2002 Fiscal Year Final Research Report Summary
Intracellular mechanism of opioids on myocardial contraction
| Project/Area Number |
12671487
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Sapporo Medical University School of Medicine |
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Principal Investigator |
KANAYA Noriaki Sapporo Medical University School of Medicine, Anesthesiology, Assistant Professor, 医学部, 講師 (10244344)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAYAMA Masayasu Sapporo Medical University School of Medicine, Anesthesiology, Instructor, 医学部, 助手 (60336401)
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| Project Period (FY) |
2000 – 2002
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| Keywords | Heart / Opioid / calcium |
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| Research Abstract |
Freshly isolated rat ventricular myocytes were loaded with the Ca^<2+> indicator, fura-2, at 37℃ for 20 min. Intracellular Ca^<2+> transients and myocyte shortening were simultaneously monitored. Addition of fentanyl (30-1000 nM) resulted in dose-dependent decreases in both peak Ca^<2+>, and myocyte shortening. Morphine (3-100 μM) caused a decrease in myocyte shortening without any concomitant decreases in Ca^<2+> transient. Morphine, but not fentanyl, decreased the amount of Ca^<2+> released from intracellular stores in response to caffeine. Both fentanyl (100 nM) and morphine (10 μM) showed a rightward shift in the dose-response curve to extracellular Ca^<2+> for shortening, with no concomitant effect on the intracellular Ca^<2+> transient. These results indicate that fentanyl and morphine have a direct negative inotropic effect on cardiac excitation contraction coupling at the cellular level. Fentanyl, but not morphine, causes a myocardial depression which is mediated by a decrease in the availability of intracellular free Ca^<2+>. Fentanyl may also alter sarcoplasmic reticulum Ca^<2+> handling and decrease myofilament Ca^<2+> sensitivity, as suggested by changes in the timing of the contractile parameters and the rightward shift in the dose-response curve to extracellular Ca^<2+>, respectively. In contrast, morphine causes a myocardial depression mainly mediated by a decrease in myofilament responsiveness to Ca^<2+>.
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