Dose-related effects of manganese on the canine electrocardiogram

We studied the dose-related effects of manganese, a slow channel blocker, on the ECG in seven anesthetized dogs. Incremental bolus doses of MnCl2, providing 0.1, 0.5, 1.0, 5.0, and 10.0 mg/kg Mn, were injected intravenously at sequential 10 minute intervals. Heart rate decreased from 175 +/- 5 beats/min (mean +/- SEM) to 137 +/- 6 after 5.0 mg/kg Mn (p less than .001). No significant decrease in rat occurred with lower doses. Mn at 10.0 mg/kg was lethal in six dogs following brief profound hypotension and bradycardia. The PR interval increased slightly after 0.5 mg/kg Mn, from 99 +/- 3 msec to 103 +/- 3 (p less than .01), to 106 +/- 4 msec (p less than .01) after 1.0 mg/kg, and to 117 +/- 4 msec (p less than .005) after 5.0 mg/kg. QRS width increased from 57 +/- 2 msec to 65 +/- 1 (p less than .005) after 1.0 mg/kg Mn and was not further prolonged after 5.0 mg/kg. The observed QT interval increased from 186 +/- 2 msec to 201 +/- 1 (p less than .025) after 1.0 mg/kg Mn and to 222 +/- 2 (p less than .01) after 5.0 mg/kg. The rate-corrected QT interval was also increased at these doses. These data suggest that important in vivo effects of manganese on atrioventricular and intraventricular conduction occur at doses which do not affect the heart rate.