Nuclear Magnetic Resonance Studies of Cationic and Energetic Alterations With Oxidant Stress in the Perfused Heart
| Autor: | Martin M. Pike, S. Yanagida, Cameron S. Luo, Gerald M. Pohost, M. Doyle |
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| Rok vydání: | 1995 |
| Předmět: |
Male
Magnetic Resonance Spectroscopy Physiology Sodium chemistry.chemical_element medicine.disease_cause Rats Sprague-Dawley chemistry.chemical_compound Nuclear magnetic resonance medicine Animals Glycolysis Lactic Acid Pyruvates Ion transporter chemistry.chemical_classification Ion Transport Sugar phosphates Heart Rats Lactic acid Perfusion Oxidative Stress Cytosol chemistry Biochemistry Lactates Energy Metabolism Cardiology and Cardiovascular Medicine Oxidative stress Homeostasis |
| Zdroj: | Circulation Research. 77:773-783 |
| ISSN: | 1524-4571 0009-7330 |
| Popis: | Abstract The postischemic generation of oxygen-derived free radicals may contribute to myocardial reperfusion injury by affecting sarcolemmal ion transport. Recent evidence indicates that exposure to reactive oxygen intermediates induces rapid increases in myocardial cytosolic free Ca 2+ (Ca 2+ i ). The mechanism is undetermined but may involve disturbances in Na + homeostasis. We tested this hypothesis by interleaving 23 Na and 31 P nuclear magnetic resonance (NMR) measurements of Na + i and high-energy phosphates in glucose-perfused rat hearts exposed to hydroxyl radicals generated from H 2 O 2 and Fe 3+ . In separate experiments, K + i and Ca 2+ i were measured with 39 K and 19 F NMR, respectively. The hearts rapidly exhibited contracture. Threefold Na + i increases and substantial K + i depletion were observed. Glycolytic inhibition was indicated by rapid sugar phosphate accumulation and cellular energy depletion. Notably, however, severe functional and energetic deterioration and substantial elevation of Ca 2+ i occurred before substantial Na + i accumulation or K + i depletion was observed. Further experiments investigated the ability of pyruvate to scavenge H 2 O 2 and to protect the myocardium from oxidant stress. Pyruvate (1 or 2.5 mmol/L) dramatically attenuated functional and energetic alterations and alterations in Na + i and K + i , whereas acetate (2.5 mmol/L) offered no protection. Unlike pyruvate, lactate (5 mmol/L) has little or no capacity to scavenge H 2 O 2 but has similar protective effects. In conclusion, pyruvate effectively protects against H 2 O 2 /Fe 3+ , largely by direct H 2 O 2 scavenging. Protection with lactate may involve intracellular pyruvate augmentation. Without exogenous pyruvate or lactate, myocardial Na + homeostasis can be substantially altered by oxidant stress, possibly via cellular energy depletion. Excess Na + i accumulation may, in turn, hasten metabolic and functional deterioration, but a causal link with the initial alterations in function or Ca 2+ i was not supported. |
| Databáze: | OpenAIRE |
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