Ghasi Samuel, Onuaguluchi Gilbert
Department of Pharmacology and Therapeutics, College of Medicine, University of Nigeria, Enugu, Nigeria.
Am J Ther. 2007 Nov-Dec;14(6):524-32. doi: 10.1097/01.pap.0000249959.74771.a1.
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.
在麻醉的Wistar大鼠中测定了4种不同剂量（15、30、60和100mg/kg）枸橼酸哌嗪引起的急性心电图（ECG）变化。心率出现剂量依赖性降低，从15mg/kg剂量时的9.03%±2.97%降至100mg/kg体重时的30.84%±3.4%。P-R间期相对于平衡值呈剂量依赖性增加，从15mg/kg时的10.69%±2.82%增加至100mg/kg时的24.79%±2.71%。同样，经心率校正的Q-T间期（Q-Tc）也呈剂量依赖性增加，从15mg/kg时的4.7%±1.89%增加至100mg/kg时的29.40%±6.09%。与对照组的值相比，除了15mg/kg剂量组外，所有这些变化均具有统计学意义（P<0.05）。除了100mg/kg剂量外，哌嗪对QRS波群时限没有任何影响，在该剂量下，7只大鼠中有3只出现明显增宽。3只大鼠还出现了心律失常现象，包括各种形式的房室（AV）阻滞，有时伴有室性自主心律。还观察到由于窦房结抑制和房室阻滞导致的严重心动过缓。在此浓度（100mg/kg）下，7只大鼠中有3只在给药后30分钟内死于完全性心脏阻滞。得出的结论是，建议的抗心律失常剂量（静脉注射时为15mg/kg）甚至四倍于此剂量的枸橼酸哌嗪均未出现提示心脏毒性的心电图异常。然而，在100mg/kg时可能会出现非常严重的心电图异常，伴有严重心脏阻滞和死亡。
