EFFECTS OF INOSINE ON GLYCOLYSIS AND CONTRACTURE DURING MYOCARDIAL-ISCHEMIA
EFFECTS OF INOSINE ON GLYCOLYSIS AND CONTRACTURE DURING MYOCARDIAL-ISCHEMIA
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DOI：
10.1161/01.res.68.2.578
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发表时间：
1991-02-01
影响因子：
20.1
通讯作者：
ROBERTS, R
中科院分区：
文献类型：
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作者：
LEWANDOWSKI, ED;JOHNSTON, DL;ROBERTS, R
在离体兔心上观察了肌苷（INO）对缺血心肌底物代谢和僵直形成的影响。 通过化学分析评估组织提取物中的代谢物含量，并通过C-13和P-31核磁共振光谱评估整个心脏中的代谢物含量。 在代谢[3-C-13]丙酮酸或[1-C-13]葡萄糖的缺血心脏中，1 mM INO增加总丙氨酸和C-13标记丙氨酸含量;乳酸含量不受影响。 在缺血3分钟时，用丙酮酸盐+ INO灌注的心脏中的组织丙氨酸为1.81 +/-0.11-μ-M/g湿重（平均值+/- SEM），而用丙酮酸盐单独灌注的心脏中的组织丙氨酸为1.23 +/-0.15-μ-M/g湿重（p < 0.05）。 INO减少组织糖原在缺血过程中，灌流心脏。 缺血心脏中供应葡萄糖+ INO的组织丙氨酸含量（1.29 +/- 0.13 μ M/g湿重）大于仅供应葡萄糖的缺血心脏中的组织丙氨酸含量（0.65 +/- 0.14 μ M/g湿重）。 丙氨酸被发现起源于丙酮酸，是葡萄糖灌注心脏中的糖酵解终产物。 INO提高了缺血、完整心脏中[3-C-13]丙氨酸/[3-C-13]乳酸的比值（葡萄糖= 0.24 +/- 0.07 vs葡萄糖+ INO = 0.60 +/- 0.09;丙酮酸= 0.49 +/- 0.08 vs丙酮酸+ INO = 0.89 +/- 0.08）。 在缺血7分钟时，葡萄糖+ INO的ATP含量降至70 +/-3%，而葡萄糖单独的ATP含量为58 +/-5%。 使用INO时，僵直（结石心）从14.7 +/- 1.3分钟延迟至23.2 +/- 1.6分钟。 INO没有改变缺血心脏中的ATP含量，这些心脏被供应丙酮酸，但延迟了僵直（丙酮酸= 9.9 +/- 1.2分钟;丙酮酸+ INO = 15.6 +/- 1.0分钟），可能是以糖原为代价的。 补充葡萄糖改善了INO与丙酮酸的有效性，以保护ATP（丙酮酸+葡萄糖= 42 +/- 6%;丙酮酸+葡萄糖+ INO = 72 +/- 6%）并进一步延迟僵硬（丙酮酸+葡萄糖= 13.3 +/- 1.5分钟;丙酮酸+葡萄糖+ INO = 20.3 +/- 1.8分钟）。 葡萄糖代谢支持INO治疗的缺血心脏的能量和收缩状态的改善。 因此，INO对缺血性心脏的心脏保护与功能完整性的保持和由于糖酵解活性增加而改善的能量产生有关。 在INO的存在下，糖酵解的活化通过增加丙氨酸的产生来调节，而没有乳酸的额外积累。
The effects of inosine (INO) on substrate metabolism and rigor formation in ischemic myocardium were examined in isolated rabbit hearts. Metabolite content was assessed in tissue extracts by chemical analysis and in the whole heart by C-13 and P-31 nuclear magnetic resonance spectroscopy. In ischemic hearts metabolizing either [3-C-13]pyruvate or [1-C-13]glucose, 1 mM INO increased both total and C-13-labeled alanine content; lactate content was unaffected. At 3 minutes of ischemia, tissue alanine was 1.81 +/- 0.11-mu-M/g wet wt (mean +/- SEM) in hearts perfused with pyruvate + INO versus 1.23 +/- 0.15-mu-M/g wet wt in hearts perfused with pyruvate alone (p < 0.05). INO reduced tissue glycogen during ischemia in pyruvate-perfused hearts. Tissue alanine content in ischemic hearts that were supplied glucose + INO (1.29 +/- 0.13-mu-M/g wet wt) was greater than in ischemic hearts supplied glucose alone (0.65 +/- 0.14-mu-M/g wet wt). Alanine was found to originate from pyruvate and was a glycolytic end product in glucose-perfused hearts. INO raised the [3-C-13]alanine/[3-C-13]lactate ratio in ischemic, intact hearts (glucose = 0.24 +/- 0.07 versus glucose + INO = 0.60 +/- 0.09; pyruvate = 0.49 +/- 0.08 versus pyruvate + INO = 0.89 +/- 0.08). At 7 minutes of ischemia, ATP content fell to 70 +/- 3% with glucose + INO versus 58 +/- 5% with glucose alone. Rigor (stone heart) was delayed from 14.7 +/- 1.3 to 23.2 +/- 1.6 minutes with INO. INO did not change ATP content in ischemic hearts that were supplied pyruvate but delayed rigor (pyruvate = 9.9 +/- 1.2 minutes; pyruvate + INO = 15.6 +/- 1.0 minutes), possibly at the expense of glycogen. Supplemental glucose improved the effectiveness of INO with pyruvate to preserve ATP (pyruvate + glucose = 42 +/- 6%; pyruvate + glucose + INO = 72 +/- 6%) and further delayed rigor (pyruvate + glucose = 13.3 +/- 1.5 minutes; pyruvate + glucose + INO = 20.3 +/- 1.8 minutes). Glucose metabolism supported improved energetic and contractile states in ischemic hearts treated with INO. Thus, cardioprotection of the ischemic heart by INO was associated with preservation of functional integrity and improved energy production due to increased glycolytic activity. Activation of glycolysis in the presence of INO was accommodated by augmented alanine production without the additional accumulation of lactate.