Komadina K H, Carlson T A, Strollo P J, Navratil D L
Department of Medicine, Wilford Hall US Air Force Medical Center, San Antonio.
Chest. 1992 Jan;101(1):232-8. doi: 10.1378/chest.101.1.232.
Aminophylline and beta-adrenergic agonists are widely used in the treatment of obstructive lung diseases. It has been suggested that combined aminophylline and beta-agonist therapy may promote the development of atrial and ventricular arrhythmias. The effects of these agents in combination on myocardial conduction and tissue refractoriness have not been documented. We evaluated the electrophysiologic effects of intravenous aminophylline and inhaled metaproterenol on canine myocardium. Aminophylline produced significant decreases from baseline in the AH interval (85 +/- 6.5 [SD] to 63 +/- 4.1 ms [p less than 0.02]), Wenckebach cycle length (WCL) (226 +/- 8.7 to 182 +/- 5.8 ms [p less than 0.02]), and ventricular effective refractory period (VERP) (166 +/- 6.0 to 148 +/- 4.9 ms [p less than 0.01]). Metaproterenol produced similar results, except metaproterenol significantly decreased the atrial effective refractory period (AERP) from 152 +/- 6.6 to 130 +/- 3.2 ms (p less than 0.02), an effect not seen with aminophylline alone. Metaproterenol also produced significantly greater reductions in AH interval and WCL, as well as a greater increase in heart rate than aminophylline did. When compared with aminophylline alone, combined metaproterenol and aminophylline therapy produced significantly greater reductions in the AH interval (63 +/- 4.1 versus 48 +/- 1.2 ms for combined therapy [p less than 0.01]), HV interval (32 +/- 1.2 versus 28 +/- 2.0 ms for combined therapy [p less than 0.02]), WCL (182 +/- 5.8 versus 150 +/- 7.1 ms for combined therapy [p less than 0.02]), and VERP (148 +/- 4.9 versus 132 +/- 2.0 ms for combined therapy [p less than 0.02]). We conclude that both aminophylline and metaproterenol significantly enhance AV nodal and His-Purkinje conduction. Metaproterenol produced significant changes in both atrial and ventricular tissue refractoriness. Metaproterenol produced significantly greater changes than aminophylline alone, and inhaled metaproterenol combined with intravenous aminophylline produced greater changes in AV nodal and His-Purkinje conduction and ventricular refractoriness than did aminophylline alone in a canine model.
氨茶碱和β-肾上腺素能激动剂广泛用于治疗阻塞性肺疾病。有人提出，氨茶碱和β-激动剂联合治疗可能会促进房性和室性心律失常的发生。这些药物联合使用对心肌传导和组织不应期的影响尚未见报道。我们评估了静脉注射氨茶碱和吸入间羟异丙肾上腺素对犬心肌的电生理作用。氨茶碱使AH间期（从85±6.5[标准差]降至63±4.1毫秒[p<0.02]）、文氏周期长度（WCL）（从226±8.7降至182±5.8毫秒[p<0.02]）和心室有效不应期（VERP）（从166±6.0降至148±4.9毫秒[p<0.01]）较基线值显著降低。间羟异丙肾上腺素产生了类似的结果，不过间羟异丙肾上腺素使心房有效不应期（AERP）从152±6.6显著降至130±3.2毫秒（p<0.02），单独使用氨茶碱时未观察到这种效应。间羟异丙肾上腺素在AH间期和WCL方面的降低幅度也显著大于氨茶碱，且心率增加幅度更大。与单独使用氨茶碱相比，间羟异丙肾上腺素与氨茶碱联合治疗使AH间期（联合治疗为63±4.1毫秒，单独氨茶碱治疗为48±1.2毫秒[p<0.01]）、HV间期（联合治疗为32±1.2毫秒，单独氨茶碱治疗为28±2.0毫秒[p<0.02]）、WCL（联合治疗为182±5.8毫秒，单独氨茶碱治疗为150±7.1毫秒[p<0.02]）和VERP（联合治疗为148±4.9毫秒，单独氨茶碱治疗为132±2.0毫秒[p<0.02]）的降低幅度更大。我们得出结论，氨茶碱和间羟异丙肾上腺素均能显著增强房室结和希氏-浦肯野系统的传导。间羟异丙肾上腺素使心房和心室组织不应期均发生了显著变化。间羟异丙肾上腺素产生的变化比单独使用氨茶碱时显著更大，在犬模型中，吸入间羟异丙肾上腺素与静脉注射氨茶碱联合使用在房室结和希氏-浦肯野系统传导以及心室不应期方面产生的变化比单独使用氨茶碱时更大。
