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Effects of Na/H and Na/Ca exchange inhibitors on ischemia/reperfusion arrhythmias

Research Project

Project/Area Number13670081
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionUniversity of Yamanashi Faculty of Medicine

Principal Investigator

HASHIMOTO Keitaro  University of Yamanashi Faculty of Medicine, Professor, 医学部, 教授 (10004665)

Co-Investigator(Kenkyū-buntansha) KOMORI Sadayoshi  Nirasaki Shimin Hospital, Vise director, 副院長 (30162069)
Project Period (FY) 2001 – 2002
Project Status Completed(Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost : ¥3,600,000)
Fiscal Year 2002 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 2001 : ¥2,700,000 (Direct Cost : ¥2,700,000)
KeywordsNa / H exchange / Ca exchange / arrhythmia / ischemia / sudden cardiac death / arrhythmia model
Research Abstract

Na/H exchange inhibitors have been shown by us and by others to suppress ischemia/reperfusion arrhythmias in rats and dogs, to improve hemodynamic recovery and to decrease infarct size. We confirmed again the effectiveness of Na/H exchange inhibition using a new drug, FR168888. This protective effect also involve Na/Ca exchange inhibition, but a new Na/Ca exchange inhibitor, SEA0300, did not show protection against ischemia/reperfusion arrhythmias. Since SEA0300 suppressed digitalis arrhythmias, which is thought to be due to Ca overload, further investigation is necessary to clarify in vivo mechanism of action of SEA0300.

Report

(3results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report

Research Products

(61results)

All Other

All Publications

  • [Publications] Takahara A. et al.: "Cardiovascular action of a cardioselective Ca^<2+> channel blocker AH-1058 in conscious dogs assessed by telemetry"Euro. J. Pharmacol.. 413. 101-108 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tanaka Y. et al.: "HNS-32 a novel azulene-1-carboxamidine derivative, inhibits nifedipine-sensitive and-insensitive contraction of the isolted rabbit aorta"Naunyn-Schmiedebergs Archi. Pharmacol.. 363. 344-352 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahara A. et al.: "Utilization of telemetry system to assess the cardiovascular profile of AH-1058, a new cardioselective Ca^<2+> channel blocker, in conscious dogs"Jpn. J. Pharmacol.. 85. 331-334 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Homma, N. et al.: "Electrophysiologic effects of an antiarrhythmic agent, bidisomide, on sodium current in isolated rat ventricular myocytes : Comparison with mexiletine and disopyramide"Jpn. J. Pharmacol.. 86. 23-31 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyamoto, S. et al.: "Slowing Na^+ channel inactivation prolongs QT interval and aggravates adrenaline-induced arrhythmias"Jpn. J. Pharmacol.. 86. 114-119 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugiyama, A. et al.: "In vivo canine model comparison of cardiohemodynamic and electrophysiological effects of a new antipsychotic drug aripiprazole (OPC-14597) to haloperidol"Toxicol. Appl. Pharmacol.. 173. 120-128 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahara A. et al.: "In vivo antiarrhythmic profile of AP-792 assessed in different canine arrhythmia models"Jpn. J. Pharmacol.. 87. 21-26 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugiyama A. et al.: "Acute electropharmacological effects of intravenously administered amiodarone assessed in the in vivo canine model"Jpn. J. Pharmacol.. 87. 74-82 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugiyama A. et al.: "Cardiac electrophysiological and hemodynamic effects of sildenafil, a PDE5 inhibitor, in anesthetized dogs"J. Cardiovasc. Pharmacol.. 38. 940-946 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahara A. et al.: "AH-1058 : A novel cardioselective Ca2+ channel blocker"Cardiovasc. Drugs. Rev.. 19. 279-296 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Noguchi K et al.: "Effects of HNS-32, a novel antiarrhythmic agent, on guinea-pig myocardium"Pharmacology. 64. 36-42 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zhu B-M et al.: "Inhibitory effects of pre-ischemic and post-ischemic treatment with FR 168888, a new Na+/H+ eschange inhibitor, on reperfusion-induced ventricular arrhythmias in anesthetized rat"Jpn. J. Pharmacol.. 88. 93-99 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugiyama A et al.: "Electrophysiological, anatomical and histological remodeling of the heart to AV block enhances susceptibility to arrhythmogenic effects of QT-prolonging drugs"Jpn. J. Pharmacol.. 88. 341-350 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugiyama A et al.: "Effects of a typical I_<kr> channel blocker sematilide on the relationship between ventricular repolarization, refractoriness and onset of torsades de pointes"Jpn. J. Pharmacol.. 88. 414-421 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saitoh M. et al.: "Cardiovascular effects of orally administered HNS-32, an originally synthesized azulene-1-carboxamidine derivative, assessed in the in vivo rat model"Jpn. J. Pharmacol.. 89. 316-319 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida H. et al.: "Comparison of the in vivo electrophysiological and proarrhythmic effects of amiodarone with those of a selective class III drug, sematilide, using a canince chronic atrioventricular block model"Circulation J.. 66. 758-762 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Horii I. et al.: "Evelopment of telemetry system in the common marmoset. Cardiovascular effects of astemizole and nicardipine"J. Toxicological Sciences. 27. 123-130 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida H. et al.: "Effects of disopyramide and mexiletine on the terminal repolarization process of the in situ heart assessed using the halothane-anesthetized in vivo canine model"Circulation J.. 66. 857-862 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyamoto S et al.: "KB-R7943, a Na^+/Ca^<2+> exchange inhibitor, does not suppress ischemia-reperfusion arrhythmias nor digitalis arrhythmias in dogs"Jpn. J. Pharmacol.. 90. 229-235 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoneyama M. et al.: "Cardiovascular and adenylate cyclase stimulating effects of colforsin daropate, a water-soluble forskolin derivative, compared with those of isoproterenol, dopamine and dobutamine"Circulation J.. 66. 1150-1154 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zhu B-M et al.: "Does Cl-/HCO_3-exchange play an important role in reperfusion arrhythmias in rats?"Europ. J. Pharmacol.. 460. 43-50 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugiyama A. et al.: "Femotidine does not induce long QT syndrome : experimental evidence from in vitro and in vivo test sytems"Europ. J. Pharmacol.. 466. 137-146 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hashimoto K. et al.: "Na/H exchange and arrhythmia. "Myocardial Ischemia and Preconditioning""Edited by Naranjan S.Dhalla, Nobuaki Takeda, Manjeet Singh, Anton Lukas. Kluwer Academic Publishers, Boston. 389-397 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahara A., et al.: "Cardiovascular action of a cardioselective Ca^<2+> channel blocker AH-1058 in conscious dogs assessed by telemetry"Euro. J. Pharmacol.. 413. 101-108 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tanaka Y., et al.: "HNS-32 a novel azulene-1-carboxamidine derivative, inhibits nifedipine-sensitive and -insensitive contraction of the isolated rabbit aorta"Naunyn-Schmiedebergs Archi. Pharmacol.. 363(3). 344-352 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahara A., et al.: "Utilization of telemetry system to assess the cardiovascular profile of AH-1058, a new cardioselective Ca^<2+> channel blocker, in conscious dogs"Jpn. J. Pharmacol.. 85. 331-334 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Homma, H., et al.: "Electrophysiologic effects of an antiarrhythmic agent, bidisomide, on sodium current in isolated rat ventricular myocytes: Comparison with mexiletine and disopyramide"Jpn. J. Pharmacol.. 86. 23-31 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyamoto, S., et al.: "Slowing Na^+ channel inactivation prolongs QT interval and aggravates adrenaline-induced arrhythmias"Jpn. J. Pharmacol.. 86. 114-119 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugiyama, A., et al.: "In vivo canine model comparison of cardiohemodynamic and electrophysiological effects of a new antipsychotic drug aripiprazole (OPC-14597) to haloperidol"Toxicol. Appl. Pharmacol.. 173. 120-128 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahara A., et al.: "In vivo antiarrhythmic profile of AP-792 assessed in different canine arrhythmia models"Jpn. J. Pharmacol.. 87. 21-26 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugiyama A., et al.: "Acute electropharmacological effects of intravenously administered amiodarone assessed in the in vivo canine model"Jpn. J. Pharmacol.. 87. 74-82 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugiyama A., et al.: "Cardiac electrophysiological and hemodynamic effects of sildenafil, a PDES inhibitor, in anesthetized dogs"J. Cardiovasc. Pharmacol.. 38. 940-946 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Noguchi K., et al.: "Effects of HNS-32, a novel antiarrhythmic agent, on gunea-pig myocardium"Pharmacology. 64. 36-42 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zhu B-M, et al.: "Inhibitory effects of pre-ischemic and post-ischemic treatment with FR 168888, a new Na^+/H^+ exchange inhibitor, on reperfusion-induced ventricular arrhythmias in anesthetized rat"Jpn. J. Pharmacol.. 88. 93-99 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugiyama A., et al.: "Electrophysiological, anatomical and histological remodeling of the heart to AV block enhances susceptibility to arrhythmogenic effects of QT-prolonging drugs"Jpn. J. Pharmacol.. 88. 341-350 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahara A., et al.: "AH-1058: A novel cardioselective Ca^<2+> channel blocker"Cardiovasc. Drugs Rev.. 19. 279-296 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugiyama A, and Hashimoto K.: "Effects of a typical I_<kr> channel blocker sematilide on the relationship between ventricular repolarization, refractoriness and onset of torsades de pointes"Jpn. J. Pharmacol.. 88. 414-421 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saitoh M, et al.: "Cardiovascular effects of orally administered HNS-32, an originally synthesized azulene-1-carboxamidine derivative, assessed in the in vivo rat model"Jpn. J. Pharmacol.. 89. 316-319 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida H, et al.: "Comparison of the in vivo electrophysiological and proarrhythmic effects of amiodarone with those of a selective class III drug, sematilide, using a canine chronic atrioventricular block model"Circulation J.. 66 (8). 758-762 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Horii I, et al.: "Evelopment of telemetry system in the common marmoset. Cardiovascular effects of astemizole and nicardipine"J. Toxicological Sciences. 27 (2). 123-130 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida H, et al.: "Effects of disopyramide and mexiletine on the terminal repolarization process of the in situ heart assessed using the halothane-anesthetized in vivo canine model"Circulation J.. 66(9). 857-862 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyamoto S, et al.: "KB-R7943, a Na^+・Ca^<2+> exchange inhibitor, does not suppress ischemia・reperfusion arrhythmias nor digitalis arrhythmias in dogs"Jpn. J. Pharmacol.. 90. 229-235 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoneyama M, et al.: "Cardiovascular and adenylate cyclase stimulating effects of colforsin daropate, a water-soluble forskolin derivative, compared with those of isoproterenol, dopamine and dobutamine"Circulation J.. 66(12). 1150-1154 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zhu B-M, et al.: "Does Cl^-/HCO^<3-> exchange play an important role in reperfusion arrhythmias in rats?"Europ. J. Pharmacol.. 460. 43-50 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugiyama A, et al.: "Femotidine does not induce long QT syndrome: experimental evidence from in vitro and in vivo test systems"Europ. J. Pharmacol.. 466. 137-146 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hashimoto K, et al. edited by Naranjan S.Dhalla, Nobuaki Takeda, Manjeet Singh, Anton Lukas: "Na/H exchange and arrhythmia in: Myocardial Ischemia and Preconditioning"Kluwer Academic Publishers. 389-397 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Noguchi K: "Effects of HNS-32, a novel antiarrhythmic agent, on guinea-pig myocardium"Pharmacology. 64. 36-42 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Zhu B-M: "Inhibitory effects of pre-ischemic and post-ischemic treatment with FR 168888, a new Na+/H+ eschange inhibitor, on reperfusion-induced ventricular arrhythmias in anesthetized rat"Jpn.J.Pharmacol.. 88. 93-99 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sugiyama A: "Electrophysiological, anatomical and histological remodeling of the heart to AV bock enhances susceptibility to arrhythmogenic effects of QT-prolonging drugs"Jpn.J.Pharmacol.. 88. 341-350 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sugiyama A: "Effects of a typical I_<Kr> channel blocker sematilide on the relationship between ventricular repolarization, refractoriness and onset of torsades de pointes"Jpn.J.Pharmacol.. 88. 414-41 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Miyamoto S: "KB-R7943, a Na^+/Ca^<2+> exchange inhibitor, does not suppress ischemia reperfusion arrhythmias nor digitalis arrhythmias in dogs"Jpn.J.Pharmacol.. 90. 229-235 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Zhu B-M: "Does Cl-/HCO_3-exchange play an important role in reperfusion arrhythnias in rats?"Europ.J.Pharmacol.. 460. 43-50 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takahara A. et al.: "Cardiovascular action of a cardioselective Ca^<2+> channel blocker AH-1058 in conscious dogs assessed by telemetry"Euro. J. Pharmacol. 413. 101-108 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takahara A. et al.: "Utilization of telemetry system to assess the cardoiovascular profile of AH-1058, a new cardioselective Ca^<2+> channel blocker, in conscious dogs"Jpn. J. Pharmacol. 85. 331-334 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Homma N, et al.: "Electrophysiologic effects of an antiarrhythmic agent, bidisomide, on sodium current in isolated rat ventricular myocytes : Comparison with mexiletime and disopyramide"Jpn. J. Pharmacol. 86. 23-31 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Miyamoto S, et al.: "Slowing Na^+ channel inactivation prolongs QT interval and aggravates adrenaline-induced arrhythmias"Jpn. J. Pharmacol. 86. 114-119 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sugiyama A. et al.: "Electropharmacologic effects of a new phosphodiesterase III inhibitor, toborinone(OPC-18790), assessed in an in vivo canine model"J. Cardiovasc. Pharmacol. 38. 268-277 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takahara A. et al.: "In vivo antiarrhythmic profile of AP-792 assessed in different canine arrhythmia models"Jpn. J. Pharmacol. 87. 21-26 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sugiyama A. et al.: "Acute electropharmacological effects of intravenously administered amiodarone assessed in the in vivo canine model"Jpn. J. Pharmacol. 87. 74-82 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Noguchi K, et al.: "Effects of HNS-32, a novel antiarrhythmic agent, on guinea-pig myocardium"Pharmacology. 64. 36-42 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Zhu BM et al.: "Inhibitory effects of pre-ischemic and post-ischemic treatment with FR 168888, a new Na^+/H^+ eschange inhibitor, on reperfusion-induced ventricular arrhythmias in anesthetized rat"Jpn. J. Pharmacol. 88. 93-99 (2002)

    • Related Report
      2001 Annual Research Report

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Published : 2001-04-01   Modified : 2016-04-21  

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