Hanton G, Yvon A, Provost J-P, Racaud A, Doubovetzky M
Pfizer Global Research and Development, ZI Pocé-sur-Cisse, BP 159, F-37401 Amboise Cedex, France.
Lab Anim. 2007 Apr;41(2):204-17. doi: 10.1258/002367707780378050.
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.
本研究的目的是确定犬血浆钾浓度与心电图QT间期之间的定量关系。给5只雄性和5只雌性比格犬递增剂量(5 - 60 mg/kg)给予强效利尿剂呋塞米。每天记录3次心电图(ECG),同时采集血样以测量血浆钾。呋塞米治疗导致明显的低钾血症,这与QT和校正QT间期(QTc)持续时间增加有关。平均而言,雌性犬血浆钾水平与QT或QTc之间的负线性相关斜率比雄性犬更陡。这些结果表明,在犬的毒性研究中,血浆钾水平降低可能解释QT持续时间的相应增加,特别是当钾值降至3.3 mmol/L以下时。因此,已分别为雄性和雌性建立了根据血浆钾水平校正QT间期的公式。建立了一个同时根据钾和心率校正QT的通用公式。低钾血症还与CV5RL记录的T波形态变化有关,特别是波的平坦和/或切迹(出现第二个峰)、双相形态或极性反转。这些变化可能与不同心肌细胞群体之间复极化异质性增加有关。总之,低钾血症与犬QT和QTc持续时间增加在数量上相关。这种关系在雌性中显然比在雄性中更强。可使用一个公式根据血浆钾水平校正QT。