title: Increased susceptibility of spontaneously hypertensive rats to ventricular tachyarrhythmias in early hypertension.
abstract: Hypertension is a risk factor for sudden cardiac death caused by ventricular tachycardia and fibrillation (VT/VF). We hypothesized that, in early hypertension, the susceptibility to stress-induced VT/VF increases. We compared the susceptibility of 5- to 6-month-old male spontaneously hypertensive rats (SHR) and age/sex-matched normotensive rats (NR) to VT/VF during challenge with oxidative stress (H2 O2 ; 0.15 mmol l(-1) ). We found that only SHR hearts exhibited left ventricular fibrosis and hypertrophy. H2 O2 promoted VT in all 30 SHR but none of the NR hearts. In 33% of SHR cases, focal VT degenerated to VF within 3 s. Simultaneous voltage-calcium optical mapping of Langendorff-perfused SHR hearts revealed that H2 O2 -induced VT/VF arose spontaneously from focal activations at the base and mid left ventricular epicardium. Microelectrode recording of SHR hearts showed that VT was initiated by early afterdepolarization (EAD)-mediated triggered activity. However, despite the increased susceptibility of SHR hearts to VT/VF, patch clamped isolated SHR ventricular myocytes developed EADs and triggered activity to the same extent as NR ventricular myocytes, except with larger EAD amplitude. During the early stages of hypertension, when challenged with oxidative stress, SHR hearts showed an increased ventricular arrhythmogenicity that stems primarily from tissue remodelling (hypertrophy, fibrosis) rather than cellular electrophysiological changes. Our findings highlight the need for early hypertension treatment to minimize myocardial fibrosis, ventricular hypertrophy, and arrhythmias.
authors.affiliation: UCLA Cardiovascular Research Laboratory, Division of Cardiology, Department of Medicine.
authors.forename: Thao P
authors.initials: TP
authors.lastname: Nguyen
authors.affiliation: UCLA Cardiovascular Research Laboratory, Division of Cardiology, Department of Medicine.|Present address: Department of Medicine, Cedars-Sinai Medical Centre, Los Angeles, CA, USA.
authors.forename: Ali A
authors.initials: AA
authors.lastname: Sovari
authors.affiliation: UCLA Cardiovascular Research Laboratory, Division of Cardiology, Department of Medicine.
authors.forename: Arash
authors.initials: A
authors.lastname: Pezhouman
authors.affiliation: UCLA Cardiovascular Research Laboratory, Division of Cardiology, Department of Medicine.
authors.forename: Shankar
authors.initials: S
authors.lastname: Iyer
authors.affiliation: UCLA Cardiovascular Research Laboratory, Division of Cardiology, Department of Medicine.|Present address: Department of Physiology, Wuhan University, Wuhan, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Cao
authors.affiliation: UCLA Cardiovascular Research Laboratory, Division of Cardiology, Department of Medicine.
authors.forename: Christopher Y
authors.initials: CY
authors.lastname: Ko
authors.affiliation: UCLA Cardiovascular Research Laboratory, Division of Cardiology, Department of Medicine.|Present address: Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Aneesh
authors.initials: A
authors.lastname: Bapat
authors.affiliation: UCLA Cardiovascular Research Laboratory, Division of Cardiology, Department of Medicine.|Present address: School of Pharmacy, West Coast University, Los Angeles, CA, USA.
authors.forename: Nooshin
authors.initials: N
authors.lastname: Vahdani
authors.affiliation: UCLA Cardiovascular Research Laboratory, Division of Cardiology, Department of Medicine.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Ghanim
authors.affiliation: Department of Pathology, UCLA David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Fishbein
authors.affiliation: UCLA Cardiovascular Research Laboratory, Division of Cardiology, Department of Medicine.
authors.forename: Hrayr S
authors.initials: HS
authors.lastname: Karagueuzian
mesh_terms: D000200:Action Potentials; D000818:Animals; D002478:Cells, Cultured; D005355:Fibrosis; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology; D006973:Hypertension / Q000150:complications / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017180:Tachycardia, Ventricular / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*