Spontaneous Ventricular Fibrillation in Right Ventricular Failure Secondary to Chronic Pulmonary Hypertension

S. Umar, J.-H. Lee, E. de Lange, A. Iorga, R. Partow-Navid, A. Bapat, A. van der Laarse, R. Saggar, D.L. Ypey, H.S. Karagueuzian, M. Eghbali

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Abstract

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.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
Original languageEnglish
Pages (from-to)181-190
Number of pages10
JournalCirculation-Arrhythmia and Electrophysiology
Volume5
DOIs
Publication statusPublished - 2012

Cite this

Umar, S., Lee, J-H., Lange, E. D., Iorga, A., Partow-Navid, R., Bapat, A., van der Laarse, A., Saggar, R., Ypey, D. L., Karagueuzian, H. S., & Eghbali, M. (2012). Spontaneous Ventricular Fibrillation in Right Ventricular Failure Secondary to Chronic Pulmonary Hypertension. Circulation-Arrhythmia and Electrophysiology, 5, 181-190. https://doi.org/10.1161/CIRCEP.111.967265