McNulty P H, Jagasia D, Cline G W, Ng C K, Whiting J M, Garg P, Shulman G I, Soufer R
Sections of Cardiovascular Medicine, Connecticut VA Medical Center, Yale University School of Medicine, New Haven, CT 06510, USA.
Circulation. 2000 Feb 29;101(8):917-22. doi: 10.1161/01.cir.101.8.917.
Rapid reperfusion of an occluded coronary artery salvages regional mechanical function, but this benefit may not be realized for hours or days because of postischemic stunning. Recovery from stunning is incompletely understood but may involve adaptive changes in heart glucose metabolism.
To examine whether reversible coronary occlusion produces sustained changes in regional glucose metabolism in vivo, we performed a 20-minute left coronary artery occlusion followed by 24 hours of open-artery reperfusion in intact rats. Coronary occlusion produced stunning of the anterolateral left ventricle that resolved over 24 hours. When examined at 24 hours, reperfused regions were fully contractile and viable by vital staining and microscopy but demonstrated 25% reduction in blood flow and 50% increased uptake of circulating glucose, as estimated by in vivo [(13)N]NH(3) and [(18)F]fluorodeoxyglucose (FDG) tracer uptake. Reperfused regions had largely inactive glycogen synthase, low rates of glycogen synthesis, and persistent 50% glycogen depletion but increased flux of plasma [1-(13)C]glucose into myocardial [3-(13)C]alanine, indicating preferential shunting of imported glucose away from storage and into glycolysis.
Sustained increases in regional glycolytic consumption of circulating glucose occur during reperfusion of a limited-duration coronary occlusion. This suggests a role for glycolytic ATP in the recovery from postischemic stunning in vivo. Furthermore, [(13)N]NH(3) /FDG regional mismatch may constitute a clinically accessible late metabolic signature of regional myocardial ischemia.
闭塞冠状动脉的快速再灌注可挽救局部机械功能，但由于缺血后心肌顿抑，这种益处可能在数小时或数天内无法实现。心肌顿抑的恢复机制尚不完全清楚，但可能涉及心脏葡萄糖代谢的适应性变化。
为了研究可逆性冠状动脉闭塞是否会在体内引起局部葡萄糖代谢的持续变化，我们对完整大鼠进行了20分钟的左冠状动脉闭塞，随后进行24小时的开放动脉再灌注。冠状动脉闭塞导致左心室前外侧心肌顿抑，在24小时内逐渐恢复。在24小时时进行检查，再灌注区域通过活体染色和显微镜检查显示完全收缩且存活，但血流量减少了25%，循环葡萄糖摄取增加了50%，这是通过体内[(13)N]NH(3)和[(18)F]氟脱氧葡萄糖（FDG）示踪剂摄取估计得出的。再灌注区域的糖原合酶基本无活性，糖原合成率低，糖原持续耗竭50%，但血浆[1-(13)C]葡萄糖向心肌[3-(13)C]丙氨酸的通量增加，表明输入的葡萄糖优先从储存转向糖酵解。
在有限时长冠状动脉闭塞再灌注期间，局部循环葡萄糖的糖酵解消耗持续增加。这表明糖酵解产生的ATP在体内缺血后心肌顿抑的恢复中起作用。此外，[(13)N]NH(3)/FDG局部不匹配可能构成临床上可检测到的局部心肌缺血的晚期代谢特征。
