Transmural distribution of metabolic abnormalities and glycolytic activity during dobutamine-induced demand ischemia
Transmural distribution of metabolic abnormalities and glycolytic activity during dobutamine-induced demand ischemia
复制标题
DOI：
10.1152/ajpheart.01383.2007
复制
发表时间：
2008-06-01
影响因子：
4.8
通讯作者：
Zhang, Jianyi
中科院分区：
文献类型：
--
作者：
Jameel, Mohammad N.;Wang, Xiaohong;Zhang, Jianyi
左心室壁的异质性特征在于较高的耗氧率、收缩期增厚分数、心肌灌注和心内膜下层（ENDO）较低的能量状态。在多巴酚丁胺刺激引起的需求缺血期间，能量需求的跨壁分布和缺血的代谢标志物尚不清楚。本研究在基础条件下、多巴酚丁胺输注期间（DOB：20μg.kg(-1).min(-1) iv）和冠状动脉狭窄+DOB+2-脱氧葡萄糖（2-DG）输注期间测定血流动力学、透壁高能磷酸盐（HEP）、2-脱氧葡萄糖-6-磷酸（2-DGP）水平和心肌血流量（MBF）。 DOB 显着增加心率压力乘积 (RPP) 和 MBF，而不影响心内膜下与心外膜下血流比 (ENDO/EPI) 或 HEP 水平。冠状动脉狭窄+DOB+2-DG输注期间，RPP、缺血区（IZ）MBF和ENDO/EPI显着下降。磷酸肌酸与 ATP 的 IZ 比率显着下降 [EPI、心肌中层 (MID) 和 ENDO 分别为 2.30 +/- 0.14、2.06 +/- 0.13 和 2.04 +/- 0.11 至 1.77 +/- 0.12、1.70 +/- 0.11 和 1.72 +/- 0.12]， 2-DGP 在所有层中积累，如 2-DGP/PCr 所示（EPI、MID 和 ENDO 分别为 0.55 +/- 0.12、0.52 +/- 0.10 和 0.37 +/- 0.08；P < 0.05，EPI > ENDO）。在 IZ 中，湿重与干重之比与正常区域相比显着增加（5.9 +/- 0.5 与 4.4 +/- 0.4；P < 0.05）。因此，在狭窄灌注床中，在多巴酚丁胺诱导的高心脏做功状态期间，尽管血流量较高，但心外膜下层表现出更大的代谢变化，其特征是向更高的碳水化合物代谢转变，这表明对高心脏做功状态的稳态反应的特征是能量代谢中更多的葡萄糖利用。
The heterogeneity across the left ventricular wall is characterized by higher rates of oxygen consumption, systolic thickening fraction, myocardial perfusion, and lower energetic state in the subendocardial layers (ENDO). During dobutamine stimulation-induced demand ischemia, the transmural distribution of energy demand and metabolic markers of ischemia are not known. In this study, hemodynamics, transmural high-energy phosphate (HEP), 2-deoxyglucose-6-phosphate (2-DGP) levels, and myocardial blood flow (MBF) were determined under basal conditions, during dobutamine infusion (DOB: 20 mu g.kg(-1).min(-1) iv), and during coronary stenosis + DOB + 2-deoxyglucose (2-DG) infusion. DOB increased rate pressure products (RPP) and MBF significantly without affecting the subendocardial-to-subepicardial blood flow ratio (ENDO/EPI) or HEP levels. During coronary stenosis + DOB + 2-DG infusion, RPP, ischemic zone (IZ) MBF, and ENDO/EPI decreased significantly. The IZ ratio of creatine phosphate-to- ATP decreased significantly [2.30 +/- 0.14, 2.06 +/- 0.13, and 2.04 +/- 0.11 to 1.77 +/- 0.12, 1.70 +/- 0.11, and 1.72 +/- 0.12 for EPI, midmyocardial (MID), and ENDO, respectively], and 2-DGP accumulated in all layers, as evidenced by the 2-DGP/PCr (0.55 +/- 0.12, 0.52 +/- 0.10, and 0.37 +/- 0.08 for EPI, MID, and ENDO, respectively; P < 0.05, EPI > ENDO). In the IZ the wet weight-to-dry weight ratio was significantly increased compared with the normal zone (5.9 +/- 0.5 vs. 4.4 +/- 0.4; P < 0.05). Thus, in the stenotic perfused bed, during dobutamine-induced high cardiac work state, despite higher blood flow, the subepicardial layers showed the greater metabolic changes characterized by a shift toward higher carbohydrate metabolism, suggesting that a homeostatic response to high-cardiac work state is characterized by more glucose utilization in energy metabolism.