Document Detail

Arrhythmogenic substrate in hearts of rats with monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy.
MedLine Citation:
PMID:  21398591     Owner:  NLM     Status:  MEDLINE    
Mechanisms associated with right ventricular (RV) hypertension and arrhythmias are less understood than those in the left ventricle (LV). The aim of our study was to investigate whether and by what mechanisms a proarrhythmic substrate exists in a rat model of RV hypertension and hypertrophy. Rats were injected with monocrotaline (MCT; 60 mg/kg) to induce pulmonary artery hypertension or with saline (CON). Myocardial levels of mRNA for genes expressing ion channels were measured by real-time RT-PCR. Monophasic action potential duration (MAPD) was recorded in isolated Langendorff-perfused hearts. MAPD restitution was measured, and arrhythmias were induced by burst stimulation. Twenty-two to twenty-six days after treatment, MCT animals had RV hypertension, hypertrophy, and decreased ejection fractions compared with CON. A greater proportion of MCT hearts developed sustained ventricular tachycardias/fibrillation (0.83 MCT vs. 0.14 CON). MAPD was prolonged in RV and less so in the LV of MCT hearts. There were decreased levels of mRNA for K(+) channels. Restitution curves of MCT RV were steeper than CON RV or either LV. Dispersion of MAPD was greater in MCT hearts and was dependent on stimulation frequency. Computer simulations based on ion channel gene expression closely predicted experimental changes in MAPD and restitution. We have identified a proarrhythmic substrate in the hearts of MCT-treated rats. We conclude that steeper RV electrical restitution and rate-dependant RV-LV action potential duration dispersion may be contributing mechanisms and be implicated in the generation of arrhythmias associated with in RV hypertension and hypertrophy.
David Benoist; Rachel Stones; Mark Drinkhill; Olivier Bernus; Ed White
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-03-11
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  300     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-02     Completed Date:  2011-08-23     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H2230-7     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Action Potentials / physiology
Arrhythmias, Cardiac / physiopathology*
Calcium Channels / physiology
Computer Simulation
Disease Models, Animal
Electric Stimulation
Hypertension, Pulmonary / chemically induced*,  physiopathology*
Hypertrophy, Right Ventricular / chemically induced*,  physiopathology*
Monocrotaline / adverse effects*
Potassium Channels / physiology
Rats, Wistar
Stroke Volume / physiology
Tachycardia, Ventricular / physiopathology
Grant Support
G0900524//Medical Research Council; G900524//Medical Research Council; PG/08/027/24774//British Heart Foundation
Reg. No./Substance:
0/Calcium Channels; 0/Potassium Channels; 73077K8HYV/Monocrotaline

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Postinfarction healing dynamics in the mechanically unloaded rat left ventricle.
Next Document:  Gender differences affect blood flow recovery in a mouse model of hindlimb ischemia.