Aasum E, Steigen T K, Larsen T S
Department of Medical Physiology, Institute of Medical Biology, University of Tromso, Norway.
J Mol Cell Cardiol. 1997 Feb;29(2):527-34. doi: 10.1006/jmcc.1996.0296.
In the present study we examined the impact of glycolysis and glucose oxidation on myocardial calcium control and mechanical function of fatty acid-perfused rat hearts subjected to hypothermia rewarming. One group (control) was given glucose (11.1 mM) and palmitate (1.2 mM) as energy substrates. In a second group glycolysis was inhibited by iodoacetate (IAA, 100 microM) and replacement of glucose with pyruvate (5 mM), whereas in the third group glucose oxidation was stimulated by administration of dichloroacetate (DCA, 1 mM) and insulin (500 microU/ml). All groups showed a rise in myocardial calcium ([Ca]total in response to hypothermia (10 degrees C). However, [Ca]total was significantly lower both in IAA- and DCA-treated hearts, as compared to controls (2.20 +/- 0.22 and 2.94 +/- 0.20 v 3.83 +/- 0.29 nmol/mg dry wt., P < 0.025). The reduced calcium load in the treated hearts was correlated with higher levels of high energy phosphates. Following rewarming control and DCA-treated hearts still showed elevated [Ca]total, whereas IAA-treated hearts [Ca]total was not different from the pre-hypothermic value. All groups showed a reduction in cardiac output following rewarming. Furthermore, the control group, in contrast to both IAA- and DCA-treated hearts, showed a significant reduction in systolic pressure. These results show that hypothermia-induced calcium uptake in glucose and fatty acid-perfused rat hearts was reduced by two different metabolic approaches: (1) inhibition of glycolysis by IAA while simultaneously by-passing the glycolytic pathway by exogenous pyruvate: and (2) stimulation of glucose oxidation by DCA. Thus, glycolytic ATP is not an essential regulator of sarcolemmal calcium transport under the present experimental conditions. Instead, we suggest that a change in oxidative substrate utilization in favour of carbohydrates may improve myocardial calcium homeostasis during hypothermia and rewarming.
在本研究中，我们检测了糖酵解和葡萄糖氧化对低温复温的脂肪酸灌注大鼠心脏的心肌钙调控和机械功能的影响。一组（对照组）给予葡萄糖（11.1 mM）和棕榈酸酯（1.2 mM）作为能量底物。第二组用碘乙酸盐（IAA，100 μM）抑制糖酵解并用丙酮酸（5 mM）替代葡萄糖，而第三组通过给予二氯乙酸盐（DCA，1 mM）和胰岛素（500 μU/ml）刺激葡萄糖氧化。所有组在低温（10℃）时心肌钙（[Ca]总量）均升高。然而，与对照组相比，IAA处理组和DCA处理组心脏的[Ca]总量均显著降低（分别为2.20±0.22和2.94±0.20对3.83±0.29 nmol/mg干重，P<0.025）。处理组心脏中钙负荷的降低与高能磷酸盐水平升高相关。复温后，对照组和DCA处理组心脏的[Ca]总量仍升高，而IAA处理组心脏的[Ca]总量与低温前值无差异。所有组复温后心输出量均降低。此外，与IAA处理组和DCA处理组心脏相反，对照组收缩压显著降低。这些结果表明，低温诱导的葡萄糖和脂肪酸灌注大鼠心脏中的钙摄取可通过两种不同的代谢方法降低：（1）用IAA抑制糖酵解，同时通过外源性丙酮酸绕过糖酵解途径；（2）用DCA刺激葡萄糖氧化。因此，在本实验条件下，糖酵解产生的ATP不是肌膜钙转运的必需调节因子。相反，我们认为有利于碳水化合物的氧化底物利用变化可能会改善低温和复温期间的心肌钙稳态。
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