title: Hyperventilation assists proarrhythmia development during delayed repolarization in clofilium-treated, anaesthetized, mechanically ventilated rabbits.
abstract: 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 PCO2were 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 PCO2values. However, a positive, linear correlation was found between the onset time of the first arrhythmias and the K+and PCO2values. The regression lines describing the relationship between PCO2and onset time of first arrhythmias were parallel in the TdP+ and TdP- groups, but the same PCO2resulted 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 PCO2and serum K+should be controlled tightly during mechanical ventilation in experimental investigations and clinical settings when repolarization-delaying drugs are applied.
authors.affiliation: Second Department of Medicine and Cardiology Centre, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: H
authors.initials: H
authors.lastname: Papp
authors.affiliation: Department of Anaesthesiology and Intensive Therapy, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Sarusi
authors.affiliation: Second Department of Medicine and Cardiology Centre, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: A S
authors.initials: AS
authors.lastname: Farkas
authors.affiliation: Second Department of Medicine and Cardiology Centre, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: H
authors.initials: H
authors.lastname: Takacs
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: P
authors.initials: P
authors.lastname: Kui
authors.affiliation: Second Department of Medicine and Cardiology Centre, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: D
authors.initials: D
authors.lastname: Vincze
authors.affiliation: Second Department of Medicine and Cardiology Centre, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: E
authors.initials: E
authors.lastname: Ivany
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary.|MTA-SZTE Research Group for Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Varro
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary.|MTA-SZTE Research Group for Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: J G
authors.initials: JG
authors.lastname: Papp
authors.affiliation: Second Department of Medicine and Cardiology Centre, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: T
authors.initials: T
authors.lastname: Forster
authors.affiliation: Second Department of Medicine and Cardiology Centre, Faculty of Medicine, University of Szeged, Szeged, Hungary. farkas.andras@med.u-szeged.hu.
authors.forename: A
authors.initials: A
authors.lastname: Farkas
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D001785:Blood Gas Monitoring, Transcutaneous; D004562:Electrocardiography; D006985:Hyperventilation / Q000097:blood / Q000503:physiopathology*; D007008:Hypokalemia / Q000097:blood / Q000503:physiopathology*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000097:blood; D026902:Potassium Channel Blockers / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D011817:Rabbits; D012121:Respiration, Artificial
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D000889:Anti-Arrhythmia Agents; D026902:Potassium Channel Blockers; D000644:Quaternary Ammonium Compounds; D010656:Phenylephrine; C022799:clofilium; D011188:Potassium