Abstract | OBJECTIVES: METHODS:
Cardiac failure was induced by doxorubicin injection (1-1.25 mg.kg-1 twice weekly for 8 weeks, n = 16) or coronary ligation (n = 12), with 12 controls. Cardiac failure was defined by an echocardiographic ejection fraction < or = 0.40. Arrhythmia susceptibility was assessed by programmed ventricular stimulation and fibrillation threshold measurement during Langendorff and during working heart perfusion under baseline conditions and at maximum tolerated preload and afterload. Monophasic action potential duration, dispersion of refractoriness, conduction time and effective refractory period were measured at each level of load. RESULTS: During unloaded (Langendorff) perfusion, there was a low incidence of arrhythmia induction in all hearts. Increasing load did not alter arrhythmogenesis significantly in normal hearts, but led to increases in arrhythmia inducibility and falls in fibrillation threshold which were significantly greater in failing than in non-failing hearts. Monophasic action potential duration was significantly (P < 0.05) shorter in failing than in non-failing hearts in the doxorubicin-treated [mean (s.e. m.) 140(2) vs. 147(2) ms] and post- infarction groups [146(2) vs. 154 (3) ms] during working heart perfusion. The shortening in action potential duration and effective refractory period during increased preload tended to be greater in failing than in non-failing hearts. There were no changes in conduction times in response to changes in loading. CONCLUSIONS: The inducibility of ventricular arrhythmias is greater in failing than in non-failing hearts and is further enhanced by increases in preload. Shortening of repolarization and refractoriness due to increased preload may contribute to the increased risk of ventricular tachyarrhythmias and sudden death in cardiac failure.
|
Authors | M P Pye, S M Cobbe |
Journal | Cardiovascular research
(Cardiovasc Res)
Vol. 32
Issue 2
Pg. 248-57
(Aug 1996)
ISSN: 0008-6363 [Print] England |
PMID | 8796111
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
|
Topics |
- Action Potentials
(physiology)
- Animals
- Arrhythmias, Cardiac
(diagnostic imaging, etiology, physiopathology)
- Doxorubicin
- Echocardiography
- Heart
(physiopathology)
- Heart Failure
(complications, diagnostic imaging, physiopathology)
- Male
- Models, Cardiovascular
- Myocardial Infarction
(complications, diagnostic imaging, physiopathology)
- Perfusion
- Rabbits
|