Key Points
- To determine whether and through which electrophysiological mechanisms a proarrhythmic substrate develops in a rat model of pulmonary hypertension and right ventricular hypertrophy.
- Rats received a single injection of monocrotaline (60 mg/kg) to induce pulmonary hypertension or saline as controls, followed by assessment 22 to 26 days post-treatment.
- Myocardial ion channel mRNA expression was measured via real-time RT-PCR, and monophasic action potential duration (MAPD) and restitution kinetics were evaluated in isolated Langendorff-perfused hearts under burst pacing.
- Computer simulations incorporating ion channel gene expression profiles were performed to model observed alterations in MAPD and electrical restitution.
- Sustained ventricular tachycardia or fibrillation was induced in 83% of monocrotaline-treated hearts compared with 14% of control hearts.
- Monocrotaline-treated hearts exhibited reduced potassium channel mRNA expression, prolonged MAPD predominantly in the right ventricle, and steeper right ventricular electrical restitution curves compared to controls.
- Right-to-left ventricular dispersion of MAPD was significantly amplified in a stimulation frequency-dependent manner in monocrotaline hearts.
Structured PICO
PPopulationRat model of right ventricular hypertension and hypertrophy
IInterventionMonocrotaline (MCT; 60 mg/kg) injection to induce pulmonary artery hypertension
CComparatorSaline injection (CON)
OOutcomeDevelopment of sustained ventricular tachycardias/fibrillation and electrophysiological changes (monophasic action potential duration and restitution)surrogate
In a rat model, monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy create a proarrhythmic substrate characterized by steeper RV electrical restitution and rate-dependent RV-LV action potential duration dispersion.