Class III antiarrhythmic effects of ceruloplasmin on rat heart.
Recently it has been shown that ceruloplasmin presents a protective action against reperfusion-induced arrhythmias in the isolated perfused rat heart, an effect that is lost when the protein is denaturated by heat. The present study was carried out to see whether ceruloplasmin can alter electrophysiological properties such as ventricular effective refractory periods, conduction time, and action potential duration calculated at 50, 75, and 90% levels of repolarization (APD50, APD75, APD90). To check the specificity of the electrophysiological effects of ceruloplasmin, we have also compared them with those of heat-denatured ceruloplasmin, superoxide dismutase, catalase, deferoxamine, and albumin. In isolated rat hearts, ceruloplasmin (0.25-3 microM) (n = 8 for each concentration) was shown to increase the effective refractory period in a concentration-dependent manner by 26 to 89%. Conduction time was not significantly altered. Heat-denatured ceruloplasmin (0.50-3 microM) (n = 8 for each concentration) increased the effective refractory period by 33 to 70% and did not affect the conduction time. In contrast, superoxide dismutase (1-4 microM), catalase (1-2 microM), deferoxamine (500 microM-1 mM), and albumin (1-4 microM) (n = 8 for each substance and for each concentration) had no significant effect on effective refractory period and conduction time at any dose, suggesting that the ceruloplasmin effect might be specific. In rat ventricular preparations, ceruloplasmin (1 microM) also induced a constant prolongation of APD50 (52%), APD75 (64%), and APD90 (41%) after 15 min of infusion (n = 6). The prolongation of effective refractory period and of action potential duration, by native and heat-denatured ceruloplasmin, suggests that this substance has specific class III effects, although this cannot entirely account for its antifibrillatory action at reperfusion in isolated rat hearts.
Department of Physiology, Université de Montréal, Canada.
R
R
Atanasiu
L
L
Gouin
M A
MA
Mateescu
R
R
Cardinal
R
R
Nadeau
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002570:Ceruloplasmin / Q000494:pharmacology*; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012032:Refractory Period, Electrophysiological
D000889:Anti-Arrhythmia Agents; D002570:Ceruloplasmin