Establishment of a model of atrial fibrillation associated with chronic kidney disease in rats and the role of oxidative stress.
BACKGROUND
An animal model of atrial fibrillation (AF) associated with chronic kidney disease (CKD) has not been available.


OBJECTIVE
The purpose of this study was to test the validity of 5/6 nephrectomy (5.6Nx) as an appropriate model of AF associated with CKD and to investigate the role of oxidative stress.


METHODS
Male Sprague-Dawley rats were subjected to 5.6Nx. A novel derivative of lipoic acid, sodium zinc dihydrolipoylhistidinate (DHLHZn), was subcutaneously infused. Four weeks later, hearts were isolated.


RESULTS
We observed 5 main findings. (1) 5.6Nx induced renal dysfunction with elevation of systolic blood pressure and impaired glucose tolerance. (2) In the left atrium (LA), expressions of α-smooth muscle action and collagen type I, the compositional proteins of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and malondialdehyde were increased by 5.6Nx, which was reversed by DHLHZn treatment. (3) In the LA, the tissue content of angiotensin II was elevated by 5.6Nx, which was also reversed by DHLHZn. (4) Masson trichrome staining revealed that heterogeneous LA interstitial fibrosis was induced by 5.6Nx, which was attenuated by DHLHZn. (5) In isolated perfused heart experiments, 5.6Nx caused slowing of interatrial conduction. In the hearts of rats of the 5.6Nxgroup, right atrial extrastimuli invariably induced AF (8/8 [100%]), which were suppressed by DHLHZn (3/8 [38%], P <.05).


CONCLUSIONS
We successfully established an appropriate model of AF associated with CKD in rats. Because the amount of NADPH oxidase was increased and the potent antioxidant agent DHLHZn was effective, oxidative stress may be involved in the pathogenesis of LA fibrosis and enhanced AF vulnerability in our model.
Department of Internal Medicine 1, Oita University Faculty of Medicine, Oita, Japan.
Naoya
N
Fukunaga
Naohiko
N
Takahashi
Satoshi
S
Hagiwara
Osamu
O
Kume
Akira
A
Fukui
Yasushi
Y
Teshima
Tetsuji
T
Shinohara
Tomoko
T
Nawata
Masahide
M
Hara
Takayuki
T
Noguchi
Tetsunori
T
Saikawa
D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D001794:Blood Pressure; D004195:Disease Models, Animal; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000378:metabolism