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哺乳动物心肌中的无氧能量产生与收缩活动。

Anoxic energy production and contractile activity in mammalian cardiac muscle.

作者信息

Siess M, Seifart H I

出版信息

Adv Myocardiol. 1980;2:295-310.

PMID:7423046
Abstract

Contractile activity of electrically driven left atria of guinea pigs was measured auxotonically under normoxic and anoxic conditions at various frequencies and temperatures in Krebs-Henseleit solution containing 15 mM glucose. At 35 degrees C, a frequency of 0.5 Hz and anoxia ("anoxia test") reduced contractile activity was observed, lasting 6.6 +/- 1.55 hr. Under normoxic conditions at 0.5 Hz and 35 degrees C the contractile work per beat (cwb) amounts to 35% of the maximum reached at 1.5 Hz, according to the force-frequency relationship. The total contractile work per hr only comes up to 5% of the maximum reached at 4.0 Hz. The oxygen consumption at 0.5 Hz only exceeds the value of resting atria by 10%. A positive inotropic peak of short duration observed directly after acute anoxia can be antagonized by beta-receptor blockade. Then contractile activity decreases during the first half hr of anoxia to around 20%-30% of the initial value under oxygen. In the second phase, the reduced contractile activity recovers and is stabilized at a level between 50%-80% of the control value during the first and second hour of anoxia and then decreases slowly during the following hours. The recovery period of anoxic contractile activity coincides with the time-dependent increase of the lactic acid production rate which reaches a maximum after around 1 hr of anoxia. This can also explain why the rapid decrease of ATP (30%) and creatine phosphate (CP) (90%) during the first 20 min is stabilized at this reduced value during the 2 hr of anoxia studied. Related to the measured oxygen consumption during normoxia, the glucose consumption increases during anoxia in resting atria approximately 300% and, in beating atria, approximately 650%, representing an ATP production rate of approximately 20% and approximately 50%, respectively, related to aerobic conditions. G-strophanthin enhances anoxic contractile activity up to 200% of the aerobic initial control value and prolongs the anoxic tolerance from 6.6 +/- 1.55 to 21.2 +/- 3.3 hr without significant additional increase of glycolysis or a further decrease of energy-rich phosphates. Addition of adenine and ribose as precursors of the adenine nucleotide pool during the first and second hours of anoxia increases anoxic contractile activity and avoids loss of ATP, ADP, and CP, without enhancemnt of glycolysis. The importance of these findings for anoxic survival of cardiac tissue is discussed. This "anoxia test" can be used to check influence on: 1) force and duration of anoxic contractile activity as well as anoxic arrhythmias (anoxic energy consumption), 2) the rate of anaerobic glycolysis (anoxic energy production), and 3) the concentration of energy-rich phosphates (energy storage).

摘要

在含有15 mM葡萄糖的克雷布斯 - 亨泽莱特溶液中,在常氧和缺氧条件下,于不同频率和温度下,对豚鼠电驱动左心房的收缩活动进行了辅助张力测量。在35℃时,观察到频率为0.5 Hz且缺氧(“缺氧试验”)时收缩活动降低,持续6.6±1.55小时。根据力 - 频率关系,在常氧条件下,0.5 Hz和35℃时每搏收缩功(cwb)相当于1.5 Hz时达到的最大值的35%。每小时的总收缩功仅为4.0 Hz时达到的最大值的5%。0.5 Hz时的耗氧量仅比静息心房的值高10%。急性缺氧后立即观察到的短暂正性肌力峰值可被β受体阻滞剂拮抗。然后,在缺氧的前半小时内,收缩活动降至氧气条件下初始值的20% - 30%左右。在第二阶段,降低的收缩活动恢复,并在缺氧的第一和第二小时稳定在对照值的50% - 80%之间的水平,然后在接下来的几个小时内缓慢下降。缺氧收缩活动的恢复期与乳酸产生率随时间的增加相吻合,乳酸产生率在缺氧约1小时后达到最大值。这也可以解释为什么在研究的2小时缺氧过程中,ATP(30%)和磷酸肌酸(CP)(90%)在前20分钟内的快速下降在该降低值处稳定下来。与常氧期间测量的耗氧量相关,缺氧时静息心房的葡萄糖消耗增加约300%,跳动心房的葡萄糖消耗增加约650%,分别相当于有氧条件下ATP产生率约为20%和约50%。毒毛花苷将缺氧收缩活动增强至有氧初始对照值的200%,并将缺氧耐受性从6.6±1.55小时延长至21.2±3.3小时,而不会显著额外增加糖酵解或进一步降低高能磷酸盐。在缺氧的第一和第二小时添加腺嘌呤和核糖作为腺嘌呤核苷酸池的前体,可增加缺氧收缩活动并避免ATP、ADP和CP的损失,而不会增强糖酵解。讨论了这些发现对心脏组织缺氧存活的重要性。这种“缺氧试验”可用于检查对以下方面的影响:1)缺氧收缩活动的力量和持续时间以及缺氧性心律失常(缺氧能量消耗),2)无氧糖酵解速率(缺氧能量产生),3)高能磷酸盐浓度(能量储存)。

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