We have developed and characterized a model of isoproterenol (ISO)-induced myocardial necrosis, identifying three stages of cardiac damage: a pre-infarction (0–12 h), infarction (24 h), and post-infarction period (48–96 h). Using this model, we have previously found alterations in calcium homeostasis and their relationship with oxidant stress in mitochondria, which showed deficient oxygen consumption and coupled ATP synthesis. Therefore, the present study was aimed at assessing the mitochondrial ability to transport and oxidize cytoplasmic reducing equivalents (NADH), correlating the kinetic parameters of the malate-aspartate shuttle, oxidant stress, and mitochondrial functionality. Our results showed only discreet effects during the cardiotoxic ISO action on the endogenous malate-aspartate shuttle activity, suggesting that endogenous mitochondrial NADH oxidation capacity (Nohl dehydrogenase) was not affected by the cellular stress. On the contrary, the reconstituted system showed significant enhancement in maximal capacity of the malate-aspartate shuttle activity only at later times (post-infarction period), probably as a compensatory part of cardiomyocytes’ response to the metabolic and functional consequences of the infarcted tissue. Therefore, these findings support the notion that heart damage associated with myocardial infarction suffers a set of sequential biochemical and metabolic modifications within cardiomyocytes, where mitochondrial activity, controlling the redox state, could play a relevant role.

中文翻译：

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异丙肾上腺素诱导的大鼠心肌梗死氧化应激开始时细胞质还原当量的线粒体氧化

我们开发并表征了异丙肾上腺素 (ISO) 诱导的心肌坏死模型，确定了心脏损伤的三个阶段：梗塞前 (0-12 小时)、梗塞 (24 小时) 和梗塞后 (48-96 小时) H）。使用该模型，我们之前已经发现钙稳态的改变及其与线粒体中氧化应激的关系，这表明氧消耗不足和耦合 ATP 合成。因此，本研究旨在评估线粒体转运和氧化细胞质还原当量 (NADH) 的能力，将苹果酸-天冬氨酸穿梭的动力学参数、氧化应激和线粒体功能相关联。我们的结果表明，在心脏毒性 ISO 作用期间，对内源性苹果酸-天冬氨酸穿梭活动仅产生谨慎影响，表明内源性线粒体 NADH 氧化能力（Nohl 脱氢酶）不受细胞应激的影响。相反，重建的系统仅在后期（梗塞后时期）显示出苹果酸-天冬氨酸穿梭活动的最大容量显着增强，这可能是心肌细胞对梗塞组织的代谢和功能后果的反应的代偿部分. 因此，这些发现支持这样一种观点，即与心肌梗塞相关的心脏损伤在心肌细胞内经历了一系列连续的生化和代谢改变，其中控制氧化还原状态的线粒体活动可能发挥相关作用。重建的系统仅在后期（梗塞后时期）显示出苹果酸-天冬氨酸穿梭活动的最大能力显着增强，这可能是心肌细胞对梗塞组织的代谢和功能后果的反应的代偿部分。因此，这些发现支持这样一种观点，即与心肌梗塞相关的心脏损伤在心肌细胞内经历了一系列连续的生化和代谢改变，其中控制氧化还原状态的线粒体活动可能发挥相关作用。重建的系统仅在后期（梗塞后时期）显示出苹果酸-天冬氨酸穿梭活动的最大能力显着增强，这可能是心肌细胞对梗塞组织的代谢和功能后果的反应的代偿部分。因此，这些发现支持这样一种观点，即与心肌梗塞相关的心脏损伤在心肌细胞内经历了一系列连续的生化和代谢改变，其中控制氧化还原状态的线粒体活动可能发挥相关作用。