Department of Cardiothoracic Surgery, Cardiovascular Research Institute Maastricht, 6200 MD Maastricht, the Netherlands.
J Cardiovasc Pharmacol. 2009 Oct;54(4):355-63. doi: 10.1097/FJC.0b013e3181bad042.
Amiodarone and sotalol are frequently used in the treatment of atrial fibrillation. However, oral and intravenous (IV) therapy with these drugs has suboptimal efficacy and is associated with serious extracardiac side effects. We hypothesized that intrapericardial (IPC) delivery produces antiarrhythmic effects at lower plasma drug concentrations than IV delivery. Goats (n = 27) were randomised into 5 groups receiving either IPC vehicle, amiodarone (IV or IPC) or dl-sotalol (IV or IPC). Epicardial and endocardial atrial effective refractory period and atrial response to burst pacing (rapid atrial response, RAR) were assessed before and after 3 hours of drug infusion at 2 mg.kg.h. IPC delivery produced steeply decreasing drug concentrations from epicardium to endocardium in both atria and ventricles. Plasma drug concentrations were significantly lower in IPC than in IV groups. IPC amiodarone and sotalol reduced epicardial RAR inducibility (-74% +/- 20% and -66% +/- 30%, respectively) compared with IV delivery (-11% +/- 17% and -17% +/- 28%, respectively; P < 0.05). Endocardial RAR inducibility was only reduced in the IPC amiodarone group (-70% +/- 17%, P < 0.05). In conclusion, IPC delivery of amiodarone and sotalol increases atrial drug concentration and antiarrhythmic effects at reduced plasma drug concentrations. These potential benefits are particularly prominent for IPC delivered amiodarone.
胺碘酮和索他洛尔常用于治疗心房颤动。然而，这些药物的口服和静脉（IV）治疗效果并不理想，且伴有严重的心脏外副作用。我们假设心包内（IPC）给药比静脉内（IV）给药产生抗心律失常作用所需的药物血浆浓度更低。将 27 只山羊随机分为 5 组，分别接受心包内载体、胺碘酮（IV 或 IPC）或 dl-索他洛尔（IV 或 IPC）。在 2mg·kg·h 的药物输注 3 小时前后，评估心外膜和心内膜心房有效不应期和心房对爆发性起搏的反应（快速心房反应，RAR）。IPC 给药在心房和心室的心外膜和心内膜均产生药物浓度从心外膜到心内膜逐渐降低的现象。IPC 组的血浆药物浓度明显低于 IV 组。与 IV 给药组相比，IPC 胺碘酮和索他洛尔降低了心外膜 RAR 的诱导性（分别为-74%±20%和-66%±30%）（分别为-11%±17%和-17%±28%；P<0.05）。只有 IPC 胺碘酮组的心内膜 RAR 诱导性降低（-70%±17%；P<0.05）。总之，IPC 给药可增加心房药物浓度，并在降低血浆药物浓度的情况下提高抗心律失常作用。这些潜在的益处，特别是对于 IPC 给药的胺碘酮，更为显著。
