Tanonaka K, Niwa T, Takeo S
Department of Pharmacology, Tokyo University of Pharmacy and Life Science, Japan.
Jpn Heart J. 1996 Jan;37(1):105-17. doi: 10.1536/ihj.37.105.
The present study was undertaken to determine whether myocardial energy or ion levels are related to oxygen-replenishment-induced recovery of cardiac contractile force after hypoxia. Isolated rat hearts were perfused for 3 to 40 min under hypoxic conditions, followed by 45 min of reoxygenation. Hypoxia induced a cessation of cardiac contractile force, a rise in resting tension, a decrease in high energy phosphates, and an increase in lactate. Myocardial ATP, creatine phosphate (CP) and lactate reached steady-state levels after 15, 10 and 5 min of hypoxia, respectively. Hypoxic conditions in the present study also caused an increase in sodium content and a decrease in potassium content, but not changes in calcium content, along with a prolonged hypoxic period. When the hearts were perfused for more than 25 min under hypoxic conditions, no recovery of contractile force was observed following 45-min of reoxygenation. Hypoxic perfusion for more than 25 min induced an accumulation of tissue sodium content approximately 3 fold higher than the pre-hypoxic value at the end of hypoxia, and also induced a marked increase in myocardial calcium content upon reoxygenation. When tissue sodium content accumulated by less than 300% of the pre-hypoxic value, cardiac contractile function was partially reversed by reoxygenation and calcium-overload was not observed. The recovery of post-hypoxic cardiac contractility correlated with tissue sodium content during hypoxia rather than with myocardial high energy phosphate content at the end of hypoxia. These results suggest that accumulation of tissue sodium content in the hypoxic myocardium and calcium content in the reoxygenated myocardium may be indicative of hypoxia/reoxygenation-induced cardiac contractile failure.
本研究旨在确定心肌能量或离子水平是否与缺氧后氧补充诱导的心脏收缩力恢复有关。将离体大鼠心脏在缺氧条件下灌注3至40分钟，然后再进行45分钟的复氧。缺氧导致心脏收缩力停止、静息张力升高、高能磷酸盐减少以及乳酸增加。心肌ATP、磷酸肌酸（CP）和乳酸分别在缺氧15、10和5分钟后达到稳态水平。本研究中的缺氧条件还导致钠含量增加和钾含量减少，但钙含量没有变化，同时缺氧时间延长。当心脏在缺氧条件下灌注超过25分钟时，在45分钟的复氧后未观察到收缩力的恢复。超过25分钟的缺氧灌注导致组织钠含量在缺氧结束时比缺氧前的值积累约3倍，并且在复氧时还导致心肌钙含量显著增加。当组织钠含量积累低于缺氧前值的300%时，复氧可部分逆转心脏收缩功能，且未观察到钙超载。缺氧后心脏收缩力的恢复与缺氧期间的组织钠含量相关，而不是与缺氧结束时的心肌高能磷酸盐含量相关。这些结果表明，缺氧心肌中组织钠含量的积累和复氧心肌中钙含量的增加可能表明缺氧/复氧诱导的心脏收缩功能衰竭。
