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Delayed afterdepolarizations and triggered arrhythmias in hypertrophic cardiomyopathic hearts
1Department of Pediatrics, College of Medicine, University of Iowa, Iowa City.
Insights
Hypertrophic cardiomyopathy increases sudden cardiac death risk, potentially due to ventricular tachyarrhythmia. This study found increased delayed afterdepolarizations and triggered activity in affected hearts, suggesting a mechanism for arrhythmia development.
Area of Science:
- Cardiology
- Molecular Biology
- Physiology
Background:
- Hypertrophic cardiomyopathy (HCM) is linked to sudden cardiac death.
- Ventricular tachyarrhythmia is a suspected mechanism for this risk.
- The electrophysiological basis of arrhythmia in HCM requires further investigation.
Purpose of the Study:
- To investigate the propensity for delayed afterdepolarizations (DADs) and triggered activity in hypertrophic cardiomyopathy.
- To compare electrophysiological properties between hereditary HCM hamsters (BIO 14.6) and controls (BIO RB).
- To explore the role of extracellular calcium and protein kinase C (PKC) in modulating these phenomena.
Main Methods:
- Utilized standard microelectrode techniques on isolated ventricular myocardium.
- Induced DADs and triggered activity using burst pacing and isoproterenol.
- Manipulated extracellular calcium concentrations and applied a PKC-activating phorbol ester.
Main Results:
- Ventricular myocardium from BIO 14.6 hamsters showed inducible DADs and triggered activity more readily than controls.
- Isoproterenol significantly enhanced DADs and triggered activity in BIO 14.6 preparations.
- Increased extracellular calcium potentiated DAD induction in both groups, particularly in BIO 14.6.
- PKC activation suppressed beta-adrenergic-induced triggered activity in HCM myocardium.
Conclusions:
- Hereditary hypertrophic cardiomyopathy in BIO 14.6 hamsters exhibits an increased susceptibility to DADs and triggered activity.
- These electrophysiological abnormalities may contribute to the arrhythmogenic substrate in HCM.
- Extracellular calcium and PKC signaling represent potential modulators of arrhythmia risk in HCM.
Abstract:
Hypertrophic cardiomyopathy is known to be associated with increased risk of sudden cardiac death. The mechanism is unknown but ventricular tachyarrhythmia is believed to be a major contributing cause. Using standard microelectrode techniques, we examined the propensity of delayed afterdepolarizations (DADs) and triggered activity development in isolated ventricular myocardium from Syrian hamsters with hereditary hypertrophic cardiomyopathy (BIO 14.6) and control hamsters (BIO RB). Induction of DAD was facilitated by burst pacing (15-beat trains with decremental cycle lengths) and with isoproterenol (2 x 10(-7) mol/L). Under baseline conditions with Tyrode's solution containing 2.0 mmol/L CaCl2, no DADs were inducible in eight preparations of myocardium from normal hamsters by burst pacing with or without isoproterenol. In contrast, 2 out of 6 preparations of ventricular myocardium from BIO 14.6 hamsters had inducible DADs by burst pacing alone, and 5 out of 6 preparations had inducible DADs or triggered activity in the presence of isoproterenol (p < 0.05 compared with control). Increasing the extracellular Ca++ to 4.0 mmol/L resulted in enhancement of inducible DADs: in 2 out of 8 preparations with pacing alone, in an additional 2 preparations with isoproterenol in control myocardium, and in 5 out of 6 preparations of BIO 14.6 by burst pacing alone (p < 0.05 compared with control). Exposure to the protein kinase C (PKC)-activating phorbol ester phorbol 12-myristate 13-acetate resulted in suppression of the beta-adrenergic-induced triggered activity in hypertrophic cardiomyopathic preparations.(ABSTRACT TRUNCATED AT 250 WORDS)