物（t-PA）的释放，这可以减少梗死面积（IS）。本研究的目的是调查是否外源性ADP和UTP管理在再灌注过程中可以减少心肌IS，这是否与t-PA释放或改善血流动力学反应。在22只猪的左前冠状动脉闭塞前，期间和45分钟后，测量血流动力学变量和t-PA。在再灌注期间，将猪随机分配至240分钟的ADP、UTP或对照（无干预）的冠状动脉内输注。测量缺血面积与风险面积[IS/AAR]的比较。[IS/AAR]为52 ± 11%。ADP使[IS/AAR]降低19%（P < 0.05），UTP使[IS/AAR]升高15%（P < 0.05）。ADP组心输出量（CO）从3.4 L/min增加到3.5 L/min（P < 0.05），平均动脉压（MAP）从87 mmHg下降到73 mmHg（P < 0.05）。ADP组和UTP组t-PA浓度分别从2.0 ng/mL增加到2.5和2.4 ng/mL（P < 0.05），而对照组无明显变化。总之，在再灌注期间冠状动脉内输注ADP可使IS降低约20%，与t-PA的全身释放无关。ADP诱导的前负荷和后负荷的减少可以解释有益的心肌效应。
Acute myocardial infarction continues to be a major cause of morbidity and mortality. Timely reperfusion can substantially improve outcomes and the administration of cardioprotective substances during reperfusion is therefore highly attractive. Adenosine diphosphate (ADP) and uridine-5-triphoshate (UTP) are both released during myocardial ischemia, influencing hemodynamics. Both mediate the release of tissue plasminogen activator (t-PA), which can reduce infarct size (IS). The objective of this study was to investigate whether exogenous ADP and UTP administration during reperfusion could reduce myocardial IS and whether this correlated to t-PA release or improvements in hemodynamic responses. Hemodynamic variables and t-PA were measured in 22 pigs before, during, and after 45 min of left anterior coronary artery occlusion. During reperfusion, the pigs were randomized to 240 min of intracoronary infusion of ADP, UTP, or control (no intervention). Ischemic area compared to the area at risk [IS/AAR] was measured. [IS/AAR] was 52 ± 11% in the control animals. ADP decreased [IS/AAR] by 19% (P < 0.05), while UTP increased [IS/AAR] by 15% (P < 0.05). Cardiac output (CO) increased from 3.4 to 3.5 L/min (P < 0.05) and mean arterial pressure (MAP) decreased from 87 to 73 mmHg in the ADP group (P < 0.05). t-PA concentration increased in the ADP and UTP group from 2.0 ng/mL to 2.5 and 2.4 ng/mL, respectively (P < 0.05) but remained unchanged in the control group. In conclusion, intracoronary ADP infusion during reperfusion reduces IS by ∼20% independently from systemic release of t-PA. ADP-induced reduction in both preload and afterload could account for the beneficial myocardial effect.