Lüss Hartmut, Schäfers Michael, Neumann Joachim, Hammel Dieter, Vahlhaus Christian, Baba Hideo A, Janssen Frauke, Scheld Hans H, Schober Otmar, Breithardt Günter, Schmitz Wilhelm, Wichter Thomas
Institute of Pharmacology and Toxicology, Hospital of the Westfälische Wilhelms-Universität, Domagkstrasse 12, Münster, Germany.
Cardiovasc Res. 2002 Dec;56(3):411-21. doi: 10.1016/s0008-6363(02)00596-5.
Myocardial hibernation and stunning are characterized by depressed cardiac function in the presence of reduced or normal coronary blood flow. The underlying biochemical mechanisms are widely unknown and only limited data are available in human hearts.
Left ventricular transmural myocardial biopsies were obtained from normal and dysfunctional segments of patients undergoing coronary bypass surgery. Segments were classified as hibernating (n=10) or stunned (n=9) using contrast ventriculography and echocardiography, single photon emission computed tomography (SPECT), and positron emission tomography (PET). In each patient, biopsies from normal myocardial segments were used as controls (n=19). Compared to control myocardium, levels of cAMP (3'-5'cyclic adenosine monophosphate, in fmol/mg wet weight, means+/-S.E.M.) were higher in hibernating (673+/-76 versus 518+/-47, P<0.05) but unchanged in stunned myocardium (513+/-73 versus 466+/-97, P>0.05). Protein expression of phospholamban, sarcoendoplasmic Ca(2+)-ATPase 2a, calsequestrin, the inhibitory subunit of troponin, as well as the activation of p38 MAP kinase were not different when compared to controls. However, heat shock protein 72 (Hsp72) was increased 55% in stunned (2.89+/-0.58 versus 1.86+/-0.32, P<0.05) but not in hibernating myocardium (1.68+/-0.34 versus 1.67+/-0.29, P>0.05).
The data from the present study suggest different pathophysiological mechanisms for myocardial hibernation and stunning. Alterations in the homeostasis of cAMP might be a compensatory mechanism in myocardial hibernation, whereas expression of Hsp72 appears to be cardioprotective in human myocardial stunning. Future studies should further elucidate these mechanisms and their potential impact on future therapeutic interventions.
心肌冬眠和心肌顿抑的特征是在冠状动脉血流减少或正常的情况下心脏功能降低。其潜在的生化机制尚不明确，在人体心脏方面仅有有限的数据。
从接受冠状动脉搭桥手术患者的正常和功能异常节段获取左心室透壁心肌活检样本。使用对比心室造影、超声心动图、单光子发射计算机断层扫描（SPECT）和正电子发射断层扫描（PET）将节段分为冬眠心肌（n = 10）或顿抑心肌（n = 9）。在每位患者中，取自正常心肌节段的活检样本用作对照（n = 19）。与对照心肌相比，冬眠心肌中cAMP（3'-5'环磷酸腺苷，fmol/mg湿重，均值±标准误）水平较高（673±76对518±47，P<0.05），而顿抑心肌中cAMP水平无变化（513±73对466±97，P>0.05）。与对照相比，受磷蛋白、肌浆网Ca(2 +)-ATP酶2a、肌钙蛋白抑制亚基的蛋白表达以及p38丝裂原活化蛋白激酶的激活无差异。然而，热休克蛋白72（Hsp72）在顿抑心肌中增加了55%（2.89±0.58对1.86±0.32，P<0.05），而在冬眠心肌中未增加（1.68±0.34对1.67±0.29，P>0.05）。
本研究数据提示心肌冬眠和顿抑存在不同的病理生理机制。cAMP稳态的改变可能是心肌冬眠中的一种代偿机制，而Hsp72的表达似乎对人体心肌顿抑具有心脏保护作用。未来研究应进一步阐明这些机制及其对未来治疗干预的潜在影响。
