Antiarrhythmic Properties of a Prior Oral Loading of Amiodarone in In Vivo Canine Coronary Ligation/Reperfusion-Induced Arrhythmia Model: Comparison With Other Class III Antiarrhythmic Drugs

Abstract

Abstract. Amiodarone, which is generally classified as class III antiarrhythmic drug in the Vaughan Williams classification, is widely used for the treatments of refractory arrhythmias. However, we previously reported that intravenous infusion of amiodarone (6.67 mg / kg per hour) did not suppress arrhythmias induced by coronary ligation / reperfusion in dogs. In this study, we examined effects of a prior oral loading of amiodarone on arrhythmias induced by coronary ligation / reperfusion. Sixteen female beagle dogs (8.5 -12.5 kg) were divided into two groups; one group was given amiodarone (40 mg / kg, orally, n = 8), and the other was given empty gelatin capsules (n = 8) 2 h before the operation. Dogs were anesthetized with pentobarbital and artificially ventilated. The left chest was opened, and the left anterior descending coronary artery was ligated for 30 min and then reperfused. The mean plasma concentration of amiodarone was over 1.3 mg / ml. Although the prior oral loading of amiodarone did not change the QT interval, amiodarone suppressed the number of ectopic beats during coronary ligation and the incidence of ventricular fibrillation during coronary ligation and reperfusion periods (P<0.05 vs control group). In conclusion, a prior oral loading of amiodarone suppressed arrhythmias induced by coronary ligation / reperfusion with a dose that did not prolong the QT interval. This antiarrhythmic property of amiodarone is different from those of the other class III drugs in that antiarrhythmic effects were accompanied by QT prolongation in our all previous studies.

Recycling the Purpose of Old Drugs to Treat Ovarian Cancer

“…In vitro experiments, using breast and prostate cancer cell lines, demonstrate that bisphosphonates promote apoptosis and block cell proliferation [ 139 , 140 ]. In addition, studies using OC cell lines and animal models have shown that bisphosphonates have an anti-proliferative and pro-apoptotic activity through the inhibition of cell proliferation and angiogenesis, induction of apoptosis, and activation of immune cells [ 141 , 142 , 143 , 144 , 145 , 146 ]. A recent study demonstrated that bisphosphonates inhibit OC cell lines proliferation in a concentration-dependent manner in vitro and potentiate a delay in tumour formation and a decrease in tumour cell proliferation in transgenic OC mouse models ( Figure 1 ) [ 147 ].…”

Arrhythmia Models for Drug Research: Classification of Antiarrhythmic Drugs

“…After stabilization following the surgical procedures, a drug was given by an intravenous bolus or by an infusion and then coronary occlusion followed by reperfusion was performed. In some experiments, chronic oral administration of drugs for days or weeks before the experiment was performed (87,88). The occurrence of PVC or VF was monitored by continuous ECG recordings.…”

“…As stated above, some K + -channel blockers were effective, but others, amiodarone (50,87), dofetilide (48), KCB-328 (49), sematilide (47) and, d-sotalol (84), were not effective in halothane-anesthetized dogs; and dofetilide (48) and sematilide (47) were not effective in pentobarbital-anesthetized dogs (6). Also in the halothane anesthetized low heart rate open chest dogs, some of the K + -channel blockers, amiodarone (50), dofetilide (48), E-4031 (46), KCB-328 (49), nifekalant (84), and sematilide (47), showed a proarrhythmic effect by spontaneously inducing PVC and VT before applying coronary occlusion, but these arrhythmias before applying coronary occlusion were not observed in high heart rate pentobarbital-anesthetized dogs by dofetilide (48) (88), administration in rat models.…”

Report and Recommendations of the Workshop of the European Centre for the Validation of Alternative Methods for Drug-Induced Cardiotoxicity

“…Additionally, depending on their respective binding/unbinding time constants, drugs may or may not interact with the conduction velocity and modify the duration of the repolarization phase differently (e.g. class IA, class IB, class IC in the Vaughan-Williams classification) [41,42]. Thus, a compound which unbinds from the channel with a long time constant (e.g.…”