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Updated: Jul 30, 2026
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Benefits of Cardiac Resynchronization Therapy in an Asynchronous Heart Failure Model Induced by Left Bundle Branch Ablation and Rapid Pacing
Published on: December 11, 2017
Mechanisms whereby rapid RV pacing causes LV dysfunction: perfusion-contraction matching and NO
L A Nikolaidis1, T Hentosz, A Doverspike
1Department of Medicine, Allegheny General Hospital, MCP-Hahnemann University School of Medicine, Pittsburgh, Pennsylvania 15212, USA.
American Journal of Physiology. Heart and Circulatory Physiology
|November 16, 2001
Summary
Incessant tachycardia causes heart dysfunction by initially matching blood flow to metabolic needs, but later leads to impaired nitric oxide production and contractility decline, resulting in heart failure.
Area of Science:
- Cardiovascular Physiology
- Cardiac Metabolism
- Heart Failure Pathophysiology
Background:
- Incessant tachycardia is a known cause of dilated cardiomyopathy, but the underlying mechanisms remain unclear.
- Understanding the relationship between heart rate, contractility, and metabolic demands is crucial for explaining tachycardia-induced heart dysfunction.
Purpose of the Study:
- To investigate the hypothesis that excessive chronotropic demands necessitate compensatory reductions in myocardial contractility to balance metabolic requirements.
- To elucidate the mechanisms linking tachycardia to cardiac dysfunction, focusing on hemodynamic, metabolic, and nitric oxide production alterations.
Main Methods:
- Conscious dogs underwent rapid right ventricular pacing for 4 weeks.
- Measurements included hemodynamics, coronary blood flow (CBF), myocardial oxygen consumption (MVO2), nitric oxide (NO) production, and substrate utilization.
- Left ventricular contractility was assessed using the first derivative of pressure over end-diastolic diameter [(LV dP/dt)/LVEDD].
Main Results:
- Early pacing (6h-72h) showed decreased HR-adjusted CBF, MVO2, and contractility, indicating flow-metabolism-function coupling.
- Later pacing (28 days) revealed increased CBF/beat and MVO2/beat, but a significant decline in contractility, signifying flow-function mismatch.
- The late phase was characterized by decreased cardiac NO production, reduced fatty acid utilization, and increased glycogen content and lactate uptake.
Conclusions:
- Incessant tachycardia induces contractile, metabolic, and flow abnormalities that initially match function with supply but progress to left ventricular dysfunction.
- The transition to heart failure is associated with a shift to flow-function mismatch and impaired myocardial nitric oxide production.
- These findings highlight the complex interplay of factors contributing to tachycardia-induced cardiomyopathy.
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