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). CONCLUSION: 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.
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). CONCLUSION: 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.
Authors: Angela Sciacqua; Maria Perticone; Giovanni Tripepi; Eliezer J Tassone; Antonio Cimellaro; Deborah Mazzaferro; Giorgio Sesti; Francesco Perticone Journal: Intern Emerg Med Date: 2015-05-05 Impact factor: 3.397
Authors: Nisha Bansal; Leila R Zelnick; Alvaro Alonso; Emelia J Benjamin; Ian H de Boer; Rajat Deo; Ronit Katz; Bryan Kestenbaum; Jehu Mathew; Cassianne Robinson-Cohen; Mark J Sarnak; Michael G Shlipak; Nona Sotoodehnia; Bessie Young; Susan R Heckbert Journal: Clin J Am Soc Nephrol Date: 2017-08-10 Impact factor: 8.237
Authors: Jason H Y Wu; Roberto Marchioli; Maria G Silletta; Serge Masson; Frank W Sellke; Peter Libby; Ginger L Milne; Nancy J Brown; Federico Lombardi; Ralph J Damiano; Joann Marsala; Mauro Rinaldi; Alberto Domenech; Caterina Simon; Luigi Tavazzi; Dariush Mozaffarian Journal: J Am Heart Assoc Date: 2015-05-20 Impact factor: 5.501
Authors: Alexander J Kula; Ronit Katz; Leila R Zelnick; Elsayed Soliman; Alan Go; Michael Shlipak; Rajat Deo; Bonnie Ky; Ian DeBoer; Amanda Anderson; Rob Christenson; Stephen L Seliger; Chris Defilippi; Harold I Feldman; Myles Wolf; John Kusek; Tariq Shafi; Jiang He; Nisha Bansal Journal: Nephrol Dial Transplant Date: 2021-12-02 Impact factor: 5.992