Quantitative relationship between plasma potassium levels and QT interval in beagle dogs.
The aim of the current study was to establish the quantitative relationship between plasma potassium concentrations and the QT interval of the electrocardiogram in dogs. Furosemide, a potent diuretic, was given at increasing doses (5-60 mg/kg) to five male and five female beagle dogs. Electrocardiogram (ECG) was recorded three times each day, simultaneous to blood sampling for measurement of plasma potassium. Furosemide treatment produced a clear hypokalaemia, which was associated with an increase in QT and corrected QT intervals (QTc) duration. On average, the slopes of the negative linear correlation between potassium plasma levels and QT or QTc were steeper in females than in males. These results show that a decrease in potassium plasma level may explain a concomitant increase in QT duration in a toxicity study in dogs, in particular if potassium values are decreased below 3.3 mmol/L. Correction of QT interval for K+ plasma level has, therefore, been established separately for males and females. A global formula correcting QT for K+ and heart rate simultaneously was established. Hypokalaemia was also associated with changes in the morphology of the T wave recorded in CV5RL, in particular, with a flattening and/or a notching of the wave (appearance of a second peak), biphasic aspect or inversion of polarity. These changes are probably related to an increased heterogeneity of repolarization between different populations of cardiomyocytes. In conclusion, hypokalaemia is quantitatively associated with an increase in QT and QTc duration in dogs. The relationship is apparently stronger for females than for males. A formula may be used to correct QT for potassium plasma level.
Hanton
G
G
Pfizer Global Research and Development, ZI Pocé-sur-Cisse, BP 159, F-37401 Amboise Cedex, France. gilles.hanton@pfizer.com
Yvon
A
A
Provost
J-P
JP
Racaud
A
A
Doubovetzky
M
M
D000818:Animals; D002118:Calcium / Q000097:blood; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D006321:Heart / Q000502:physiology*; D006339:Heart Rate; D008297:Male; D011188:Potassium / Q000097:blood*; D012964:Sodium / Q000097:blood; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology
D049994:Sodium Potassium Chloride Symporter Inhibitors; D005665:Furosemide; D012964:Sodium; D011188:Potassium; D002118:Calcium