lipopolysaccharide induces atrial arrhythmogenesis via down-regulation of L-type Ca2+ channel genes in rats.
Septic shock has been reported as an independent risk factor for atrial fibrillation (AF), however, the mechanism remains unknown. We investigated whether lipopolysaccharide (LPS) could alter cardiac ion channel gene expression, thereby leading to atrial arrhythmogenesis. LPS (2.5 mg/kg) was injected intraperitoneally into 10 week old Sprague-Dawley rats (n = 5). Hemodynamic data were obtained and the atrial appendages were removed after LPS injection (0, 3, 6, 12, and 24 hours) for an RNase protection assay for alpha1C, beta2, alpha1G, and SCN5A. An electrophysiological study in isolated perfused hearts was performed before and 12 hours after the LPS injection. Heart rate and body temperature were significantly increased (P < 0.05) and mean blood pressure was slightly decreased (P < 0.1) at 12 hours after LPS injection. The mRNA levels of the L-type calcium channel gene (beta2 and alpha1C) were significantly decreased at 6 and 12 hours after LPS injection. Atrial ERP became significantly shortened and the number of repetitive atrial responses induced by an extrastimulus were significantly increased after LPS injection. LPS induced the down-regulation of L-type calcium channel gene expression and ERP shortening, which might be a mechanism underlying sepsis-induced AF.
Okazaki
Reiko
R
Department of Internal Medicine, Division of Cardiology, Hepatology, Geriatrics and Integrated Medicine, Nippon Medical School, Tokyo, Japan.
Iwasaki
Yu-Ki
YK
Miyauchi
Yasushi
Y
Hirayama
Yoshiyuki
Y
Kobayashi
Yoshinori
Y
Katoh
Takao
T
Mizuno
Kyoichi
K
Sekiguchi
Akiko
A
Yamashita
Takeshi
T
D000818:Animals; D001281:Atrial Fibrillation / Q000235:genetics* / Q000276:immunology; D001794:Blood Pressure / Q000235:genetics; D001833:Body Temperature Regulation / Q000235:genetics; D020746:Calcium Channels, L-Type / Q000235:genetics* / Q000276:immunology; D020747:Calcium Channels, T-Type / Q000235:genetics; D002304:Cardiac Pacing, Artificial; D015536:Down-Regulation / Q000235:genetics; D004562:Electrocardiography; D004926:Escherichia coli / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006339:Heart Rate / Q000235:genetics; D008070:Lipopolysaccharides / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012772:Shock, Septic / Q000235:genetics* / Q000276:immunology
C504728:Cacna1c protein, rat; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D008070:Lipopolysaccharides; D012333:RNA, Messenger