Adriamycin Causes Dual Inotropic Effects Through Complex Modulation of Myocardial Ca^<2+> Handling

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• Effects of adriamycin(ADR) on the twitch contraction of isolated guinea pig cardiac muscles were examined to elucidate its actions on intracellular Ca^<2+> mobilization. In right ventricular papillary muscles, ADR (100-300μmol/L) caused positive inotropy when the muscles were constantly stimulated at low frequencies (0.1-0.5 Hz), whereas it caused negative inotropy when the muscles were stimulated at higher frequencies (2.0-3.0 Hz). Action potential duration was prolonged significantly by ADR, especially at the lower frequencies. The potentiation of twitch contraction of the first beat (B1) following a short rest period (2-10 s) in ventricular muscles was inhibited by ADR. In untreated papillary muscles, B1 contraction showed time-dependent decay in response to a prolongation of the preceding rest period up to 120 s. ADR (300μmol/L) caused ryanodin-like acceleration for the early B1 decay with rest period less than 20 s, but a substantial deceleration for the later B1 decay (≥30 s). In left atrial muscles stimulated constantly, ADR had significant negative inotropy throughout the entire range of stimulation frequencies tested (0.1-4.0 Hz). The post-rest potentiation of B1 contraction of atrial muscle in the presence of nifedipine was also inhibited by ADR. These findings suggest that ADR has dual inotropic effects through a complex modulation of myocardial Ca^<2+> handling, which may involve (1) an increase of Ca^<2+> influx through a prolongation of action potential duration, (2) ryanodine-like inhibition of Ca^<2+> release from the sarcoplasmic reticulum, and (3) inhibition of sarcolemmal Ca^<2+> extrusion probably through the Na^+/ Ca^<2+> exchange.

• 社団法人日本循環器学会の論文
• 1999-12-20

著者

• Kodama Itsuo

  Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya Universi

• Matsushita Toyoaki

  Department Of Cardiology Nagoya University Graduate School Of Medicine

• Matsushita Toyoaki

  Department Of Internal Medicine Aichi-gakuin School Of Dentistry

• ITOH MAKOTO

  First Department of Internal Medicine, Nagoya City University Medical School

• Matsushita Toyoaki

  Department Of Cardiology Nagoya University Graduate Shool Of Medicine

• Takamatsu Junki

  Department Of Transfusion Medicine Cardiology And Hematology Nagoya University Hospital

• Toyama Junji

  Department Of Circulation And Respiration The Research Institute Of Environmental Medicine Nagoya Un

• Fukutomi Tatsuya

  Department Of Cardiology Nagoya City University Medical School

• Fukutomi Tatsuya

  名古屋市立東市民病院 循環器内科

• Fukutomi Tatsuya

  名古屋市立大学 循環器内科

• Itoh Shigenori

  Toyohashi Heart Center

• Kodama Itsuo

  Department Of Circulation Research Institute Of Environmental Medicine Nagoya University

• Itoh Makoto

  First Department Of Internal Medicine Shiga University Of Medical Science

• Itoh Makoto

  Division Of Cardiovascular Medicine National Center For Geriatorics And Gerontology

• Suzuki S

  Department Of Cardiology Nagoya City University Medical School

• Okamoto Mitsuhiro

  Department of Cardiology, Aichi Prefectural Owari Hospital Cardiovascular Center

• Ito Shigenori

  First Department of Internal Medicine, Nagoya City University Medical School

• Fukutomi Tatsuya

  First Department of Internal Medicine, Nagoya City University Medical School

• Suzuki Shogo

  First Department of Internal Medicine, Nagoya City University Medical School

• Takamatsu J

  Division Of Transfusion Medicine Nagoya University Hospital

• Itou Makoto

  Department Of Internal Medicine And Bioregulation Nagoya City University Graduate School Of Medical

• Kodama Itsuo

  Department Of Cardiovascular Research R.i.e.m. Nagoya University

• Toyama Junji

  Department Of Cardiology Toyohashi Heart Center

• Suzuki Shogo

  Department Of Cardiovascular Medicine National Center For Geriatrics And Gerontology

• Fukutomi Tatsuya

  Department Of Cardiology Nagoya City University

• Itoh Shigenori

  Department Of Cardiology Toyohashi Heart Center

• Itou Makoto

  Division Of Cardiovascular Medicine National Center For Geriatorics And Gerontology

• Fukutomi Tatsuya

  First Department Of Internal Medicine Nagoya City University Medical School

• Toyama Junji

  Division Of Cardiology Aichi Prefectural Cardiovascular And Respiratory Center

• Toyama Junji

  Department Of Cardiology Aichi Prefectural Owari Hospital Cardiovascular Center

• Matsuda Tadashi

  The Department Of Urology Kansai Medical University

• Itoh Makoto

  First Department Of Internal Medicine Nagoya City University Medical School

• Fukutomi Tatsuya

  Department Of Internal Medicine And Pathophysiology Nagoya City University Graduate School Of Medica

• Suzuki Shogo

  First Department Of Internal Medicine Nagoya City University Medical School

• Suzuki Shogo

  Division Of Cardiology National Chubu Hospital

• Okamoto Mitsuhiro

  Department Of Cardiology Aichi Prefectural Owari Hospital Cardiovascular Center

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