Alterations of Intracellular Calcium Homeostasis and Myocardial Energetics in Acute Adriamycin-Induced Heart Failure
| Autor: | Hiroyuki Suga, Hideo Kusuoka, Takenobu Kamada, Shiho Futaki, Akira Kitabatake, Yukihiro Koretsune, Michitoshi Inoue |
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| Rok vydání: | 1991 |
| Předmět: |
Male
medicine.medical_specialty Magnetic Resonance Spectroscopy Phosphocreatine chemistry.chemical_element In Vitro Techniques Calcium Biology Calcium in biology Phosphates chemistry.chemical_compound Adenosine Triphosphate BAPTA Internal medicine medicine Animals Homeostasis Egtazic Acid Heart Failure Pharmacology Calcium metabolism Myocardium Ferrets Heart Endocrinology chemistry Doxorubicin Energy Metabolism Cardiology and Cardiovascular Medicine Perfusion Intracellular |
| Zdroj: | Journal of Cardiovascular Pharmacology. 18:437-444 |
| ISSN: | 0160-2446 |
| DOI: | 10.1097/00005344-199109000-00017 |
| Popis: | To elucidate the mechanism of acute contractile failure induced by adriamycin, the intracellular concentrations of free calcium ([Ca2+]i) and energy-related phosphate compounds were determined in isolated ferret hearts. The time-averaged [Ca2+]i was measured at 10 min resolution using fluorine nuclear magnetic resonance (NMR) spectroscopy and the NMR-sensitive Ca2+ indicator 5F-BAPTA. [Ca2+]i significantly increased from a control of 381 +/- 66 nM (mean +/- SEM, N = 5) to 789 +/- 171 nM during 30 min of perfusion with adriamycin (30 mg/L), and remained elevated for at least 30 min after washout. The isovolumic LV pressure decreased to 80.7 +/- 8.9% of control (N = 12, p less than 0.05) and did not recover after washout. Intramyocardial contents of energy-related phosphates were determined by phosphorus NMR spectroscopy in seven other hearts. No significant change in myocardial energy metabolism was observed during adriamycin exposure and after washout; inorganic phosphate did not increase, and phosphocreatine and ATP did not decrease. These results indicate that Ca overload induced by adriamycin is associated with acute contractile failure. Adriamycin has been reported to inhibit Na-Ca exchange and to affect the gating of Ca2+ release channels in sarcoplasmic reticulum. Whatever the cause of the calcium overload, the fact that dysfunction persists as an aftereffect of adriamycin is consistent with the hypothesis that calcium overload, in the absence of ischemia, can leave behind long-lasting contractile dysfunction. |
| Databáze: | OpenAIRE |
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