2000 Fiscal Year Annual Research Report

Na/H交換抑制薬の虚血性不整脈抑制機序

Research Project

Project/Area Number	11670085
Research Institution	Yamanashi Medical University
Principal Investigator	橋本敬太朗山梨医科大学, 医学部, 教授 (10004665)
Co-Investigator(Kenkyū-buntansha)	中山貢一静岡県立大学, 薬学部, 教授 (50112769) 小森貞嘉山梨医科大学, 医学部, 教授 (30162069)
Keywords	Na / H交換 / 不整脈 / 虚血 / 動物モデル
Research Abstract	新しい選択的なNa/H交換機構の阻害薬として、本年度はSMP-300とFR168888が従来の阻害薬と同様に丸ごとの動物での抗不整脈作用があるかを検討した。橋本と小森はFR168888(0.3-10mg/kg)が、ラットにおいて、虚血後に投与しても、また再潅流と同時に投与しても有効であることを示し、さらに虚血中に低下する血圧を上昇させる従来のNa/H交換阻害薬になかった良い作用も認められた。今後イヌでの作用を検討する予定である。またSMP-300は中山がイヌを用いて検討したが,1mg/kgの投与で30分の左冠動脈前下行枝の虚血による不整脈と再潅流心室細動を抑制した。さらにカルシウム心筋内過負荷が虚血再潅流とは異なるが、カルシウムチャネルを開いて起こすことが発生機序と考えられるイヌのアドレナリン不整脈にも弱いながら有効であった。Na/H交換阻害薬は共通して、虚血に伴うカルシウム心筋内過負荷で発生するイヌやラットの虚血再潅流不整脈を特に抑制することが示されたので、今後は臨床に於いても虚血障害や再潅流障害を経皮的冠動脈形成術や血栓溶解術時に併用することにより、心筋壊死巣の縮小や不整脈などの予防を証明する実験の基礎資料を提供したことになすと考えている。

Research Products
(9 results)

All Other

All Publications (9 results)

[Publications] Naito H.: "Effects of zatebradine and propranolol on canine ischemia and reperfusion-induced arrhythmias."Europ.J.Pharmacol.. 388・2. 171-176 (2000)
[Publications] Saitoh M.: "Effects of HNS-32,a novel antiarrhythmic durg,on ventricular arrhythmias induced by coronary artery occlusion and rcperfusion in anesthetized rats."Molecular and Cellular Biochemistry. 205・1-2. 133-140 (2000)
[Publications] Homma N.: "Both α_<1A>-and α_<1B>-adrenergic receptor subtypes couple to the transient outward current (I_<To>) in rat ventricular myocytes."Brit.J.Pharmacol.. 129. 1113-1120 (2000)
[Publications] Miyamoto S.: "QT-prolonging class I drug,disopyramide,does not aggravate but suppresses adrenaline-induced arrhythmias.Comparison with cibenzoline and pilsicainide."Europ.J.Pharmacol.. 400. 263-269 (2000)
[Publications] Akie Y.: "Proarrhythmic effects of four class III antiarrhythmic drugs,MS-551,sematilide,dofetilide and KCB328,examined using ambulatory ECG."Asia Pacific J.Pharmacol.. 14. 101-109 (2000)
[Publications] Takusagawa M.: "The inhibitory effects of carvedilol against arrhythmias induced by coronary reperfusion in anesthetized rats."Cardiovasc Pharmacol Therapeut. 5・2. 105-112 (2000)
[Publications] Matsumura K.: "Protein kinase C is involved in cardioprotective effects of ischemic preconditioning on infarct size and ventricular arrhythmia in rats in vivo."Cell.Biochem.. 214. 39-45 (2000)
[Publications] Chino D.: "Specific augmentation of plantar skin blood flow by lipo-PGE1 assessed in tetrodotoxin-and N(G)-nitro-L-arginine-treated rats."J.Cardiovasc.Pharmacol.. 35. 630-637 (2000)
[Publications] Obara K.: "Protein kinase C delta but not PKC epsilon activity is involved in contractile potentiation by endothelin-1 in the porcine coronary artery."J.Cardiovasc.Pharmacol.. 36. S120-S121 (2000)

2000 Fiscal Year Annual Research Report

Na/H交換抑制薬の虚血性不整脈抑制機序

Principal Investigator

橋本 敬太朗 山梨医科大学, 医学部, 教授 (10004665)

Research Products

[Publications] Naito H.: "Effects of zatebradine and propranolol on canine ischemia and reperfusion-induced arrhythmias."Europ.J.Pharmacol.. 388・2. 171-176 (2000)

[Publications] Saitoh M.: "Effects of HNS-32,a novel antiarrhythmic durg,on ventricular arrhythmias induced by coronary artery occlusion and rcperfusion in anesthetized rats."Molecular and Cellular Biochemistry. 205・1-2. 133-140 (2000)

[Publications] Homma N.: "Both α_<1A>-and α_<1B>-adrenergic receptor subtypes couple to the transient outward current (I_<To>) in rat ventricular myocytes."Brit.J.Pharmacol.. 129. 1113-1120 (2000)

[Publications] Miyamoto S.: "QT-prolonging class I drug,disopyramide,does not aggravate but suppresses adrenaline-induced arrhythmias.Comparison with cibenzoline and pilsicainide."Europ.J.Pharmacol.. 400. 263-269 (2000)

[Publications] Akie Y.: "Proarrhythmic effects of four class III antiarrhythmic drugs,MS-551,sematilide,dofetilide and KCB328,examined using ambulatory ECG."Asia Pacific J.Pharmacol.. 14. 101-109 (2000)

[Publications] Takusagawa M.: "The inhibitory effects of carvedilol against arrhythmias induced by coronary reperfusion in anesthetized rats."Cardiovasc Pharmacol Therapeut. 5・2. 105-112 (2000)

[Publications] Matsumura K.: "Protein kinase C is involved in cardioprotective effects of ischemic preconditioning on infarct size and ventricular arrhythmia in rats in vivo."Cell.Biochem.. 214. 39-45 (2000)

[Publications] Chino D.: "Specific augmentation of plantar skin blood flow by lipo-PGE1 assessed in tetrodotoxin-and N(G)-nitro-L-arginine-treated rats."J.Cardiovasc.Pharmacol.. 35. 630-637 (2000)

[Publications] Obara K.: "Protein kinase C delta but not PKC epsilon activity is involved in contractile potentiation by endothelin-1 in the porcine coronary artery."J.Cardiovasc.Pharmacol.. 36. S120-S121 (2000)

橋本敬太朗山梨医科大学, 医学部, 教授 (10004665)