Sintov A, Scott W A, Gallagher K P, Levy R J
Department of Pediatrics, C. S. Mott Children's Hospital, University of Michigan Medical School, Ann Arbor 48109.
Pharm Res. 1990 Jan;7(1):28-33. doi: 10.1023/a:1015875223446.
Epicardial antiarrhythmic drug administration was studied as a therapeutic approach for experimental ventricular tachycardia (VT) in an open-chest dog model. Lidocaine-polyurethane matrices (28%, w/w) were formulated as a model system. Matrices were placed on the left ventricular epicardium in each of 23 anesthetized open-chest dogs with ouabain-induced VT, to evaluate effectiveness in restoring sinus rhythm. Conversion occurred in all animals treated with matrices containing 300 mg or more of lidocaine after 1.5 to 7.0 min. The matrix lidocaine content correlated linearly with the time required for conversion to sinus rhythm (r = 0.75, P = 0.0002); irrespective of matrix size the myocardial/plasma lidocaine ratio was 20.1 +/- 4.2 (mean +/- SD) at the time of conversion. In a separate series of five dogs without ventricular tachycardia, systolic wall thickening measured with sonomicrometers after 5 min of controlled-release lidocaine administration (500- to 1000-mg matrix lidocaine content, 7.48 +/- 3.49-mg/kg dose) was only minimally diminished (-14.1%) and this effect was observed only at the site of matrix placement on the anterior-apical epicardium. In contrast, intracoronary injection of 0.3 or 1.0 mg/kg of lidocaine-HCl resulted in complete elimination of wall thickening or replacement by systolic thinning. Thus epicardial administration of lidocaine from polyurethane matrices was an effective means of treating ouabain-induced ventricular tachycardia. Regional myocardial function in the vicinity of the matrices was modified to a very limited degree, supporting the view that the matrices can be used safely, without serious risk to ventricular contractile performance.
在开胸犬模型中，研究了心外膜抗心律失常药物给药作为实验性室性心动过速（VT）的一种治疗方法。配制了利多卡因-聚氨酯基质（28%，w/w）作为模型系统。将基质放置在23只接受哇巴因诱导的VT的麻醉开胸犬的每只左心室心外膜上，以评估恢复窦性心律的有效性。在用含有300mg或更多利多卡因的基质治疗的所有动物中，在1.5至7.0分钟后发生了心律转换。基质利多卡因含量与转换为窦性心律所需的时间呈线性相关（r = 0.75，P = 0.0002）；无论基质大小如何，转换时心肌/血浆利多卡因比值为20.1±4.2（平均值±标准差）。在另一组五只没有室性心动过速的犬中，在给予控释利多卡因5分钟后（基质利多卡因含量为500至1000mg，剂量为7.48±3.49mg/kg），用超声微测仪测量的收缩期壁增厚仅略有减少（-14.1%），并且仅在前尖心外膜的基质放置部位观察到这种效应。相比之下，冠状动脉内注射0.3或1.0mg/kg的盐酸利多卡因导致壁增厚完全消除或被收缩期变薄所取代。因此，从聚氨酯基质心外膜给药利多卡因是治疗哇巴因诱导的室性心动过速的有效方法。基质附近的局部心肌功能仅在非常有限的程度上受到影响，这支持了基质可以安全使用而不会对心室收缩性能造成严重风险的观点。
