Antiarrhythmic effect of manganese chloride in infarcted dogs with observations on the dose-related response of heart rate and ventricular pressure
The dose-related effects of MnCl2 on heart rate (HR) and peak left ventricular pressure (LVP) in adult anesthetized dogs were studied. These data were used to examine the effect of MnCl2 on ventricular premature complexes (VPCs) appearing 4 and 24 hr after myocardial infarction produced by percutaneous selective coronary embolization. Continuous electrocardiographic recording allowed VPCs to be counted each minute, rather than sampled. For statistical analysis, the mean VPC frequency over a continuous 15-min period preceding MnCl2 injection was compared with the mean frequency during the continuous 15-min period that followed. As the dose of Mn (as MnCl2) was increased from 0.1 to 10 mg/kg, HR and LVP did not decrease until 1 mg/kg was exceeded. In eight nonischemic dogs, 1 mg/kg of Mn produced no significant change in HR (175 ± 5-173 ± 6 beats/min, mean ± S.E.M.) or LVP (164 ± 7-158 ± 7 mm Hg). With 5 mg/kg, HR fell to 137 ± 6 (P<.001) and LVP to 130 ± 8 (P<.005). In three infarcted dogs, 3 mg/kg of Mn given over 5 min produced a 9% decrease in HR and 22% decrease in LVP lasting for 30 to 60 min. Mn immediately reduced ventricular ectopy in all dogs. In seven dogs studied 4 hr after infarction, 3 mg/kg given over 5 min reduced the mean frequency of VPCs from 59 ± 27 to 28 ± 22 per minute (P<.02 by Wilcoxon paired sign rank). At 24 hr after infarction, Mn reduced the mean VPC frequency from 121 ± 23 to 61 ± 26 (P<.02). We conclude that MnCl2, a calcium antagonist, has potentially useful antiarrhythmic properties in the acute ischemic setting. Although the mechanism by which Mn reduces ventricular ectopy remains speculative, these data are consistent with the hypothesis that the slow response is relevant to ischemic arrhythmogenesis.