Mechanism of cardiac arrhythmias induced by epinephrine in dogs with hypokalemia

Ajioka, M.; Sugiyama, S.; Ogawa, K.; Satake, T.; Ozawa, T.

Journal of the American College of Cardiology 8(6): 1373-1379


ISSN/ISBN: 0735-1097
PMID: 3782641
DOI: 10.1016/s0735-1097(86)80310-2
Accession: 005866799

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To investigate the mechanism of ventricular arrhythmias induced by epinephrine in dogs with hypokalemia, 30 adult mongrel dogs were separated into a control group (n=13) and a hypokalemia group (n=17). In the hypokalemia group, sodium polystyrene sulfonate (5 g/kg body weight) was infused into the colon. In both groups, the serum concentrations of sodium, potassium and calcium were measured every 15 minutes for 60 minutes. The mean (.+-. standard deviation) serum potassium level of the hypokalemia group decreased significantly from 3.81 .+-. 0.21 to 2.92 .+-. 0.36 mEq/liter; there were no significant changes in other electrolytes. After 60 minutes, epinephrine (10 .mu.g/kg) was injected intravenously in the hypokalemia and control groups, and the arrhythmia ratio (the number of ventricular ectopic beats divided by the total heart rate) was calculated for 5 minutes. Each group was further classified into subgroups of dogs with an arrhythmia ratio higher or lower than 10%. An arrhythmia ratio over 10% was observed in 7.7% of the control group and 53% of the hypokalemia group. Immediately after 5 minutes of epinephrine injection, myocardial mitochondria and plasma membrane fraction were prepared from each group. Mitochondrial calcium content and phospholipase activity of plasma membrane fraction were determined. Significant increases in both mitochondrial calcium content and phospholipase activity were observed in the dogs with hypokalemia and an arrhythmia ratio greater than 10%. In the hypokalemia group, there was a clear reciprocal correlation (r=-0.79) between serum potassium concentration at 60 minutes and mitochondrial calcium content, and a clear correlation (r=0.80) between mitochondrial calcium content and phospholipase activity. It was also demonstrated that the dogs with a higher than 10% arrhythmia ratio had a low serum potassium concentration, high mitochondrial calcium content and high phospholipase activity. These results suggest that hypokalemia enhances the calcium influx induced by epinephrine, resulting in activation of phospholipase, which is responsible for the development of ventricular arhythmias.