Department of Medicine, University of Minnesota Medical School, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
Am J Physiol Heart Circ Physiol. 2011 Mar;300(3):H836-44. doi: 10.1152/ajpheart.00540.2010. Epub 2010 Dec 3.
We previously reported that the myocardial energetic state, as defined by the ratio of phosphocreatine to ATP (PCr/ATP), was preserved at baseline (BL) in a swine model of chronic myocardial ischemia with mild reduction of myocardial blood flow (MBF) 10 wk after the placement of an external constrictor on the left anterior descending coronary artery. It remains to be seen whether this stable energetic state is maintained at a longer-term follow-up. Hibernating myocardium (HB) was created in minipigs (n = 7) by the placement of an external constrictor (1.25 mm internal diameter) on the left anterior descending coronary artery. Function was assessed with MRI at regular intervals until 6 mo. At 6 mo, myocardial energetic in the HB was assessed by (31)P-magnetic resonance spectrometry and myocardial oxygenation was examined from the deoxymyoglobin signal using (1)H-magnetic resonance spectrometry during BL, coronary vasodilation with adenosine, and high cardiac workload with dopamine and dobutamine (DpDb). MBF was measured with radiolabeled microspheres. At BL, systolic thickening fraction was significantly lower in the HB compared with remote region (34.4 ± 9.4 vs. 50.1 ± 10.7, P = 0.006). This was associated with a decreased MBF in the HB compared with the remote region (0.73 ± 0.08 vs. 0.97 ± 0.07 ml · min(-1) · g, P = 0.03). The HB PCr/ATP at BL was normal. DpDb resulted in a significant increase in rate pressure product, which caused a twofold increase in MBF in the HB and a threefold increase in the remote region. The systolic thickening fraction increased with DpDb, which was significantly higher in the remote region than HB (P < 0.05). The high cardiac workload was associated with a significant reduction in the HB PCr/ATP (P < 0.02), but this response was similar to normal myocardium. Thus HB has stable BL myocardial energetic despite the reduction MBF and regional left ventricular function. More importantly, HB has a reduced contractile reserve but has a similar energetic response to high cardiac workload like normal myocardium.
我们之前报道称，在放置左前降支冠状动脉外部缩窄器 10 周后，猪慢性心肌缺血模型中，磷酸肌酸与三磷酸腺苷（PCr/ATP）的比值定义的心肌能量状态在基线（BL）时保持不变，心肌血流（MBF）轻度减少。尚不清楚这种稳定的能量状态是否能在更长期的随访中保持。通过在左前降支冠状动脉上放置外部缩窄器（内径 1.25 毫米），在小型猪中创建冬眠心肌（HB）。通过 MRI 定期评估功能，直至 6 个月。在 6 个月时，通过（31）P 磁共振波谱评估 HB 中的心肌能量，并在 BL、腺苷引起的冠状动脉扩张以及多巴胺和多巴酚丁胺（DpDb）引起的高心脏负荷期间，使用（1）H 磁共振波谱检查脱氧肌红蛋白信号评估心肌氧合。使用放射性标记微球测量 MBF。BL 时，与远隔区相比，HB 的收缩增厚分数明显较低（34.4 ± 9.4 比 50.1 ± 10.7，P = 0.006）。这与 HB 与远隔区相比，MBF 减少有关（0.73 ± 0.08 比 0.97 ± 0.07 ml·min-1·g，P = 0.03）。BL 时 HB 的 PCr/ATP 正常。DpDb 导致心率血压乘积显著增加，导致 HB 的 MBF 增加两倍，远隔区增加三倍。DpDb 使收缩增厚分数增加，远隔区明显高于 HB（P <0.05）。高心脏负荷与 HB 的 PCr/ATP 显著降低有关（P <0.02），但这种反应与正常心肌相似。因此，尽管 MBF 和区域性左心室功能降低，HB 仍具有稳定的 BL 心肌能量。更重要的是，HB 的收缩储备减少，但对高心脏负荷的能量反应与正常心肌相似。
