Characteristics of electrocardiographic changes with some representative antiarrhythmic drugs in adult rats.
The characteristics of ECG changes with representative antiarrhythmic drugs; procainamide (PA) (class Ia), lidocaine (LC) (class Ib), propranolol (PN) (class II), and verapamil (VP) (class IV) were investigated in adult rats. Action potential (AP) was also recorded from myocardial cells during electrical stimuli with frequencies of 1-5 Hz. All the four drugs produced ECG abnormalities which contained AV and SA blocks at middle and high dose levels. Three drugs except VP induced a prolongation of QRS complex and notched QRS at low or middle dose level. As compared such effects with those in dogs and humans, some differences were noted as follows: (1) a dose-dependent prolongation of QT interval by LC and PN, and (2) a shortening of RR interval by VP at the dose of 0.6 mg/kg or less. LC and PN elongated the QT interval in the unipolar precordial chest lead ECGs at right anterior chest positions. These two drugs did not affect the duration of AP (APD90), whereas maximum upstroke velocity (Vmax) decreased. These results suggest that the prolongation of QT interval with LC and PN was due to a delay in local ventricular conduction time, especially on the right ventricle. The shortening of RR interval by VP was clearly blocked by the pretreatment with PN, indicating that this shortening reflected the sympathetic nervous reflex presumably due to the peripheral vasodilation effect of VP.
Suzuki
J
J
Development Research Laboratories, Banyu Pharmaceutical Co., Ltd., Saitama, Japan.
Tsubone
H
H
Sugano
S
S
D000200:Action Potentials; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects / Q000662:veterinary*; D006321:Heart / Q000187:drug effects*; D008012:Lidocaine / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D011342:Procainamide / Q000493:pharmacokinetics / Q000494:pharmacology; D011433:Propranolol / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains / Q000502:physiology*; D014700:Verapamil / Q000493:pharmacokinetics / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D008012:Lidocaine; D011433:Propranolol; D014700:Verapamil; D011342:Procainamide