Griese M, Perlitz V, Jüngling E, Kammermeier H
Department of Physiology, Medical Faculty, RWTH Aachen, FRG.
J Mol Cell Cardiol. 1988 Dec;20(12):1189-201. doi: 10.1016/0022-2828(88)90598-6.
The effects of graded hypoxia, graded reoxygenation after anoxic perfusion and of different extracellular K+-concentrations on cardiac energy metabolism and performance were studied in isolated, perfused, electrically paced rat hearts. Graded hypoxia was induced by different oxygen partial pressure (PO2: 736 to 43 mmHg, nine intermediate steps; O2 supply: (AVDCF): 300 to 21 microliters/gmin) in perfusate for 3 min, thus leading to different levels of relative mechanical steady state. Evaluated free energy change of ATP-hydrolysis (dG/d zeta) decreased largely in parallel with peak systolic pressure (Psyst) and systolic dP/dtmax, whereas diastolic dP/dtmin declined already to lowest values with moderate hypoxia. For regular beats and beats potentiated by paired stimulation the same relationships were found. Complete reoxygenation of hearts perfused anoxically beforehand (10 or 30 min, PO2 less than 6 mmHg), restored Psyst and dG/d zeta completely. Graded reoxygenation from different levels of hypoxia resulted in restitution of dG/d zeta and Psyst to the same levels as in graded hypoxia. The inotropic effect of paired stimulation was moderately reduced. Cytosolic Pi-levels remained increased during partial reoxygenation and exhibited no distinct relationship with mechanical performance. High extracellular K+ (13.5 mM) resulted in increased Psyst and elevated dG/d zeta-levels. Cardiac failure during graded hypoxia and high K+ occurred at comparatively high dG/d zeta levels. Reoxygenation with high K+, led to recovery of dG/d zeta levels but not of Psyst values. According to the results obtained in early hypoxic failure free energy dependence of Na+/K+-ATPase is of minor relevance whereas free energy dependence of sarcoplasmic Ca2+ regulating processes appears to be important.
在离体、灌注、电起搏的大鼠心脏中，研究了分级低氧、缺氧灌注后的分级复氧以及不同细胞外钾离子浓度对心脏能量代谢和功能的影响。通过在灌注液中设置不同的氧分压（PO₂：736至43 mmHg，九个中间步骤；氧气供应：(AVD*CF)：300至21微升/克·分钟）诱导分级低氧3分钟，从而导致不同水平的相对机械稳态。评估的ATP水解自由能变化（dG/dζ）在很大程度上与收缩压峰值（Psyst）和收缩期dP/dtmax平行下降，而舒张期dP/dtmin在中度低氧时就已降至最低值。对于正常搏动和成对刺激增强的搏动，发现了相同的关系。预先进行缺氧灌注（10或30分钟，PO₂小于6 mmHg）的心脏完全复氧后，Psyst和dG/dζ完全恢复。从不同低氧水平进行分级复氧导致dG/dζ和Psyst恢复到分级低氧时的相同水平。成对刺激的正性肌力作用适度降低。在部分复氧期间，胞质无机磷水平持续升高，且与机械性能无明显关系。高细胞外钾（13.5 mM）导致Psyst升高和dG/dζ水平升高。分级低氧和高钾期间的心力衰竭发生在相对较高的dG/dζ水平。高钾复氧导致dG/dζ水平恢复，但Psyst值未恢复。根据早期低氧性心力衰竭的研究结果，Na⁺/K⁺-ATP酶的自由能依赖性相关性较小，而肌浆网Ca²⁺调节过程的自由能依赖性似乎很重要。
