Aims: 

The most frequently used in vivo proarrhythmia model utilizes anaesthetized, artificially ventilated rabbits. It is not known whether artificial ventilation influences the onset of drug-induced arrhythmias. Thus, the purpose of the present study was to examine the relationship between artificial ventilation, blood gas parameters and the onset of drug-induced arrhythmias.

Methods: 

The delayed rectifier potassium current inhibitor clofilium and the a1 adrenoceptor agonist phenylephrine were administered to Na-pentobarbital-anaesthetized rabbits (n=29 animals). ECG was recorded during the experiments. From the ECG, the time to onset and the incidence of arrhythmias were determined. The serum potassium level, the pH and the partial pressures of CO₂ and O₂ (pCO₂ and pO₂, respectively) were measured from arterial blood samples. Animals that experienced clofilium-induced torsades de pointes tachyarrhythmia (TdP) were retrospectively allocated to a 'TdP^+' group (n=15 animals); animals that did not experience clofilium-induced TdP were retrospectively allocated to a 'TdP^-' group (n=14 animals).

Results: 

A close linear correlation was revealed between the baseline, drug-free pCO₂ values and the serum potassium levels. No relationship was found between the occurrence of TdP and the baseline, drug-free potassium levels and the pCO₂ values. On the other hand, baseline pCO₂ and serum potassium levels determined the onset time of the first, drug-induced arrhythmias; there was a linear relationship between the onset time of the first arrhythmias and the baseline pCO₂ and serum potassium levels. However, the regression lines of the 'TdP^+' and the 'TdP^-' groups were parallel, the same baseline potassium levels and pCO₂ values resulted in earlier onset of the first arrhythmias in the 'TdP^+' group than in the 'TdP^-' group.

Conclusions: 

Hyperventilation induces respiratory alkalosis and hypokalaemia, which promote occurrence of clofilium-induced arrhythmias in anaesthetized rabbits. Also, other factors, which are independent from the respiratory status, contribute to the development of first arrhythmias and TdP.