Hyperventilation assists proarrhythmia development during delayed repolarization in clofilium-treated, anaesthetized,...

Hyperventilation reduces partial pressure of CO₂ (PCO₂) in the blood, which results in hypokalaemia. Hypokalaemia helps the development of the life-threatening torsades de pointes type ventricular arrhythmia (TdP) evoked by repolarization delaying drugs. This implies that hyperventilation may assist the development of proarrhythmic events. Therefore, this study experimentally investigated the effect of hyperventilation on proarrhythmia development during delayed repolarization. Phenylephrine (an α₁-adrenoceptor agonist) and clofilium (as a representative repolarization delaying agent inhibiting the rapid component of the delayed rectifier potassium current, I_Kr) were administered intravenously to pentobarbital-anaesthetized, mechanically ventilated, open chest rabbits. ECG was recorded, and the onset times and incidences of the arrhythmias were determined. Serum K⁺, pH and PCO₂ were measured in arterial blood samples. Clofilium prolonged the rate corrected QT interval. TdP occurred in 15 animals (TdP+ group), and did not occur in 14 animals (TdP- group). We found a strong, positive, linear correlation between serum K⁺ and PCO₂. There was no relationship between the occurrence of TdP and the baseline K⁺ and PCO₂ values. However, a positive, linear correlation was found between the onset time of the first arrhythmias and the K⁺ and PCO₂ values. The regression lines describing the relationship between PCO₂ and onset time of first arrhythmias were parallel in the TdP+ and TdP- groups, but the same PCO₂ resulted in earlier arrhythmia onset in the TdP+ group than in the TdP- group. We conclude that hyperventilation and hypocapnia with the resultant hypokalaemia assist the multifactorial process of proarrhythmia development during delayed repolarization. This implies that PCO₂ and serum K⁺ should be controlled tightly during mechanical ventilation in experimental investigations and clinical settings when repolarization-delaying drugs are applied.