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

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, IKr) 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.

Epitope mapping of human ETS1 monoclonal antibody.

The epitope for E44 monoclonal antibody (mAb) was mapped using mutated ETS1 proteins lacking different carboxy-terminal regions and by the employment of synthetic oligopeptides spanning the epitope region. This epitope lies around Arg211 of the human ETS1 protein since substitution of Arg211 by Gln211 in the epitope region results in the loss of recognition of the mouse ETS1 protein by E44 mAb. Substitution of Leu214 by valine214 in the epitope region (as is found in the chicken ETS1 and viral Ets proteins) does not alter the capacity of the E44 mAb to recognize this antigen. Taken together, these results suggest that a specific ionic interaction is able to play a pivotal role in the recognition of the ETS1 protein by the E44 mAb.