Rotigaptide (ZP123) reverts established atrial conduction velocity slowing.
Rotigaptide (ZP123) increases gap junction intercellular communication (GJIC) and prevents stress-induced cardiac conduction velocity (CV) slowing. However, the effect of rotigaptide on established cardiac conduction slowing and the duration of effect on rotigaptide during washout is unknown. Metabolic stress (induced by superfusion with nonoxygenated glucose-free Tyrodes buffer) was associated with a 30% decrease in atrial CV in vehicle-treated rat atria. Rotigaptide treatment initiated after a period of 30 minutes of metabolic stress produced a rapid and significant increase in CV compared to vehicle-treated time controls. During washout of rotigaptide for 30 min (while subjected to metabolic stress), there was a minor decrease in atrial CV; however, this was not significantly different from atrial CV in a rotigaptide-treated time control group. Rotigaptide treatment rapidly normalizes established conduction slowing in atria subjected to metabolic stress. However, the cessation of effect was considerably slower than the onset of action.
Haugan
Ketil
K
Zealand Pharma A/S, Smedeland 26B, DK-2600, Glostrup, Denmark.
Kjølbye
Anne Louise
AL
Hennan
James K
JK
Petersen
Jørgen Søberg
JS
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000503:physiopathology; D006325:Heart Atria / Q000187:drug effects* / Q000503:physiopathology; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction; D009842:Oligopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D009842:Oligopeptides; C477643:rotigaptide