Time course of effect of piperazine citrate on the electrocardiogram of the rat.
The acute electrocardiographic (ECG) changes induced by 4 different doses of piperazine citrate (15, 30, 60, and 100 mg/kg) were determined in the anesthetized Wistar rat. A dose-dependent reduction in heart rate occurred, from 9.03%+/-2.97% at a dose of 15 mg/kg to 30.84%+/-3.4% at 100 mg/kg body weight. The P-R interval showed dose-dependent increases over values at equilibration, increasing from 10.69% +/-2.82% at 15 mg/kg to 24.79%+/-2.71% at 100 mg/kg. Similarly, the Q-T interval corrected for heart rate (Q-Tc) showed dose-dependent increases, from 4.7%+/-1.89% at 15 mg/kg to 29.40%+/-6.09% at 100 mg/kg. In comparison with values for controls, all these changes except those associated with 15 mg/kg were statistically significant (P<0.05). Piperazine did not have any effect on the duration of the QRS complex except at 100 mg/kg, the dose at which marked widening occurred in 3 of the 7 rats. Dysrhythmic phenomena, including various forms of atrioventricular (AV) block, sometimes with idioventricular rhythms, were also evident in the 3 rats. Severe bradycardia from sino-atrial depression and AV block was also observed. At this concentration (100 mg/kg), 3 of 7 rats died of complete heart block within 30 minutes of drug administration. It was concluded that piperazine citrate at the suggested antiarrhythmic dose (15 mg/kg intravenously) and even at four times that dose was associated with no ECG abnormality suggestive of cardiotoxicity. However, at 100 mg/kg very serious ECG aberrations can occur, with severe heart block and death.
Ghasi
Samuel
S
Department of Pharmacology and Therapeutics, College of Medicine, University of Nigeria, Enugu, Nigeria. samuelghasi@yahoo.com
Onuaguluchi
Gilbert
G
D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000871:Anthelmintics; D010879:Piperazines; C006589:piperazine citrate