title: Spontaneous ventricular fibrillation in right ventricular failure secondary to chronic pulmonary hypertension.
abstract: BACKGROUND
  Right ventricular failure (RVF) in pulmonary hypertension (PH) is associated with increased incidence of sudden death by a poorly explored mechanism. We test the hypothesis that PH promotes spontaneous ventricular fibrillation (VF) during a critical post-PH onset period characterized by a sudden increase in mortality.
  
  
  RESULTS
  Rats received either a single subcutaneous dose of monocrotaline (MCT, 60 mg/kg) to induce PH-associated RVF (PH, n=24) or saline (control, n=17). Activation pattern of the RV-epicardial surface was mapped using voltage-sensitive dye in isolated Langendorff-perfused hearts along with single glass-microelectrode and ECG-recordings. MCT-injected rats developed severe PH by day 21 and progressed to RVF by approximately day 30. Rats manifested increased mortality, and ≈30% rats died suddenly and precipitously during 23-32 days after MCT. This fatal period was associated with the initiation of spontaneous VF by a focal mechanism in the RV, which was subsequently maintained by both focal and incomplete reentrant wave fronts. Microelectrode recordings from the RV-epicardium at the onset of focal activity showed early afterdepolarization-mediated triggered activity that led to VF. The onset of the RV cellular triggered beats preceded left ventricular depolarizations by 23±8 ms. The RV but not the left ventricular cardiomyocytes isolated during this fatal period manifested significant action potential duration prolongation, dispersion, and an increased susceptibility to depolarization-induced repetitive activity. No spontaneous VF was observed in any of the control hearts. RVF was associated with significantly reduced RV ejection fraction (P<0.001), RV hypertrophy (P<0.001), and RV fibrosis (P<0.01). The hemodynamic function of the LV and its structure were preserved.
  
  
  CONCLUSIONS
  PH-induced RVF is associated with a distinct phase of increased mortality characterized by spontaneous VF arising from the RV by an early afterdepolarization-mediated triggered activity.
authors.affiliation: Department of Anesthesiology, UCLA School of Medicine, BH-160CHS, 650 Charles Young Dr, Los Angeles, CA 90095-7115, USA. meghbali@ucla.edu
authors.forename: Soban
authors.initials: S
authors.lastname: Umar
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Lee
authors.forename: Enno
authors.initials: E
authors.lastname: de Lange
authors.forename: Andrea
authors.initials: A
authors.lastname: Iorga
authors.forename: Rod
authors.initials: R
authors.lastname: Partow-Navid
authors.forename: Aneesh
authors.initials: A
authors.lastname: Bapat
authors.forename: Arnoud
authors.initials: A
authors.lastname: van der Laarse
authors.forename: Rajeev
authors.initials: R
authors.lastname: Saggar
authors.forename: Rajan
authors.initials: R
authors.lastname: Saggar
authors.forename: Dirk L
authors.initials: DL
authors.lastname: Ypey
authors.forename: Hrayr S
authors.initials: HS
authors.lastname: Karagueuzian
authors.forename: Mansoureh
authors.initials: M
authors.lastname: Eghbali
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D004562:Electrocardiography; D005500:Follow-Up Studies; D006333:Heart Failure / Q000150:complications* / Q000503:physiopathology; D006339:Heart Rate / Q000502:physiology; D006976:Hypertension, Pulmonary / Q000150:complications* / Q000503:physiopathology; D008297:Male; D011379:Prognosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018497:Ventricular Dysfunction, Right / Q000150:complications* / Q000503:physiopathology; D014693:Ventricular Fibrillation / Q000209:etiology* / Q000503:physiopathology