Age-dependent atrial remodeling induced by recombinant human interleukin-11: implications for atrial flutter/fibrillation.
Recombinant human interleukin-11 (rhIL-11) has been used to alleviate side effects caused by chemotherapy in patients with neoplastic diseases and as an experimental anti-inflammatory agent. Its use in elderly patients has been associated with increased frequency of atrial flutter/fibrillation (AF). The mechanism of the latter phenomenon was studied in a rat model in vivo. Adult and old Fischer 344 rats fed with either normal diet or sodium-restricted diets were treated with rhIL-11 or vehicle (control) (1 mg/kg/day, i.p., 7 days); cardiac electrophysiologic parameters and atrial dimensions were determined. In adult rats, rhIL-11 was without effect, and atrial pacing did not induce AF. In contrast, in old rats, rhIL-11 shortened atrial refractoriness and increased atrial dimensions. Also, atrial pacing induced AF in old rats treated with rhIL-11 more than in controls. These effects of rhIL-11 in old rats were reversed by sodium-restricted diet. It was concluded that rhIL-11 induces age-dependent atrial remodeling manifested by atrial stretch and reduced atrial refractoriness, which favor AF. Na retention is the most likely mechanism underlying this effect of rhIL-11.
Xu
Jiang
J
MCP Hahnemann University, Philadelphia, Pennsylvania 19102-1192, USA.
Ren
Jian-Fang
JF
Mugelli
Alessandro
A
Belardinelli
Luiz
L
Keith Jr
James C
JC
Pelleg
Amir
A
D000367:Age Factors; D000818:Animals; D001281:Atrial Fibrillation / Q000139:chemically induced; D001282:Atrial Flutter / Q000139:chemically induced; D016275:Atrial Function / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D004039:Diet, Sodium-Restricted; D004562:Electrocardiography; D004594:Electrophysiology; D006325:Heart Atria / Q000473:pathology / Q000503:physiopathology; D006352:Heart Ventricles / Q000503:physiopathology; D017370:Interleukin-11 / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000009:adverse effects* / Q000494:pharmacology
D017370:Interleukin-11; D011994:Recombinant Proteins