Antiarrhythmic vs. pro-arrhythmic effects depending on the intensity of adrenergic stimulation in a canine anthopleurin-A model of type-3 long QT syndrome.
OBJECTIVE
The effects of adrenergic activity and beta-blockade were studied in a canine experimental model of type-3 long QT syndrome (LQT3) induced by application of anthopleurin-A.


RESULTS
Boluses of epinephrine at 0.5 and/or 1.0 microg/kg were administered before and after propranolol, 0.3 mg/kg, and the distribution of the ventricular repolarization and the development of polymorphic ventricular tachyarrhythmia (VA) were assessed. Using needle electrodes, transmural unipolar electrograms were recorded across the left ventricle (LV) and right ventricle (RV). Activation-recovery interval (ARI) was measured in each electrogram to estimate local repolarization during RV pacing at the cycle length of 750 ms after the creation of complete atrioventricular block. Before propranolol, epinephrine, 0.5 microg/kg, did not induce VA in any experiment. However, a dose of 1.0 microg/kg induced polymorphic VA following multiple premature ventricular complex (PVC) in four of six experiments. Epinephrine, 0.5 microg/kg, shortened ARI at all sites and lessened LV transmural ARI dispersion. Neither ARI nor its dispersion could be determined after 1.0 microg/kg of epinephrine because of the induction of PVC, polymorphic VA, or both. Propranolol (i) prevented epinephrine-induced PVC and polymorphic VA in all experiments, (ii) slightly prolonged ARI at all sites, along with a decrease in LV transmural ARI dispersion, and (iii) reversed the epinephrine-induced shortening of ARI.


CONCLUSIONS
In this LQT3 model, an increase in adrenergic activity by epinephrine had dose-dependent, opposite effects on ventricular electrical stability. Since beta-adrenergic blockade suppressed epinephrine-induced PVC and polymorphic VA, it might be considered for supplemental therapy to suppress VA in patients presenting with LQT3.
Chinushi
Masaomi
M
School of Health Science, Niigata University School of Medicine, 2-746 Asahimachi, Nigata 951-8518, Japan. masaomi@clg.niigata-u.ac.jp
Izumi
Daisuke
D
Iijima
Kenichi
K
Ahara
Shizue
S
Komura
Satoru
S
Furushima
Hiroshi
H
Hosaka
Yukio
Y
Aizawa
Yoshifusa
Y
D000322:Adrenergic Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D004837:Epinephrine / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins; D008133:Long QT Syndrome / Q000209:etiology / Q000503:physiopathology*; D010455:Peptides; D011433:Propranolol / Q000494:pharmacology*; D011941:Receptors, Adrenergic / Q000502:physiology; D016276:Ventricular Function / Q000187:drug effects*
D000322:Adrenergic Agonists; D000319:Adrenergic beta-Antagonists; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D011941:Receptors, Adrenergic; C012746:anthopleurin-A; D011433:Propranolol; D004837:Epinephrine