Animal models for studying arrhythmogenic drug actions

• Project/Area Number: 04454541
• Research Category: Grant-in-Aid for General Scientific Research (B)
• Allocation Type: Single-year Grants
• Research Field: 応用薬理学・医療系薬学
• Research Institution: Yamanashi Medical College
• Principal Investigator: HASHIMOTO Keitaro Yamanashi Med Col Dept Pharmacol Professor, 医学部, 教授 (10004665)
• Co-Investigator(Kenkyū-buntansha): MOTOMURA Shigeru Yamanashi Med Col Dept Pharmacol Associate Professor, 医学部, 助教授 (40091756)
• Project Period (FY): 1992 – 1993
• Project Status: Completed (Fiscal Year 1993)
• Budget Amount: ¥6,300,000 (Direct Cost: ¥6,300,000); Fiscal Year 1993: ¥1,200,000 (Direct Cost: ¥1,200,000); Fiscal Year 1992: ¥5,100,000 (Direct Cost: ¥5,100,000)
• Keywords: arrhythmogenic action / class III antiarrhythmic drugs / class I antiarrhythmic drugs / positive inotropic drugs / 24 hr ambulatory ECG monitoring system / 抗不整脈薬 / 長時間心電計

Research Abstract

To examine potential arrhythmogenic side effects of cardiac drugs, especially those of antiarrhythmic drugs and positive inotropic drugs, two types of dog experiments were performed. Using the 24 hr ECG monitoring, long term recording of dogs given oral class III antiarrhythmic drugs, MS-551 and sematilide, both induced in about 30% of dogs premature ventricular contractions, but did not induce torsade de pointes like severe ventricular tachycardia (VT). Also using canine VT models, induced by either coronary ligation, digitalis toxication or halothane adrenaline combination, new positive inotropic drugs, OPC-18790 and NKH477, aggravated halothane adrenaline VT, but could be used with digitalis and under myocardial ischemic condition. Long term arrhythmogenic properties of drugs could not be examined using the present methods and new animal models may be needed for this purpose.

Research Products

• [Publications] Z.Wu,K.Hashimoto et al.: "Effects of OPC-18790,a new positive inotropic agent,on canine ventricular arrhythmias." Japan.J.Pharmacol.63. 399-404 (1993)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] A.Hirasawa,K.Hashimoto et al.: "Effects of a new forskolin derivatives,NKH477,on canine ventricular arrhythmia models." J.Cardiovasc.Pharmacol.22. 847-851 (1993)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Wu, Z., Awaji, T., Abe, H., Motomura, S.and Hashimoto, K.: "Effects of OPC-18790, a new positive inotropic agent, on canine ventricular arrhythmias." Jap. J.Pharmacol.63. 399-404 (1993)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Hirasawa, A., Awaji, T., Hosono, M., Haruno, A.and Hashimoto, K.: "Effects of a new forskolin derivatives, NKH477, on canine ventricular arrhythmia models." J.Cardiovasc. Pharmacol.22. 847-851 (1993)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Z.Wu,K.Hashimoto et al.: "Effects of OPC-18790,a new positive inotropic agent,on canine ventricular arrhythmias." Japan.J.Pharmacol. 63. 399-404 (1993)
• [Publications] A.Hirasawa,K.Hashimoto et al.: "Effects of a new forskolin derivatives,NIK477,on canine ventricular arrhythmia models" J.Cardiovasc.Pharmacol.22. 847-851 (1993)
• [Publications] Keitaro Hashimoto: "Arrhythmias associated with myocardial ischemia and their modulation by antiarrhythmic drugs" 循環制御. 13. 373-383 (1992)
• [Publications] Akira Hirasawa Akihiko Haruno Takushi Matsuzaki Keitaro Hashimoto: "Effects of a new antiarrhythmic drug, SD-3212, on canine ventricular arrhythmia models" Japanese Heart Journal. 33. 851-861 (1992)