BACKGROUND: There is a lack of understanding of the substrate for microreentrant circuits and triggered activity of the pulmonary vein (PV) muscle sleeves and atria in patients with atrial fibrillation (AF). OBJECTIVE: This study sought to examine the histological substrate of patients with chronic AF. METHODS: We stained 23 biopsies taken from the PV-left atrium (LA) junction and right atrial appendage from 5 chronic AF patients and 3 sinus rhythm (SR) patients undergoing mitral valve surgery using periodic acid-Schiff (PAS) test, and antibodies to hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 (HCN4), CD117/c-kit, myoglobin, tyrosine hydroxylase (TH), growth-associated protein 43, cholineacetyltransferase, and synaptophysin, as well as trichrome. RESULTS: As opposed to being clustered together in the subendocardial layer in SR patients, PAS-positive cells were separated from each other by inflammatory infiltrate and collagen fibers in AF patients. These cells stained positively for HCN4 and myoglobin, indicating they were cardiomyocytes that might have a potential pacemaking function, but different from CD117/c-kit-positive interstitial Cajal-like cells (ICLC). In AF patients, the intercellular space was occupied by a lymphomononuclear infiltrate (100% vs 33% in SR patients, P = .002), and a greater amount of interstitial fibrosis (37% +/- 5.6% vs 7.4% +/- 2.8%, P = .009). Nerve densities did not differ between AF and SR patients. However, the density of sympathetic nerve twigs in AF patients was significantly greater as compared to the others nerves (P = .03). CONCLUSION: HCN4-/PAS-positive cardiomyocytes and CD117/c-kit-positive ICLC scattered among abundant inflammatory infiltrate, fibrous tissue, and sympathetic nerve structures in the atria and at the PV-LA junctions might be a substrate for the maintenance of chronic AF.
BACKGROUND: There is a lack of understanding of the substrate for microreentrant circuits and triggered activity of the pulmonary vein (PV) muscle sleeves and atria in patients with atrial fibrillation (AF). OBJECTIVE: This study sought to examine the histological substrate of patients with chronic AF. METHODS: We stained 23 biopsies taken from the PV-left atrium (LA) junction and right atrial appendage from 5 chronic AFpatients and 3 sinus rhythm (SR) patients undergoing mitral valve surgery using periodic acid-Schiff (PAS) test, and antibodies to hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 (HCN4), CD117/c-kit, myoglobin, tyrosine hydroxylase (TH), growth-associated protein 43, cholineacetyltransferase, and synaptophysin, as well as trichrome. RESULTS: As opposed to being clustered together in the subendocardial layer in SR patients, PAS-positive cells were separated from each other by inflammatory infiltrate and collagen fibers in AFpatients. These cells stained positively for HCN4 and myoglobin, indicating they were cardiomyocytes that might have a potential pacemaking function, but different from CD117/c-kit-positive interstitial Cajal-like cells (ICLC). In AFpatients, the intercellular space was occupied by a lymphomononuclear infiltrate (100% vs 33% in SR patients, P = .002), and a greater amount of interstitial fibrosis (37% +/- 5.6% vs 7.4% +/- 2.8%, P = .009). Nerve densities did not differ between AF and SR patients. However, the density of sympathetic nerve twigs in AFpatients was significantly greater as compared to the others nerves (P = .03). CONCLUSION:HCN4-/PAS-positive cardiomyocytes and CD117/c-kit-positive ICLC scattered among abundant inflammatory infiltrate, fibrous tissue, and sympathetic nerve structures in the atria and at the PV-LA junctions might be a substrate for the maintenance of chronic AF.
Authors: Kalyanam Shivkumar; Olujimi A Ajijola; Inder Anand; J Andrew Armour; Peng-Sheng Chen; Murray Esler; Gaetano M De Ferrari; Michael C Fishbein; Jeffrey J Goldberger; Ronald M Harper; Michael J Joyner; Sahib S Khalsa; Rajesh Kumar; Richard Lane; Aman Mahajan; Sunny Po; Peter J Schwartz; Virend K Somers; Miguel Valderrabano; Marmar Vaseghi; Douglas P Zipes Journal: J Physiol Date: 2016-06-14 Impact factor: 5.182
Authors: Ayaka Numata; Yasushi Miyauchi; Norihiko Ono; Michael C Fishbein; William J Mandel; Shien-Fong Lin; James N Weiss; Peng-Sheng Chen; Hrayr S Karagueuzian Journal: J Cardiovasc Electrophysiol Date: 2011-10-28
Authors: Daniel A Gil; Luther M Swift; Huda Asfour; Narine Muselimyan; Marco A Mercader; Narine A Sarvazyan Journal: J Biophotonics Date: 2016-08-22 Impact factor: 3.207
Authors: Georg Gussak; Anna Pfenniger; Lisa Wren; Mehul Gilani; Wenwei Zhang; Shin Yoo; David A Johnson; Amy Burrell; Brandon Benefield; Gabriel Knight; Bradley P Knight; Rod Passman; Jeffrey J Goldberger; Gary Aistrup; J Andrew Wasserstrom; Yohannes Shiferaw; Rishi Arora Journal: JCI Insight Date: 2019-10-17