2002 Fiscal Year Final Research Report Summary

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

Research Project

Project/Area Number	13670081
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	General pharmacology
Research Institution	University 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
Keywords	Na / H exchange / Na / 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.

Research Products

(46 results)

All Other

All Publications (46 results)

[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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
[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

2002 Fiscal Year Final Research Report Summary

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

Principal Investigator

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

Research Products

[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

[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

[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

[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

[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

[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

[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

[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

[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

[Publications] Takahara A. et al.: "AH-1058 : A novel cardioselective Ca2+ channel blocker"Cardiovasc. Drugs. Rev.. 19. 279-296 (2001)

Description

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

Description

[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

[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

[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

[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

[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

[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

[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

[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

[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

[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

[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

[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

[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

[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

[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

[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

[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

[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

[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

[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

[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

[Publications] Noguchi K., et al.: "Effects of HNS-32, a novel antiarrhythmic agent, on gunea-pig myocardium"Pharmacology. 64. 36-42 (2002)

Description

[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

[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

[Publications] Takahara A., et al.: "AH-1058: A novel cardioselective Ca^<2+> channel blocker"Cardiovasc. Drugs Rev.. 19. 279-296 (2001)

Description

[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

[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)